Aloe Vera Alimento Funcional 2011

December 31, 2009
2:5
FSN
BFSN_A_354613
Critical Reviews in Food Science and Nutrition, 50:122 (2010)

C Taylor and Francis Group, LLC
Copyright
ISSN: 1040-8398
DOI: 10.1080/10408390802544454
Aloe vera as a Functional Ingredient

in Foods
1
2 and
ELENA RODRIGUEZ
RODRIGUEZ,
JACINTO DARIAS MARTIN,
1
CARLOS DIAZ
ROMERO
1
Department of Analytical Chemistry, Food Science and Nutrition, University of La Laguna, La Laguna, Santa Cruz de
Tenerife, Spain
2
Department of Chemical Engineering and Pharmaceutical Technology, University of La Laguna, La Laguna, Santa Cruz de
Tenerife, Spain
10
15
20
Q1
Q2
The main scientific discoveries on Aloe vera published mainly in the last three decades are presented in this work. After
describing Aloe from a botanical point of view, the papers related with the chemical composition of different parts of the
leaf of Aloe, particularly those in which the gel is described and are presented in a synthetic manner. The chemical analyses
reveal that Aloe gel contains mannose polymers with some glucose and other sugars, among which the most important
is Acemannan. Besides these, other components such as glycoproteins, enzymes, amino acids, vitamins, and minerals are
described. The different factors also affecting the chemical composition of the gel, such as species and variety, climatic and
soil conditions, cultivation methods, processing and preservation, are enumerated and discussed.
On the other hand, the main therapeutic applications have been revised and the possible damaging effects of Aloe are also
commented upon. A special emphasis is placed on the biologically active compounds or groups of compounds responsible
for the therapeutic applications and which are their action mechanisms. The paper concludes that more research is needed
to confirm the therapeutic and beneficial effects and to definitively clarify the myth surrounding Aloe vera. A general view
on the problem of the commercialization and establishment of the quality and safety of Aloe products in the food industry
has been offered here. The main points and European regulations that need to be considered regarding the quality control of
prepared Aloe products are presented in this paper.
INTRODUCTION
(Reynolds, 1985). This plant is however related to the Liliaceae

family, and therefore also related to plants such as onion, garlic,
and asparagus, which are known to have medicinal properties 40
(Lawless and Allen, 2000). Most of these plants originated in
the dry regions of Africa, Asia, and Southern Europe, especially
in the Mediterranean regions (Urch, 1999). Due to the numerous beneficial effects attributed to Aloe gel, its production is
an emerging industry for making cosmetics, functional food, 45
and drugs and due to its medicinal properties it is being cultivated in other areas with different climatic conditions. Mexico is
the main producer of Aloe, followed by Latin America, China,
Thailand, and the United States (Rodriguez, 2004). Aloe plants
range in height from a few cm to 23 m or more. The leaves 50
of some of the species are very large and are lance shaped with
Q3
jagged edges (Urch, 1999).
There are at least four species of the over 360 known ones
that have medicinal propertiesAloe arborescens Miller; Aloe
perryi Baker; Aloe ferox Miller o Aloe capensis; and Aloe bar- 55
badensis Miller, also known as Aloe vera Linne o Aloe vulgaris
Lamark (Atherton, 1998; Urch, 1999). This last specie is the
most popular one and is also the most widely cultivated. Aloe
Food has drastically changed in the last thirty years. The

main tendency is towards the production of higher amounts of
foods of better quality and at a lower price. The design of new
foods is included within these new tendencies in the world of
food. In accordance with the current legislation, new foods or
new food ingredients are the ones that had not been consumed
30 in large amounts in the European Community before May 15th
1997 (Reglamento CE 258/1997). Aloe vera is one of the many
food products that can be considered as new food or new food
ingredient.
From times immemorial Aloe has been used in an empiric
35 way for the treatment of diverse disorders and ailments. Many
authors have considered Aloe to be a member of the Liliaceae
family, but it comes from a family of its own called Aloaceae
25
Address correspondence to Carlos Daz Romero, Department of Analytical Chemistry, Food Science and Nutrition, University of La Laguna, Avda.
Astrofsico Francisco Sanchez s/n, La Laguna, Santa Cruz de Tenerife. 38201.
Spain, Telephone:+34 922 318049, Fax:+34 922 318003. E-mail: cdiaz@ull.es
December 31, 2009
2:5
FSN
BFSN_A_354613
E. R. RODRIGUEZ ET AL.
vera and other species of Aloe are succulent and xerophyte

plants that are adapted to living in areas with little water. These
plants possess extensive water storage tissue in their leaves, the
part of the plant which is used for its therapeutic properties.
The aim of this paper is to provide general and synthetic
information regarding Aloe vera and its beneficial properties,
65 emphasizing its use in the food industry as a new or functional
food. The main scientific papers published in the last thirty years
have been presented here. Besides, some previously published
papers are also included for their relevance and interest. This review addresses the following aspects:1) Chemical composition
70 of the exudate and gel of Aloe; 2) Medical uses and applications;
3) Biologically active compounds and therapeutic properties; 4)
Quality control and legal aspects; and 5) Concluding remarks.
60
in particular of polysaccharides. Therefore, different products

with a different chemical composition can be obtained in the
function of the processing technique used to obtain the gel. This
explains, at least in part, the differences observed by different
authors in the chemical composition of the gel, mainly referring 115
to the type of polysaccharides (Ni et al., 2004).
In view of the complexities inherent in Aloe pharmacology,
it is convenient to be as rigorous as possible when separating
both fractions, and once the biological properties of each one of
them are established in an independent way, one can combine 120
both fractions in later investigations. Therefore, the chemical
compounds in the leaf of Aloe can be divided into two groups:
Exudate Compounds
CHEMICAL COMPOSITION OF THE EXUDATE
AND GEL OF ALOE
75
80
85
90
95
100
105
110
Most of the whole leaf is water and, there are more than
200 chemical substances in the dry matter constituting the
leaf. Therefore, the concentration of these components is relatively low (Luta and McAnalley, 2005). The largest component (60%) in the dry matter, are the carbohydrates (soluble
sugars and complex polysaccharides). The composition of these
carbohydrates differs depending on the part of the leaf considered (Femenia et al., 1999; Ni et al., 2004). Proteins and lipids
account for about 68% and 25% of the dry matter, respectively with larger quantities being observed in the gel than in
the exudate of the plant (Femenia et al., 1999). Other minority components that may be biologically active include phenolic
compounds, organic acids and amino acids, certain vitamins and
minerals, and volatile compounds (Luta and McAnalley, 2005).
Some confusion still surrounds the exudates and gel of the
leaf, both of which have largely been used for various reasons
in popular medicine. Nevertheless, many authors have clearly
distinguished the two parts (Capasso et al., 1998; Femenia et
al., 1999; McKeown, 1987), and others have described the separation of the gel in some detail (Agarwala, 1997; McAnalley,
1988, 1990; Spoerke and Elkins, 1980). There has been great
controversy about the relative effectiveness of the colorless and
colored derivatives of the gel (Agarwala, 1997; Danof, 1987).
The distinction is sometimes difficult because some chemical
components of the exudate can be introduced into the gel during its separation. In some studies the extracts of the complete
leaf have also been used. This can create confusion about the
medical properties attributable to certain components, since the
determined medical synergistic effects could not be observed,
if both fractions were kept separately, or on the contrary, undesirable effects could occur as a result of the presence of some
components of the exudate in the gel. Three structural components 1) cell walls and cell membranes; 2) microparticles of
subcelular organelles; and 3) viscous liquid gel, have been separated from the pulp of the A. vera leaf (Ni et al., 2004). Each of
these three components has a different chemical composition,
The yellow exudate is rich in anthraquinones which are

phenolic compounds which have been thoroughly revised
(Reynolds, 1985). Figure 1 shows the main phenolic compounds
isolated from the Aloe exudates. For centuries they have been
used for their purgative effects, and as a bitter agent in the preparation of alcoholic drinks (Saccù et al., 2001). Anthraquinones
are formed by oxidation of low molecular weight components
such as aloin, which is a glycoside derivative of aloe-emodin.
Exudates of around 300 species of Aloe have been examined by liquid chromatography and about 80 chemical compounds have been separated and identified in this study. A total
of 13 phenolic compounds have been identified and quantified by high performance liquid chromatography (HPLC) in
reverse phase with UV detectionAloesin, 8-C-glucosyl-7-Omethyl(S)-aloesol, neoaloesin A, 8-O-methyl-7-hydroxyaloin A
and B, 10-hydroxyaloin A, isoaloeresin D, aloin A and B, aloeresin E, and aloe-emodin from A. barbadensis; and aloenin,
aloenin B, 10-hydroxyaloin A, aloin A and B and aloe-emodin
from A. arborescens (Park et al., 1998). Aloe ferox produces
Figure 1 Structures of Aloin A and B, Aloe-emodin, Aloenin, Aloesin, and

Aloeresin A.
125
130
135
140
December 31, 2009
2:5
FSN
BFSN_A_354613
ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS
145
150
155
160
165
170
175
Q4 180
185
greater quantities of bitter sap and other medicinal components

than the more widely known Aloe vera (Van Wyk et al., 1997).
A simple and fast reversed-phase HPLC method for the determination of aloesin, aloeresin A, and antraquinone in Aloe ferox
and Aloe-related products was recently developed and validated
(Zahn et al., 2008). Saccù et al. (2001) have characterized several commercial exudates of Aloe by means of HPLC in reverse
phase with a UV detector, and gas chromatography (GC) coupled to a mass spectrometry (MS) detector using the headspace
in the column technique, for the determination of the phenolic
constituent and of the volatile fraction, respectively. This makes
the characterization of the commercial products possible. The
photochemical profile of A. secundiflora has been studied using the HPLC-MS finding a mixture of phenolic compounds.
Among them the anthrone contents stand out (aloenin, aloenin
B, aloin B, and other aloin derivates), and so also the chromones
and phenylpyrones (Rebecca et al., 2003). The aloin contents
were examined by HPLC in six species of Aloe, and they were
related with the structure of the leaf. The largest aloin quantity
was observed in A. arborescens, and the levels were low or very
low in A. vera and A. saponaria, respectively (Li et al., 2003). It
was also found that by applying fluorescence microscopy, aloin
was stored in the large parenchymatous cells of vascular bundles, the vascular bundle sheath, and the aquiferous tissue sheath
(Li et al., 2003). Aloin occurs naturally as a mixture of two diasteroisomers, aloin A and B, which have been separated by
high-speed countercurrent chromatography (Cao et al., 2007).
An attempt was made by Viljoen et al. (2001) at a taxonomic
classification of the function of the presence of anthrone isomers
such as aloin A and B, together with aloinoside isomers and microdontin A and B. These phenolic compounds such as the aloins
A and B are very unstable in aqueous solutions, in particular in
alkaline conditions (Zonta et al., 1995). This may explain why
these compounds are not detected in prepared drinks with an
Aloe base (Zonta et al., 1995).
Besides the phenolic compounds the exudate of the leaf contains small quantities of polysaccharides and free sugars, especially glucose, volatile and aliphatic compounds (Rebecca et al.,
2003; Saccù et al., 2001). Two glyoxalases I and II have also
been isolated from the outer green rind of A. vera leaves, which
were compared with reported animal and other plant glyoxalases
(Norton et al., 1990).
Gel Compounds
Most of the authors attribute the beneficial effects of the plant

to the gel. The reasons justifying the effectiveness of the gel are
often uncertain perhaps because in fact there are several healing
activities intervening together (Capasso et al., 1998). On the
190 other hand, these therapeutic properties attributed to the gel are
disproportionate in relation to the contents of the substances that
they contain. This could be explained because the cocktail of
chemical substances, or constituent active principles, act synergically in the prevention and cure of numerous disorders and
illnesses. It is essential to understand the chemical composition

of Aloe gel better to be able to discover the mechanisms which
provide it with beneficial properties for health.
Few species of Aloe have been examined to establish the
characteristics of the gel. Although A. vera gel is the only one
that has been marketed, there is the possibility of discovering
useful and therapeutic properties among the more than 360 wellknown species (Newton, 1987). The chemical composition of
the mucilage isolated from the raw leaf without preservation
processes is presented in Table 1. Aloe gel contains between
98.5 and 99.5% of water with a pH of between 45 (Femenia
et al., 1999; Gjerstad, 1971), therefore, the caloric value of the A.
vera gel is very low. So, the consumption of one serving (200
ml) of gel contributes less than 5 kcal. The pH of the previously
filtrated A. vera gel had a relatively low range, between 4 and 5
(Eshun and He, 2004). Approximately 80% of the solids in the
gel are water-soluble compounds (Luta and McAnalley, 2005).
195
200
205
210
Carbohydrate Fraction
This major fraction in the Aloe gel is composed of free sugars, soluble polysaccharides, and fibers. A study on the rheology of the gel suggests that the glucomannans of the Aloe gel
are uncommon in most other species of plants; however, they
are related to some human corporal fluids (Yaron, 1991). The
polysaccharides from the species A. arborescens, A. vahombe
(sic.), A. plicatilis (L.) Mill, and A. barbadensis (Grindlay and
Reynolds, 1986), and A. saponaria and A. vanbalenii Pillans
(Gowda, 1980), had been extracted and characterized till 1986.
Later, A. ferox was added to this list (Mabusela et al., 1990). In
this specie, the arabinogalactans and rhamnogalacturonans were
apparent, whereas glucomannans, common in the other species
of Aloe, were less apparent in A. ferox.
There has been little agreement on the composition of these
polysaccharides in the gel which could probably be related to
the different separation, and the determination methods used.
Besides, it is possible that these differences are due to the soil
composition and climatic conditions, the cultivation method,
and other characteristics. In the 1970s, Ovodova et al. (1975)
reported that the presence of uronic acid yields galacturonic
acid and oligosaccharides, upon fermentative hydrolysis with
pectinase. However, Segal et al. (1968) have not found uronic
acids in the analytical investigation. Gjerstad (1971) indicated
that the carbohydrates of the A. vera gel were composed of glucose and a polyuronide, consisting of a high molecular weight
glucose-mannose polyose (molecular weight up to about 275
KDa). The hexuronic acids detected produce glucose and mannose in its hydrolysis, as well as trace amounts of galactose,
arabinose, and xilose. Polysaccharides present in the Aloe gel
are lineal polymers with no branching with different proportions of single sugars, which contain -glycosidic 14 linkages which can be separated by precipitation with alcohol
(Gowda et al., 1979; Gowda, 1980; Manna and McAnalley,
1993; Paulsen et al., 1978). However, there are polymers of
other hexoses, like in the case of A. ferox, in which galactose and
215
220
225
230
235
240
245
December 31, 2009
2:5
FSN
BFSN_A_354613
4
Table 1
Chemical composition of Aloe vera gel
I NUTRITIVE COMPOUNDS
Water/moisture
Carbohydrates
Soluble polysaccharides
Free monosaccharides
Nitrogen fraction
Aminoacids
Glycoproteins
Enzymes
Vitamins
Minerals and trace elements
REFERENCIAS
98.599.5%
pH = 45
0.25% (2550% of dry matter)
Glucomannans (acetylated partially) Acemannan
93% Mannose (3% Glucose, 3% Galactose) 95%
Free glucose (Fructose, Galactose)
N2 protein (0,013%)
18 (7 of the 8 essential; 20% Arg)
Lectins with hemoaglutination activity (A.
arborescens)
Aloctin A (12% of carbohydrates; PM=18KDa)
Aloctin B (50% of carbohydrates; PM=24KDa)
Bradykinase, Carboxypeptidase, Catalase, SOD,
GSH-Px, Peroxidase
Ascorbic acid
Complex B: Thiamin, riboflavin, niacin, folic acid
Carotenoids, tocopherols
2425% of dry matter
Minerals and electrolytes K, Cl (Na), Ca, Mg, P
Trace elements Fe, Cu, Zn, Mn, Al, Se, Cr
II) NON-NUTRITIVE COMPOUNDS

Organic acids
Phenolic compounds
Phytosterols
Other compounds
250
255
260
265
Atherton (1998); Femenia et al. (1999); Gjerstad

(1971); Waller et al. (1978)
Chow et al. (2005); Femenia et al. (1999); Gowda
(1979); Leung et al. (2004); Liu et al. (2007);
Mandal, and Das (1980); Manna, and McAnalley
(1993); McAnalley (1990); Meadows (1980); Ni
et al. (2004); Paez et al. (2000); Paulsen et al.
(1978); Pugh et al. (2001); Talmadge et al. (2004);
Waller et al. (1978)
Akev, and Can (1999); Atherton (1998);
Bautista-Perez et al. (2004); Beppu et al. (2006a);
Choi et al. (2001); Esteban et al. (2000); Fujita
(1976, 1979); McKeown (1983); Meadows (1980);
Ni et al. (2004); Reynolds, and Dweck (1999);
Sabeh (1993, 1996)
Atherton (1998); Lawless, and Allan (2000)
Atherton (1998); Femenia et al. (1999); Li et al.

(2004); Ni et al. (2004); Rajasekaran et al. (2005);
Sahito et al. (2003); Wang, and Strong (1993);
Yamaguchi et al. (1993); Yang et al. (2004)
REFERENCES
Salycilic acid
Malic acid
Lactic, acetic, succinic acids
Trace of anthraquinones Aloin A y B, Aloe-emodin,
Aloenin, Aloesin, Aloeresin,. . .
-sitosterol, campesterol.
Alyphatics hydrocarbons/esters long chain; volatile
compounds (acids, aldehydes, ketones,. . . .)
galacturonic acid polymers are frequently found (Reynolds and

Dweck, 1999).
The polysaccharides of the Aloe gel can be acylated, partially
acylated, or not acylated. Meadows (1980) indicated that at least
four different and partially acetylated glucomannans were responsible for producing the thick stringy mucilage characteristic of the raw Aloe gel. A series of highly purified galacturonate
polysaccharides have recently been extracted from the A. vera
plant and analyzed in terms of chemical composition and molecular weight (McConaughy et al., 2008). This A. vera polysaccharide has been found to exist as a high molecular weight species
and to possess a unique chemical composition, including a high
galacturonic acid content and low degree of methyl ester substitution. Other investigators (Esua and Rauwald, 2006) have
isolated three malic acid acylated polysaccharides Veracylglucans A, B, and C from A. vera gel.
According to the observations reported by different authors,
especially for the case of A. barbadensis, there are considerable differences in the structures of the isolated polysaccharides (Reynolds and Dweck, 1999). These polysaccharides are
mainly composed of mannose units that are randomly substituted by glucose. Minority amounts of xilose, rhamnose, galac-
Atherton (1998); Loots et al. (2007); Ni et al. (2004);

Paez et al. (2000)
Loots et al. (2007); Ni et al. (2004); Okamura et al.
(1996); Park et al. (1998); Perez et al. (2007)
Atherton (1998); Moon et al. (1999)
Atherton (1998); Loots et al. (2007)
tose, arabinose, mucose, or uronic acids have also been identified (Mandal and Das, 1980; tHart et al., 1989). It is not well
known, whether the presence of these sugars is an integral part of
the structure of the hydrocarbonated fraction, or whether these
are a consequence of the presence of polluting carbohydrates.
The extracted majority carbohydrate of the Aloe gel is generically denominated Acemannan (Manna and McAnalley, 1993),
whose important therapeutic properties are attributed (Zhang
and Tizard, 1996). The Acemannan or CarrysinTM , available
commercially, is an acetylated polymer of mannose that is isolated from the A. vera gel (McDaniel et al., 1987). After separating the Acemannan by chromatography, it was proven that
the polysaccharide was mainly composed of mannose 93%, glucose, and galactose in 3% each one and less than 1% of arabinose
(McAnalley, 1990; Talmadge et al., 2004). Acemannan may be
related with the Aloe mannan which was isolated somewhat
earlier from A. arborescens (Yagi et al., 1977). Femenia et al.
(1999) have chemically characterized the gel, pulp, and skin of
the leaves of A. vera. The extraction of fractions of lyophilized
Aloe indicates that the carbohydrates represent more than 80%.
A sequential extraction of the present polysaccharides in Aloe
revealed that there were two polymers containinig mannose. A
270
275
280
285
290
December 31, 2009
2:5
FSN
BFSN_A_354613
295
300
305
310
315
320
325
330
storage polysaccharide was found in the protoplast of parenchymatous cells in the pulp of the Aloe gel. Mannose and glucose (constituent of cellulose) are the main components of the
polysaccharides in all the derivates, and pectic polysaccharides
were also detected.
Chow et al. (2005) have recently investigated the structure
of the soluble fraction of polysaccharides of A. vera isolated by
precipitation with alcohol. This soluble fraction of polysaccharides was hydrolyzed with acid at high temperature, producing
a mixture of oligosaccharides and an acid resistant fraction,
accounting for nearly 37% of the bulk material. The acid resistant fraction contained arabinose (18%), galactose (18%),
glucose (9%), xylose (9%), and galacturonic acid (5%). This
acid resistant fraction had a different chemical composition to
that of the water-soluble polysaccharides, which was composed
of 84%, 6%, and 4% mannose, glucose, and galactose respectively (Chow et al., 2005). Thus, the presence of an acid resistant fraction with a carbohydrate composition inconsistent
with this majority structure suggests that there are other different substructures in the soluble polysaccharides of Aloe.
These authors (Chow et al., 2005) have carried out analyses
of the structure for nuclear magnetic resonance (NMR). This
structure, after treatments with endo -mannanase, has more
than enough purified oligosaccharides, confirming the presence
of Glc1-4Man1,4Man, and Man1,4[Gal1,6]Man connections as well as di-, tri-, and tetrasaccharides of 1,4-linked
mannose. Mannose molecules, with random substitutions of glucose, should form the chemical structure. There are also linkages
1-6 between mannose and galactose. Three purified polysaccharide fractions were prepared from A. vera gel by membrane
fractionation and gel filtration HPLC. Variable contents of mannose and variable molecular weights were found in these three
fractions. It was observed that the biological response of Aloe
polysaccharide fraction increases as the mannose content and
the molecular weight of the polysaccharide fraction increase
(Leung et al., 2004).
The free monosaccharides represent approximately 25% of
the dry gel, with glucose accounting for 95% of the soluble
sugars (Femenia et al., 1999). Other authors (Paez et al., 2000)
indicated the presence of other free sugars like fructose and
galactose, in significant amounts, although always smaller than
the amount of glucose.
species of Aloe. This disrupts the oligomeric proteins and the

resulting polypeptides are ordered according to their molecular
weight (Winters and Yang, 1996). It was observed that A. vera,
A. arborescens, and A. saponaria had a total of 12, 9, and 12
major polypeptides, respectively. Five major polypeptides, with
molecular weights of 15, 46, 6566, 71, and 7677 KDa, was
common for these three species.
The presence of glycoproteins with biological or enzymatic
activity has been described. A fraction of A. arborescens gel
was shown to be a glycoprotein, appearing like a single electrophoretic band (Yagi et al., 1986), while another two glycoproteins fractions were separated by differential precipitation
(Kodym, 1991). A haemagglutinating activity, typical of lectins,
was found in fractions of A. vera, A. arborescens, and A. chinensis (sic) (Winters, 1993). Two proteins were isolated, Aloctin
A and Aloctin B, from A. arborescens (Akev and Can, 1999;
Saito, 1993; Suzuki et al., 1979). Aloctin A has a molecular
weight of 18 KDa and it is made up of two subunits of 7.5
and 10.5 KDa with a carbohydrate content of 18%. Aloctin B
was 24 KDa, with two subunits of 12 KDa each and a carbohydrate content of 50%. A glycoprotein denominated as ATF191,
was subsequently isolated from the same species (Yoshimoto
et al., 1987), while later another lectin, of molecular weight of
35 KDa, was obtained from the outer layers of the leaf (Koike
et al., 1995). A glycoprotein (Pg21-2b) with cell proliferationpromoting activity was isolated from the A. vera gel (Yagi et al.,
1997), which had a molecular weight of 29 KDa and consisted
of two subunits. Other protein fractions showed growth inhibiting activity; however, this could be associated with phenolic
contaminants.
Meadows (1980) claimed that at least 6 enzymes exist in the
Aloe gelBradykinase, cellulase, carboxypeptidase, catalase,
amylase, and oxidase. The bradykinase activity in the Aloe extract has subsequently been studied by many authors (BautistaPerez et al., 2004; Fujita et al., 1976; Yagi et al., 1982). Extracts
of Aloe have been associated with enzymatic activities of diverse enzymes such as superoxide dismutase (SOD) (Sabeh et
al., 1996), glutathione peroxidase (GSH-Px) (Sabeh et al., 1993),
and other peroxidases (Esteban et al., 2000). The SOD activity
occurred in seven previously separated electrophoretic bands,
two of which were Mn dependent and the rest Cu-Zn dependent
(Sabeh et al., 1996). GSH-Px consists of four identical subunits;
and contains one atom of Se for each subunit, in a similar way
to most GSH-Px of animal origin (Sabeh et al., 1993).
345
350
355
360
365
370
375
380
385
Nitrogen Fraction
Most of the suitable preparations of polysaccharides contain very little or no nitrogen, hence the protein content of
a lyophilized commercial product of the gel of Aloe, determined by the method Kjeldahl, was very low, around 0.013%
(McKeown, 1983). On the other hand, Waller et al. (1978) ana340 lyzed extracts obtained by maceration of whole leaves in acetone
and detected 17 amino acids in a free state, among which arginine has the highest content representing approximately 20%
of total amino acids. More recently, the polypeptide composition of proteins has been determined in the gel of various
335
Other Components
A wide variety of more or less simple compounds have been 390
described in Aloe gel (Grindlay and Reynolds, 1986). However,
there is always the problem of achieving a complete separation of the gel from the plant exudate components (Agarwala,
1997). Phenolic compounds can be included in the group of minority compounds in Aloe gel (Park et al., 1998). The phenolic 395
compound concentrations in Aloe gel are 1.253 times lower
than those obtained in the epidermis of the Aloe leaf (Okamura
December 31, 2009
400
405
Q5
410
415
420
425
430
435
440
445
Q6
450
2:5
FSN
BFSN_A_354613
et al., 1996). Flavonols such as kaempeferol, quercetin, and

myricetin have recently been isolated from Aloe vera leaves
(Sultana and Anwar, 2008). It is not known whether these phenolic compounds are in the exudate, in the gel, or in both. The
antioxidant capacity and phytochemicals have recently been examined in Aloe ferox gel (Loots et al., 2007). They deduced that
polyphenols, indoles, and alkaloids were the main agent for the
antioxidant capacity.
The presence of organic acids can also be emphasized among
which malic acid has the highest content (Paez et al., 2000). This
acid is not in the exudate of the plant and it has been proposed
as one of the markers for the recognition of Aloe in commercial
products (Luta and McAnalley, 2005). Other organic acids, such
as lactic or succinic, can be present as a consequence of microbiologic or enzymatic alteration of the product (IASC, 2004).
Salicylic acid has also been detected in the Aloe gel (Atherton, 1998). The presence of certain vitamins such as the A, C,
E, B1 (thiamine), B3 (niacin), B2 (riboflavin), and folic acid,
many of them with an antioxidant capacity, have been identified
(Atherton, 1998; Lawless and Allan, 2000). Some investigators
maintain that there are also trace amounts of vitamin B12 , which
is usually only available in foods of animal origin (Atherton,
1998; Lawless and Allan, 2000; Urch, 1999). However, this
finding has not been confirmed in recent studies. Aloe gel contains fatty acids; sterols like lupeol, cholesterol, campesterol,
and -sitosterol and a large number of long-chain hydrocarbons and esters which are more typical of industrial contaminants (Reynolds and Dweck, 1999; Waller et al., 1978). Umano
et al. (1999) have isolated and identified aromatic chemical compounds in the leaves of Aloe arborescens Mill. var. natalensis
Berger using gas chromatography coupled to mass spectrometry. There were 42 alcohols, 23 terpenoids, 21 aldehydes, 9
esters, 8 ketones, 6 acids, 5 phenols, and 9 miscellaneous compounds, with a marked presence of several isomers hexenol and
hexenal.
The mineral constituents of Aloe juice have also been examined (Sahito et al., 2003; Wang, 1993). The concentrations of Cl
and K are high, whereas the Na content is smaller than the usual
content in plants. Similar to the electrolytes, the Ca and Mg were
also dominant cations. There are other minor essential minerals
such as Fe, Cu, Zn, Mg, Mn, P, Cr, Si, and Ni, and small amounts
of toxic elements such as Al, B, Ba, Sr, Cd, and Pb (Femenia
et al., 1999; Sahito et al., 2003; Yamaguchi et al., 1993; Yang
et al., 2004). The most commonly used methods for the determination of minerals include atomic absorption spectrometry
and flame emission spectrometry (Yang et al., 2004), and inductively coupled plasma (Femenia et al., 1999; Yamaguchi et
al., 1993). Several methods for the mineralization of the Aloe
samples previous analysis for atomic absorption spectromety
have been studied (Sahito et al., 2003; Yang et al., 2004). The
most effective procedure for the decomposition of the organic
matter uses concentrated nitric acid and 30% oxygenated water
(Sahito et al., 2003). A spectrophotometric method (Li et al.,
2004) based on the second derivative peak area in the chromagenic system of 1,10-phenanthroline was proposed for the
simultaneous determination of metal species, such as Fe (II),

Cu (I), and Co (II). There is no remarkable difference between
the results obtained for this method and those of inductively 455
coupled plasma.
Influential Factors in the Chemical Composition of Aloe Gel
There are many factors that can influence the chemical composition of Aloe gel which could explain the differences in the
results observed in the literature. A first factor to consider is the
different species/subspecies or varieties of A. vera used in the
investigation (Femenia et al., 1999; Saccù et al., 2001; Van Wyk
et al., 1995). Other investigators have also pointed out that other
factors decisively influence the composition of the Aloe gel,
such as the annual seasons (Grindlay and Reynolds, 1986; Leung, 1977; Meadows, 1980; Park et al., 1998; Wang and Strong,
1993; 1995), exposure to light (Paez et al., 2000), the climate
and the land (Grindlay and Reynolds, 1986; Meadows,1980),
and cultivation methods (Femenia et al., 1999; Park et al., 1998;
Saccù et al., 2001; Van Wyk et al., 1995; Wang, 2007; Wang
and Strong, 1993,1995).
The variation in the concentration of some compounds of
A. arborescens var. natalensis Berger extracts according to seasonal changes such as temperature or rainfall has been studied
(Beppu et al., 2004). Aloin A (barbaloin), aloin B (isobarbaloin),
aloenin, proteins, saccharides, polyamine concentrations, and
carboxypeptidase activity, were higher in the hotter seasons;
and that protein, saccharide, polyamine, and carboxypeptidase
activity were affected in the rainy season. Park et al. (1998) indicated that the phenolic compound contents change in function
of the climatic season. This contrasts with some results obtained
in the A. ferox exudate, in which the contents of the majority
components (Aloeresin A, aloesin, and aloin A and B) held a
relationship of 4:3:2 respectively and these three compounds
accounted for 7097% of the dry weight (Van Wyk et al., 1995).
The aloin present in the plant exudate was clearly related to its
procedence, and the minority components presented a bigger
variation (Van Wyk et al., 1995). The irrigation of the plant
affects the amount of mucopolysacharides, since the contents
were smaller in well-irrigated plants (Yaron, 1993). The Na,
K, Ca, and Mg contents, as well as the pH and fiber content,
change with the climatic season have been documented (Wang
and Strong, 1993, 1995).
There are also differences in the concentrations of different
compounds in the function of the area of the leaf being analyzed
(Beppu et al., 2004; Gutterman and Chauser-Volfson, 2000;
Wang and Strong, 1993, 1995). It has also been proven that the
phenolic compounds can vary depending on the part of the leaf
that is analyzed (Gutterman and Chauser-Volfson, 2000).
The age of the plant is an additional and decisive factor that
needs to be considered. The most significant increase in the
aloin concentration was observed in plants of 2 and 3 years
(Waller et al., 1978). The data obtained by Hu et al. (2003)
suggest that the maturity of the plant plays an important role
in the antioxidant capacity of the gel. The phenolic compound
460
465
470
475
480
485
490
495
500
505
December 31, 2009
2:5
FSN
BFSN_A_354613
510
515
520
525
530
535
contents in Aloe diminished with the age of the plant (Okamura

et al., 1996).
On the other hand, Aloe gel is very unstable as a consequence of the hydrolysis of the constituent polysaccharide observing losses of viscosity over time (Meadows, 1980). Thus,
the manipulation and preservation methods used can modify the
chemical composition and physicochemical characteristics of
the products (He et al., 2005; Kim et al., 1998; Mandal and Das,
1980). There is a decrease of the biological activity as a result of
these physicochemical modifications, therefore it is fundamental to use adequate preservation methods to maintain the therapeutic activity of the products. The addition of other natural
polysaccharides isolated from algae was beneficial to preserve
the viscosity during the preservation (Yaron et al., 1992; Yaron,
1993). The chemical composition of the derivative products of
the Aloe can also be affected during the post-harvest, especially
for the time and temperature used in the dehydration process
used in the preparation of commercial extracts (Femenia et al.,
2003; Simal et al., 2000). The variation in some of the results
described in the bibliography could be explained by the treatment and preservation of the gel after its collection (Agarwala,
1997; Briggs, 1995; Fox, 1990; Kim et al., 1998; Mandal and
Das, 1980; Marshall, 1990; Simal et al., 2000). The dehydration
temperature increases the molecular weight of the constituent
polysaccharides because of structural changes which produce
changes in the functional properties such as a decrease of the
water and fat retention capacity (Femenia et al., 2003; Simal
et al., 2000; Takeyama et al., 2002). These functional changes
could be due to the decrease of the soluble fiber content of
the Aloe gel which takes place because of the relatively high
temperature used (Takeyama et al., 2002).
MEDICAL USES AND APPLICATIONS
The use of Aloe dates from biblical times, and it has been and
is still used in traditional medicine for the treatment of numerous
540 illnesses. The beneficial effects of Aloe for health have probably
been exaggerated on many occasions. Therefore, it is necessary
to be cautious when interpreting the results, and in particular,
when applying it to the treatment of illnesses. Therefore, some
authors (Vogler and Ernst, 1999) have pointed out that although
545 there are some promising results, the effectiveness of the use of
A. vera at a topical level or previous oral consumption has not
been adequately defined as yet.
Skin and Wound Healing
The therapeutic activity of Aloe seems to work in two defined areas; on the one hand on the damaged epithelial tissue,
and on the other, on the immune system. Aloe is known well for
its topical use as an anti-inflammatory and for curing wounds
and burns, since it accelerates growth and renovation of damaged tissues, especially those affecting the epidermis. Therefore,
555 its benefit has been described in illnesses such as burns, cuts,
550
eczemas, haemorrhoids, wounds, varicose veins, cracked skin,

etc. (Reynolds and Dweck, 1999). The treatment of burns and
alterations of the skin as a result of aging or oxidative damage
by UV radiation should be given special emphasis in the topical
uses of Aloe (Capasso et al., 1998; Danof, 1993). A clinical
trial demonstrated the usefulness of A. vera for prophylaxis of
radiation-induced dermatitis (Haddad et al., 2007). When it is
compared with moisturizing creams, the topical use of A. vera
gel has positive effects on the alterations in the skin as a consequence of radiotherapy including erythema, pain, and dry and
wet desquamation (Heggie et al., 2002). There is evidence that
supports the view that the use of A. vera gel is effective for the
treatment of first to second degree burns (Maenthaisong et al.,
2007). However, well-designed trials with sufficient details of
the contents of A. vera products should be carried out to determine the effectiveness of A. vera for burn wound healing. It can
also be successfully used in treatments of skin ulcers, including
mouth ulcers, leg ulcers, and simple herpes. This is due to an
anti-viral effect of the Aloe gel in concentrations of 80% (Eshun and He, 2004). Kodym et al. (2003) have proposed the use
of eye drops containing Aloe gel and neomycin sulphate in the
treatment of inflammations and infections of the external parts of
the eye, such as conjunctivitis, eyelids, lacrimal sac, and cornea.
Aloe has a marked effect in the treatment of scars, and prevents
the formation of scars after skin lesions (Eshun and He, 2004).
The positive effect in the treatment of the wounds could also
be due to certain anti-microbial (Heggers et al., 1995) and antifungal activities (Rosca-Casian et al., 2007) usually attributed to
the Aloe gel. Thus, these authors (Heggers et al., 1995) observed
that the skin cuts in rats healed more quickly when Aloe gel was
applied. Some studies have indicated that the A. barbadensis gel
accelerates the cure of wounds in diabetic rats due to its ability
to stimulate the synthesis and maturation of collagen in fibroblasts (Chithra et al., 1998b). The hypoglycemic effect observed
could probably contribute in the acceleration of this cure.
560
565
570
575
580
585
590
Diabetes
A hypoglycemic effect in diabetic rats previous oral consumption of the Aloe gel has been indicated by some authors (Ajabnoor, 1990; Beppu et al., 1993; 2003; 2006
a,b; Bunyapraphatsara et al., 1995, 1996). Extracts of Aloe 595
gel prevented hyperglycemia in rabbits treated with alloxan
(Akinmoladun and Akinloye, 2007). These authors found that
a homemade aqueous extract had a more potent effect than a
factory-produced gel. While the investigators mentioned above
have pointed out the anti-diabetic activity of Aloe, other inves- 600
tigators (Koo, 1994; Mossa, 1985; Roman-Ramos et al., 1991;
Wagar et al., 2008) did not find these same results. In fact, Koo
(1994) found an elevation of the blood glucose levels in diabetic
mice (induced with Alloxan) with a product that contained the
Aloe gel. Okyar et al. (2001) compared the effects of the Aloe 605
gel and extract of the whole leaf on the blood glucose levels
in normoglycemic and in diabetic type I and type II rats. They
December 31, 2009
2:5
FSN
BFSN_A_354613
610
615
620
625
630
635
640
645
650
observed that the complete extract of the leaf is efficient in both

types of diabetes, which agrees with several authors (Ajabnoor,
1990; Beppu et al., 1993; Bunyapraphatsara et al., 1995; 1996).
On the other hand, the hyperglycemic effect of the Aloe gel observed in rats with diabetes type II (Koo, 1994), could explain
the negative results found when an aqueous extract of the whole
leaf, rich in gel, was used (Mossa, 1985; Roman-Ramos et al.,
1991). It is deduced therefore that the complete extract of Aloe
leaf, instead of the gel, maybe of interest in the treatment of diabetes, in particular of the noninsulin-dependent strain. The effect
of an extract from A. vera gel containing a high concentration of
polyphenols on experimentally-induced insulin resistance was
examined (Perez et al., 2007). They concluded that the A. vera
gel could be effective for the control of insulin resistance.
There are studies on the effects of A. vera in diabetic humans. Oral use of A. vera gel decreased fasting blood glucose
(by more than 100 mg/100 ml) and the hemoglobin A1c levels
in three studies of people with type II diabetes, although no control groups were considered in these studies (Ghannam et al.,
1986). In a wide study in India, A. vera gel was administered
to diabetics via bread, and the blood glucose level decreased
in 90% of the cases (Agarwal, 1985). A decrease of the blood
glucose levels was also observed in diabetic patients from New
Zealand, orally treated with A. vera gel (Yongchaiyudha et al.,
1996). Chalaprawat (1997) reported a reduction of blood glucose levels in patients administered with A. vera gel twice a day
for a nine-month period compared with placebo-receiving patients, but the differences were not stastistically significant. In a
study (Yeh et al., 2003) reviewing the use of grasses and dietary
supplements for glycemic control in diabetes concluded that A.
vera extracts show positive results according to most of the studies. It is important to clarify which compound or compounds are
the ones responsible of the hypoglycemic effect.
Besides reducing the blood glucose levels in diabetic patients, the oral administration of A. vera can be useful for reducing lipid levels in patients with hyperlipidemia (Vogler and
Ernst, 1999; Yongchaiyudha et al., 1996) and hepatic cholesterol and oxidative status in aged rats (Lim et al., 2003). The
oral consumption of A. vera gel (1020 ml/day) for 12 weeks can
reduce low density lipoprotein (LDL) cholesterol by about 18%,
total cholesterol by about 15%, and tryglycerides by 2530% in
patients with hyperlipidemia (Shapiro and Gong, 2002).
et al., 1998a,b,c; Davis et al., 1989a,c; Heggers et al., 1993) 660

and has anti-inflammatory effects (Davis et al., 1989b,c; Saito
et al., 1982), which favors the anti-ulcer effect. In a recent study
(Suvitayavat et al., 2004) on the effects of a preparation of Aloe
in models of chronic ulcers in rats, an increase of pepsin and
mucus secretion was observed and a decrease in acid secretion. 665
However, no significant differences were observed with regard
to the control group. These authors concluded that more research is needed using different doses with the aim of obtaining
more conclusive results.
Immunologic Effects
670
The action on the immunological response was postulated to some degree several years ago (Griggs, 1996; Rubel,
1983; Schechter, 1994). On the one hand the anti-tumor, antiinflammatory, and immunosuppressive activities of the gel from
certain species of Aloe has been indicated (Yagi and Takeo, 675
2003); and on the other hand, immunostimulative activities have
also been described (Im et al., 2005; Lawless and Allan, 2000;
Leung, 1977; Merriam et al., 1996; Pugh et al., 2001; Reynolds,
1985; Urch, 1999). In fact, Aloe gel has been used in nutritional
supplements in clinical trials for the treatment of the acquired 680
immune deficiency syndrome (AIDS) patients for its anti-viral
and immunological properties (McDaniel, 1987; Marshall and
Druck, 1993; Montaner et al., 1996).
Anti-Cancer Effect
Aloe extracts have been tested in the treatment of cancer and 685
positive effects have been observed in inhibiting the growth of
tumors. A wide study on lung cancer and smoking performed in
Japan suggested that the oral ingestion of Aloe juice, presumably the gel, prevented pulmonary carcinogenesis and cancer in
other tissues (Sakai, 1989). The activation of macrophages as 690
immune stimulation mechanisms was reported (Zhang and Tizard, 1996). In an in vitro study using a rat hepatocyte model,
carcinogenesis by DNA adduct formation was inhibited by an
Aloe gel fraction rich in polysaccharides (Kim and Lee, 1997).
Aloe extracts have also reported prevention or regression of 695
tumor growth (Corsi et al., 1998; Akev et al., 2007).
Gastrointestinal Effects
Antioxidant Effect
In the 1960s it was discovered that the oral intake of Aloe gel
was of interest in the treatment of peptic ulcers and other dysfunctions of the gastrointestinal tract. Thus the A. vera gel has
been satisfactorily used by patients for the treatment of inflam655 matory bowel disease (Langsmead et al., 2004). The preventive
effect against the peptic ulcers was associated with pepsin inhibition and hydrochloric acid secretion, as well as a general
detoxifying effect (Blitz et al., 1963). It has been demonstrated
that the A. vera gel is effective for healing wounds (Chithra
Long term A. vera gel intake, both the raw gel and the processed gel, in Fischer 344 rats could have beneficial effects on
pathologies related with aging, such as cardiopathies or fatal 700
chronic nephropathy, without causing deleterious effects (Ikeno
et al., 2002). These results confirm suggestions reported in previous studies (Afzal et al., 1991; McCauley et al., 1990) that
indicate that A. vera maybe of use in the prevention of thrombo
formation. The antioxidant activity of the Aloe vera gel (Aloe 705
December 31, 2009
2:5
FSN
BFSN_A_354613
barbadensis Miller) has been studied and evaluated by determining the free radical-scavenging activity of the gel by means
of the extraction with supercritical carbon dioxide (Hu et al.,
2005). Aloe vera extracts present in an equivalent amount have
710 a stronger anti-oxidant effect than butyl hydroxianisol (BHA)
and the -tocopherol, which could be of interest in the design of
functional foods, cosmetics, and medications (Hu et al., 2003).
It was deduced that some compounds located in the cortex of the
leaf were those responsible for most of the antioxidant capac715 ity of the Aloe extracts (Hu et al., 2005). Esteban et al. (2000)
have suggested that the protection of Aloe gel against aging and
damage of the skin from UV irradiation could be due to the
antioxidant efficiency of a peroxidase other than the glutathione
peroxidase. These antioxidant effects of A. vera gel, as well as
720 its antifungal and antimicrobial effects, could be involved in the
action of the gel on maintaining the quality and safety of table
grapes (Valverde et al., 2004).
Other Beneficial Effects

There are other beneficial effects that are attributed to diverse
extracts of A. vera. In a large clinical trial, an Aloe extract compared versus placebo, was used on a large number of patients
with psoriasis who were cured (Syed et al., 1996). Besides, beneficial effects at hormonal levels have been found after the use
of Aloe gel. The intake of Aloe gel decreased the calcitonin and
730 parathyroid hormone levels in a study on rats (Herlihy et al.,
1998). On the other hand, it was observed that a leaf extract
of this plant (gel of A. vera) reduces thyroid hormone levels,
although in a more moderate way than Aegle marmelos extract
(Kar et al., 2002). However, the choice of Aloe gel as a natu735 ral antithyroidal extract has advantages in mild hyperthyroidic
cases, as it does not only not exhibit hepatotoxic effects but
it is hepatoprotective in nature (Kar et al., 2002). In the field
of dentistry, it has been used to treat many dental affections.
It alleviates pain and it accelerates the healing after periodon740 tal surgery (Payne, 1970). The extract of the gel has also been
used in veterinary science for external treatments on animals,
including allergies, fungal infections, inflammations, pains, and
itching (Anderson, 1983; Northway, 1975).
725
745
BIOLOGICALLY ACTIVE COMPOUNDS

AND THERAPEUTIC ACTIVITIES
Although some physiological properties of Aloe have been

discovered and demonstrated in vitro and in vivo, nevertheless, the controversy surrounding which component or group
of Aloe components having those physiological properties is
750 not completely clarified at present. It is very probable that the
beneficial effects of Aloe are due to the sum of the effects
of each component, or that the total effect is greater than the
sum of the effects found after individual administration of each
compound (Femenia et al., 1999, 2003; Reynolds and Dweck,
Figure 2
Aloe.
Contribution of diverse components to the therapeutic action of the
1999; Talmadge et al., 2004). Consequently, the focus is moving

towards what the active principles responsible for therapeutic
effects are and these active principles could be isolated and
used in the preparation of pharmaceutical products (Reynolds,
1998).
The reasons justifying the effectiveness of the gel in the
treatment of illnesses and diverse disorders are often uncertain,
perhaps due to the fact that there are several therapeutic activities intervening together (Capasso et al., 1998). Davies et al.
(1984) used the orchestra conductor concept to explain the relationships that exist among more than 200 biologically active
compounds that Aloe contains (Fig. 2). One of these molecules,
a polysaccharide, acts like a conductor conducting a symphony
composed of all the active constituents. Therefore, this polysaccharide, like an orchestra conductor, modulates the biological
activities of the compounds that constitute the orchestra, to act
synergically. However, there are many examples in the bibliography that point out that the polysaccharides can show pharmacological and physiological activities without the help of other
components. Therefore, it is logical to think that the mucilaginous Aloe gel, which is essentially a polysaccharide, holds the
secret of the medicinal properties of the A. vera (Eshun and He,
2004).
It is practically impossible to prevent the contamination of the
A. vera gel by the chemical compounds present in the exudate
of the leaves during its commercial extraction. It is also believed
that in intact leaves, the anthraquinones and their derivates can
diffuse towards the interior of the gel from the sheath cell bundle
of the epidermis. This possibility supports the conviction of
some investigators who maintain that the healing agent passes
from the rind towards the gel where it remains. In fact, in many
cases the extract of the whole leaf is the one that possesses
therapeutic activities and not only the gel (Suvitayavat et al.,
2004).
Several mechanisms have been proposed to explain the healing properties of Aloe. However, in accordance with Spoerke
and Elkins (1980) and Meadows (1980), the action of Aloe is
simply due to its moisturizing and emollient effects. The activity of Aloe as a moisturizing agent is a popular concept which
has been known for many years (Briggs, 1995; Danof, 1987;
Fox, 1990; Marshall, 1990; McKeown, 1987; Meadows, 1980;
755
760
765
770
775
780
785
790
795
December 31, 2009
10
800
805
810
815
820
825
830
835
840
845
850
2:5
FSN
BFSN_A_354613
Natow, 1986; Watson, 1983). This moisturizing effect can explain many of its beneficial effects. In the 1960s the apparent
effectiveness of Aloe pulp was already suggested possibly because of its high water content of over 98%, which provides
water easily available for the damaged tissue without taking it
from the environment (Morton, 1961). This theory could explain
the instantaneous soothing effect that the Aloe has in burns, but
it would not justify the long-term effects on health.
Some investigators affirmed, some decades ago, that the effective compound for the cure of wounds is tannic acid (Freytag,
1954); however, this has not been confirmed to date. Other investigators (Eshun and He, 2004) have also informed about
the anti-inflammatory effects of complex polysaccharides, glycoproteins, and sulfated polysaccharides. According to some
authors (Yagi et al., 1985), the presence of lectin in the gel is
responsible for the therapeutic effect on burns. However, the
existence of diverse components in the Aloe gel might contribute to the healing of the burn (Robson et al., 1982). The
anaesthetic effect, the bactericidal action, and an antithromboxane effect could be participating in the cure of the burns. Davis
et al. (1994) demonstrated that the effectiveness of Aloe in the
treatment of wounds and the reduction of the inflammation is
due to the action of the mannose-6-phosphate, a major sugar
present in Aloe gel, which is an activator of tissue growth. It has
been postulated that the -sitosterol, present in Aloe gel, is a
potent angiogenic factor that stimulated the neovascularization
and the healing of wounds (Moon et al., 1999). A glycoprotein
fraction is involved in the wound-healing effect of Aloe via cell
proliferation and migration (Choi et al., 2001). A glycoprotein
(Pg21-2b) isolated from a preparation of A. vera gel had promoter activity of the cellular proliferation (Heggers et al., 1996;
Yagi et al., 1997), and it would therefore be involved in healing
wounds and burns. This is due to the fact that Aloe stimulates
the production of cells through the activity of amino acids which
are the basis of new cell formation. It is also due to the ability
of these amino acids to stimulate the regeneration of the deepest
layers of the skin by the synthesis of enzymes (Eshun and He,
2004).
The anti-inflammatory activity of Aloe gel is associated with
the inhibition of the cyclooxygenase activity, which prevents
the synthesis of prostaglandins that are fundamental chemical
mediators in inflammatory processes (Davis et al., 1984). Afzal
et al. (1991) indicated the possible presence of cyclooxygenase
in a homogenized A. vera leaf product. The inhibition of pain
producing substances, such as thromboxane or bradykinin is
often attributed to Aloe gel. In fact, a decrease in the thromboxane concentration has been described by topical application
of Aloe gel (Robson et al., 1982), suggesting that a substance,
not present in the gel, inhibited the arachidonic acid oxidation
(Penneys, 1982). Yagi et al. (2003) have isolated a glycoprotein,
with a 58% protein content, that inhibits cyclooxygenase and reduces thromboxane synthesis. These discoveries explain, at least
partly, the healing effects of A. vera in wounds. Bradykinin is
a chemical mediator in a variety of inflammatory disorders that
produces pain through the stimulation of sensorial primary neu-
rons, and it causes the secretion of diverse neuropeptides (Averbeck and Reeh, 2001). The anti-bradykinase activity observed
in fractions of A. barbadensis is caused by a termosensible protein. Therefore, this sustains the hypothesis of the use of Aloe
extracts in inflammatory states (Bautista-Perez et al., 2004).
The presence of salicylates is more speculative because of
their involvement in aspirin type effects (Canigueral and Vila,
1993; Klein and Penneys, 1988; Marshall, 1990; Robson et al.,
1982; Shelton, 1991), although differences have been observed
between natural salicylates and synthetic aspirin (Frumkin,
1989). Lactate of magnesium, another simple substance constituent of the gel, inhibits histamine production by the inhibition of histidin decarboxylase (Briggs, 1995; Danof, 1987; Fox,
1990; Marshall, 1990; McKeown, 1987; Natow, 1986; Rubel,
1983). Robson et al. (1982) found salicylate, lactate, and magnesium in Aloe extracts, and suggested that, the anaesthetic activity
could be due to an aspirin type effect, the high content of the
ion magnesium, or possibly, to both components that act synergically. These authors also postulated that anthraquinone compounds, such as emodin and aloin could be hydrolyzed to salicylates by Kolbes reaction. Other authors (Hutter et al., 1996)
found anti-inflammatory effects in the C-glucosyl chromone
from Aloe barbadensis.
The elevation of blood glucose in diabetic mice intraperitoneally given the aloe carboxypeptidase was restrained when
compared to the control group (Beppu et al., 2006a). Therefore,
the inhibitory effect on the enhancement of vascular permeability related to the vascular acute inflammatory response at
streptomycin-induced lesions of pancreatic islets was involved
in the action mechanism of the aloe carboxypeptidase enzyme
(Beppu et al., 2006a). These authors (Beppu et al., 2006b) suggest that a fraction powder, derived from the leaf skin juice of A.
arborescens Miller var. natalensis Berger, alleviates the burden
of insulin secretion as it has an inhibitory action on the glucose
absorption in the jejunum of rats.
Although some anti-cancer activity has been demonstrated,
it is not clear as to which compounds are responsible for them.
The anti-cancer activity has been attributed to two Aloe fractions, glycoprotein (lectins) and polysaccharides. Besides, the
hemoaglutination activity of the lectin type substances promote
the growth of the normal cells and inhibit the growth of the
tumor cells (Winters, 1991, 1993). The Aloctin A, isolated from
A. arborescens, inhibited the growth of induced fibrosarcoma
in rats by an immunological mechanism (Imanishi et al., 1981).
The crude A. vera extract showed greater antitumor activity
than the Aloctin I (Akev et al., 2007). Therefore, the synergistic effect of the phytochemicals present in A. vera may be
responsible for this cancer preventive activity. The Aloemannan
isolated from A. arborescens, inhibited the growth of a sarcoma
implanted in mice (Yagi et al., 1977), and another polysaccharide fraction obtained from A. vahombe, reduced the growth of
a fibrosarcoma in mice, perhaps by the stimulation of phagocyte activity (Ralamboranto et al., 1982). Polysaccharides of A.
barbadensis Miller also have antigenotoxic properties and are
inhibitors of the promotion of tumors, and therefore, they have
855
860
865
870
875
880
885
890
895
900
905
December 31, 2009
2:5
FSN
BFSN_A_354613
910
915
920
925
930
935
940
945
950
955
960
been proposed as chemopreventive agents (Kim and Lee, 1997;

Kim et al., 1999). The injection of Acemannan in mice inhibited the growth of implanted murine sarcoma and decreased the
mortality by around 40% (Merriam et al., 1996). Some fractions
of polysaccharides involved with cell proliferation and cancer
have recently been isolated. So, Veracylglucans A, B, and C
have anti-inflammatory effects, whereas Veracylglucans A and
B possess anti-proliferative effects, Veracylglucan C enhances
cell proliferation (Esua and Rauwald, 2006).
Anthraquinones, present in the leaves of Aloe and other vegetable products, are perhaps involved in carcinogenesis; however, the scientific information is still not conclusive (Lee and
Park, 2003). While there are investigators (Kim and Lee, 1997;
Pecere et al., 2000; Sakai, 1989; Tsuda et al., 1993) that indicate
antigenotoxic effects and apoptosis on diverse knitted organs or
tissues such as the stomach, colon, or liver, other authors (Lee
et al., 1998; Mueller and Stopper, 1999; Schorkhuber et al.,
1998; Strickland et al., 2000; Wolfle et al., 1990) pointed out
the promoter effects of tumors and the genotoxicity and angiogenic activity on the skin, colon, and liver. The application of
aloe-emodin, vehiculized in ethanol, on the skin of mice in combination with exposure to UV B (280320 nm) radiation produced a skin tumor containing melanin (Strickland et al., 2000).
However, the aloe-emodin showed antileucemic activity in mice
(Kupchan and Karim, 1976), and it had a selective anti-cancer
activity against neuroectodermal tumors (Pecere et al., 2000).
Moreover, in agreement with some preclinical studies (Chen
et al., 2007), the aloe-emodin is a suitable and novel chemotherapeutic drug candidate for the treatment of human gastric carcinoma. Besides, Aloin, due to its less undesirable side effects and
antimetastatic potential compared to other currently used therapeutic treatments, has been proposed as the agent of choice
for the treatment of human cervical carcinoma (Niciforovic
et al., 2007). In contrast, the hydroxyanthraquinones with hydroxyl groups in positions 1 and 8 may present tumor promoter
activities (Wolfle et al., 1990). The emodin acts by blocking
and reducing the mutagenicity and DNA adducts induced by
1-nitropyrene (Su et al., 1995). In mutagenecity assays with
Salmonella typhimurium, a variety of compounds structurally
related with hydroxyanthraquinones presented mutagenic effects (Westendorf et al., 1990). It has been suggested that the
inhibition of the enzymatic activity of an enzyme, denominated topopisomerase II, contributes to the genotoxicity and
mutagenecity induced by anthraquinones (Mueller and Stopper, 1999). The cytochrome P450 responsible for the biotransformation of anthraquinones, like the aloe-emodin, could be
involved in the activation of these compounds (Mueller et al.,
1998).
With respect to the action on the immune system, it appears that the constituent polysaccharides have immunomodulator properties, with an emphasis on the Acemannan in them
(Agarwala, 1997; McAnalley, 1988; Schechter, 1994). On the
one hand, the neutral polysaccharides, Aloemannan and Acemannan, have anti-tumor, anti-inflammatory, and inmunosupressive properties, while glycoprotein fractions with bradyki-
11
nase activity and stimulants of the cellular proliferation, were

identified in the nondialyzed fraction of the Aloe gel from several species (Yagi and Takeo, 2003). A wide variety of pharmacological properties are attributed to the Acemannan such as
its antiviral effects (Leung, 1977), activation of macrophages, 965
monocytes and antibodies (Marshall et al., 1993; Reynolds,
1985; Zhang and Tizard, 1996), stimulation of the cells T
(Urch, 1999) and tumor necrosis factor (Marshall et al., 1993),
and induction in the production of nitric oxide (Lawless and
Allan, 2000). The Acemannan acts as an external bridge be- 970
tween unknown proteins, such as viruses or microorganisms,
and macrophage particles, facilitating phagocytosis (Marshall
and Druck, 1993). However, high concentrations of Acemannan are needed to get modest effects in the macrophage activation. This suggests that Acemannan is not very potent or that 975
there are other more potent components, in trace amounts as
contaminants, whose presence is high enough to produce the
observed effects. Aloeride, a high molecular weight polysaccharide, has shown a very potent immunostimulatory activity
and it is present in trace amounts as a contaminant. Although 980
Aloeride is comprised of only 0.015% of dry weight Aloe juice,
its potency for macrophage activation fully explains the activity
of the raw juice (Pugh et al., 2001). Im et al. (2005) have reported the immunomodulatory activity and the molecular size of
polysaccharides isolated from Aloe. They deduced that the frac- 985
tion of polysaccharides with molecular weights of between 400
and 5 KDa, exhibited the most potent macrophage-activating
activity as determined by the increase in cytokine production
release, nitric oxide production expression of surface molecules
and phagocytic activity. Besides, in agreement with in vivo 990
and in vitro studies, these polysaccharides showed the highest
anti-tumor activity.
Some chemical compounds have also been isolated from
the extract of A. barbadensis with a similar immunomodulatory activity to that of lectin (Qiu et al., 2000). The presence 995
of two dihydrocoumarins with immunomodulatory and antioxidant properties has also been reported (Zhang et al., 2006).
Acemannan is a key compound that stimulates the immunity
mediated by the cells, which is deficient in HIV infection (Marshall and Druck, 1993). A similar effect was observed with the 1000
lectin (Imanishi and Suzuki, 1984). In a trial with advanced HIV
patients treated with Acemannan, no increase of the CD4 cells
or viral burden was found (Montaner et al., 1996).
Recently there has been a lot of interest in the biological effects of polysaccharides, which are bigger and more di- 1005
verse than was originally thought. Some of these substances
present in plants with variable chemical composition are well
known entities, and on occasion the chemical structures are not
well-established (Franz, 1989; McAuliffe and Hindsgaul, 1997;
Tizard et al., 1989). Antibacterial, antifungal, and antiviral activ- 1010
ities of the gel have often been mentioned (Klein and Penneys,
1988; Marshall, 1990; Shahnaz et al., 1993), while their antioxidant effects are of increasing interest (Ikeno et al., 1998,
2002; Lee et al., 2000). Lee et al. (2000) have isolated and
identified a derivative chromone compound from methanolic 1015
December 31, 2009
2:5
FSN
BFSN_A_354613
12
1020
1025
1030
1035
1040
1045
1050
1055
1060
1065
extract of A. barbadensis Miller gel with a potent antioxidant

activity similar to the -tocopherol. This compound was found
to be a chromone. Aloe vera antioxidant compounds have been
examined against lipid peroxidation using mitochondrial and
microsomal enzymes of rat livers. The relationship between
the anti-inflammatory and antioxidant activities and the chemical structures of derivative compounds of the aloesin isolated
from Aloe species, such as the cinamil, p-coumaroyl, feruloyl,
and caffeoyl aloesin has been studied. The isorabaichromone
showed a potent antioxidant efficiency among the derivates of
studied Aloesin (Yagi et al., 2002). These authors deduced that
these activities could be associated with acyl groups. A glycoprotein fraction with 14 KDa of molecular weight from A.
vera gel was shown to have radical scavenger activity and inhibited cyclooxygenase 2 and thromboxane A2 synthase (Yagi
et al., 2003). Both glycoprotein fractions and aloesin-related
compounds play an important role in the anti-inflammatory activity of A. vera leaf gel (Yagi et al., 2002; Yagi and Takeo,
2003).
It is a well-known fact that the consumption of constituent
polysaccharides of the fraction of soluble fiber modulates the intestinal absorption of glucose, besides reducing cholesterolemia.
Therefore, the indicated antidiabetic effects of Aloe maybe due
to the components of soluble polysaccharides present in the
gel. The role of certain minerals present in the A. vera gel has
also been studied in biochemical alterations related to diabetes
in rats. The results clearly indicate that the presence of several trace elements in the gel contribute to their hypoglycemic
activity (Rajasekaran et al., 2005).
TOXICOLOGICAL ACTIVITIES
The wide and extensive use of the plants as medicines has
been growing, mainly due to a certain dissatisfaction of the general population with the results of traditional medicine. However, on many occasions this use of medicinal plants is not as safe
as commonly thought (Rodrguez-Fragoso et al., 2008). Most
Aloes are not toxic but a few are extremely poisonous (Atherton,
1998). Therefore, it can be dangerous to use medicinal plants
without evaluating their possible adverse effects (Capasso et al.,
2000).
A controlled toxicological evaluation of the administration
of Acemannan administered by injection to mice, rats, and dogs
was carried out without finding adverse effects. Hematology
and serum chemistry determinations and urinalyses conducted
at 1, 3, and 6 months all showed values within the normal
range. After necropsy examinations, organ weights and gross
and microscopic pathology from the treated rats were similar to
corresponding controls. However, an increase in the number of
leukocytes in the circulation was found which is probably due to
the stimulation of the immune system. There was also infiltration of macrophages in the liver, lungs, and spleen (Fogleman et
al., 1992), which is in agreement with that indicated by Zhang
and Tizard (1996), who reported that Acemannan stimulates
the production of macrophages. A study of the ingestion of a

diet containing 1% Aloe gel in rats did not adversely affect
growth or have any pathological effects (Herlihy et al., 1998). 1070
It was also observed that the Aloe gel did not have hepatotoxic
effects, but rather it was hepatoprotective (Kar et al., 2002).
Other authors (Yeh et al., 2003) have pointed out that the products prepared from Aloe gel seem quite safe. Life-long A. vera
ingestion did not cause any obvious harmful and deleterious 1075
side effects in male Fisher 344 rats (Ikeno et al., 2002). Several
polysaccharides isolated from A. vera gel were nontoxic and exhibited an anti-tumor activity in a murine model (Leung et al.,
2004).
Some authors (Briggs, 1995; Ernst, 2000; Klein and Penneys, 1080
1988) have warned about possible allergic side effects. Some
isolated cases have been observed. A single case of the appearance of an eczema after topical and internal application
of A. vera gel was followed by another in a hypertensive patient treated with A. arborescens gel (Shoji, 1982). On the other 1085
hand, a study on 20 human subjects treated with Aloe gel and
exposed to UV radiation showed a persistent pigmentation of
the skin (Dominguez-Soto, 1992). The effect of allergic dermatitis was described again in patients that used Aloe gel for
the treatment of chronic leg ulcers (Hogan, 1988). Other au- 1090
thors (Zawahry et al., 1973) confirmed that Aloe gel was of
interest for the treatment of this chronic lesion, although local
pain was observed in the beginning, which was attributed to
the improvement in circulation. In a study on burns, Aloe gel
could also worsen to some extent the cure of the wound by not 1095
fulfilling all the healing requirements (Kaufman et al., 1988).
In clinical studies (Fulton, 1990), the multiple factors involved
in the healing of wounds were studied. The zones tried with
Aloe healed more rapidly and completely than the untreated
zones, although burning sensations were perceived at times. A 1100
severe burning sensation was also observed followed by longterm erythema in a case of local application of Aloe (Hunter and
Frumkin, 1991).
The Food and Drug Administration (FDA) Special Nutritional Adverse Event Monitoring System listed 30 matches for 1105
Aloe in 27 adverse event reports. In 7 matches of 30 events,
the only ingredient listed was A. vera. Adverse events reported
included stomach problemsnausea, dizziness, and tiredness;
buzzing and tingling in ears, pressure in head, dizziness, increased blood pressure, panic attacks, teeth chattering, insom- 1110
nia, inability to concentrate, and memory problems; paroxysmal atrial fibrillation with rapid ventricular response with
symptomatic light-headedness and palpitations; red, itchy rash;
shakiness, no strength, dizzy spells, aseptic meningitis, and
1115
stroke.
There are several single-case reports on toxicity in humans, but there are no published controlled toxicology studies
(Steemkamp and Stewart, 2007). Two cases of possible oral
A. vera induced hepatitis have recently been reported (Rabe et
al., 2005; Bottenberg et al., 2007). One patient experienced mas- 1120
sive intraoperative bleeding after consumption of A. vera tablets,
which could have been due to a herb-drug interaction between
December 31, 2009
2:5
FSN
BFSN_A_354613
1125
1130
1135
1140
1145
1150
1155
1160
1165
1170
1175
Aloe and sevoflurane (Lee et al., 2004). Luyckx (2002) reported

a patient with acute renal failure following Aloe ingestion where
no other cause was found. A case of severe vomiting after Aloe
ingestion was reported by Wang et al. (2003). On the other hand
the additional decrease of the blood glucose levels caused by the
A. vera gel apart from that due to the antidiabetic drugs (Bush
et al., 2007), could increase the risk of hypoglycemia. Overuse
of Aloe, along with cardiac glycoside drugs, can increase the
risk of toxicity and might potentiate diuretic-induced potassium
depletion, increasing the risk of hypokalemia (De Smet, 2002;
Shaw et al., 1997). Besides, there is some concern based on
anecdotal reports that Aloe exudates might induce abortion and
stimulate menstruation (Federici et al., 2005; Bush et al., 2007).
A factor that could be decisive regarding the toxicity of these
products is the presence of phenolic substances of the exudate,
particularly the anthrone C-glycosides, in the gel-like contaminants. This contamination by anthraquinone derivatives may
have played a role in the adverse events such as laxative effects
reported in A.vera gel (Ishii et al., 1990; De Smet, 2004). Aloeemodin has been extensively studied for apoptosis-inducing effects. Treatment with aloin induces apoptosis in Jurkat cells,
which are an established model for apoptosis inducing effects
(Buenz, 2008). It has been demonstrated that aloin, besides its
purgative effects, can have carcinogenic properties due to its
deleterious action on the cellular DNA when certain intake levels are reached (Lee et al., 1998; Mueller and Stopper, 1999;
Schorkhuber et al., 1998; Strickland et al., 2000; Wolfle et al.,
1990). Aloe supplements not containing aloin may be safer than
Aloe supplements containing aloin, and the aloin should be considered in addition to concentrations of Aloe-emodin (Buenz,
2008). It has been demonstrated that the yellow leaf exudates
killed fibroblasts in cell cultures, while the clear gel stimulated
cell growth (Danof, 1987). Again the duality arises between
the colorized and decolorized gels (Davis et al., 1986), the former having a much lower healing capacity. The decolorized gel
reduced the wound swelling caused by infiltration of polymorphonuclear leukocytes to a greater extent than the colorized gel
(Davis et al., 1986). This colorized gel also reduced the diameter
of the wound more quickly (Davis et al., 1987).
Studies comparing a commercial stabilized gel with fresh
gel of the plant previously dialysed to separate the components
of low molecular weight were carried out. Cytotoxic effects
were observed in the sample of commercial gel, which is associated with substances introduced during processing (Winters
et al., 1981). Some commercial samples that contained yellow
saponins had cytotoxic effects in fibroblast cell cultures (Danof
and McAnalley, 1983). Later studies carried out on fractions of
low molecular weight (<10 KDa) of whole leaves of A. vera,
have shown that these have a disruptive effect on monolayer
cell cultures and they inhibit neutrophils from the liberation of
reactive species of oxygen (Avila et al., 1997). Aloe-emodin
and aloin had similar effects. For these reasons aloin has been
included in a list of twelve compounds that, due to its pharmacological activity, the European Union has set a maximum allowed
concentration in alimentary products (European Council, 1988).
13
QUALITY CONTROL AND LEGAL ASPECTS

The legal status and the practical use of traditional herbal
medicines vary significantly from one country to another, 1180
thereby complicating the free circulation of such products within
the European Union. Adequate information is needed by the
consumers, including a clear distinction between the medicinal and the non-medicinal use of some herbal products and
preparations (Silano et al., 2004). By July 2007, the European 1185
Commission presented a report on the advisability of incorporating additional categories of substances into the existing legal
provisions allowing the use of herbal substances and preparations in medicines as well as in food supplements (Committee
of Herbal Medicinal Products, 2007). In this report the concen- 1190
trated and dried juice of the leaves were evaluated. It was concluded that in view of existing possible risks, such traditional
use cannot be recommended and referred to in the Community list of herbal substances, preparations, and combinations
thereof for use of traditional herbal medicinal products. This is 1195
in accordance with the German pharmacovigilance actions for
anthranoid-containing laxatives (Committee of Herbal Medicinal Products, 2007). Aloe vera is one of the natural commercial
product derivates of plants that has grown most in popularity
and interest in the last few years. In 2003 alone, it was one of 1200
the ingredients most frequently used (1557 new products) in
the preparation of new foods, cosmetics, and pharmacological
products (Hale, 2003).
The Aloe gel is expensive, therefore it is not surprising that
some producers try to increase their business profits by adding 1205
water to the Aloe components (Cordella et al., 2002; Diehl and
Teichmuller, 1998). A lot of confusion exists about the effectiveness of the large variety of Aloe products on the market.
Consumers often wonder what is the best Aloe vera? Unfortunately, there is no easy way to distinguish an adulterated 1210
product from an unadulterated one. Although price can be a
guide, the most expensive Aloe is not always the best. In conclusion, the way the consumer judges the Aloe is usually based
on its empirical results. If there is no improvement in the pathology for which it is used, the consumer changes brand and tries 1215
again.
Several factors including the harvest of the leaves, their
preservation and distribution, can cause Aloe to be of a lower
quality thereby reducing its beneficial effects. Many of the inconsistencies of the clinical results in the evaluation of its ther- 1220
apeutic effectiveness are because of how the gel was treated
from when the leaf was cut to the final product, or even the conditions of growth of the plant (Yaron, 1993). After collecting
the fresh leaves which must then be used immediately in the
production process, or they should be appropriately frozen to 1225
prevent the loss of their biological properties which can occur
as a result of the oxidation and hydrolysis of the gel (Coats,
1979). It is important to separate the gel from the outer cortex
perfectly. The addition of celullase can facilitate the mechanical
separation. After the aloe liquid obtained is treated with acti- 1230
vated carbon to remove aloin and anthraquinones, which have
December 31, 2009
2:5
FSN
BFSN_A_354613
14
Q7
1235
1240
1245
1250
1255
1260
1265
1270
laxative effects (Cobble, 1975). The therapeutic value of Aloe

diminishes a lot if the sterilization procedure is based on the
application of a high temperature for long periods of time. If the
heating of the product is increased, the elimination of bacteria
is favored, but the mucopolysaccharides and other active compounds of the Aloe are partially destroyed, and consequently,
decreases its effectiveness (Lawless and Allan, 2000). In the
cold-processing technique, the use of enzymes such as glucose
oxidase or catalase has been proposed to inhibit the growth of
aerobic microorganisms (Coats, 1994). Besides, exposing gel
to UV irradiation followed by ultra-filtration was reported as a
way of sterilizing Aloe gel (Coats, 1994). The stabilization of
the gel can be achieved using preservatives and other additives
like sodium benzoate, potassium sorbate, citric acid, vitamins C
or E (Cerqueira et al., 1999).
Management quality (ISO9000:2000) and safety (systems
HACCP; hazardous analysis and critic control points) systems
have been developed by the food industry to ensure biological
integrity, sensorial stability, and the quality of the final product
prepared from the Aloe gel (He et al., 2005). It was revealed
that the safety control points were the addition of vitamin C and
citric acid, and pasteurization; while the quality control points
were the reception of raw materials, filleting operation, grinding or homogenization, pectolytic enzymes addition, filtration,
addition of vitamin C and citric acid, deaeration, pasteurization,
flash cooling, and storage (He et al., 2005).
Therefore, with a market of dietary supplements saturated by
a large variety of Aloe products, methods to distinguish quality
products from altered or fraudulent products are needed as much
by consumers as by industry. However, it is difficult to establish
reference methods to determine the different compounds due
to the complexity and variability of the derivative components
of the plants (Blumenthal and Milot, 2004; Reif et al., 2004).
At present, simple, reproducible, and economic techniques to
determine the content of A. vera in commercial products are not
suitable (Eberendu, 2004). To carry out an exhaustive quality
control of commercial food products containing A. vera, the
following analyses should be carried out (Lachenmeier et al.,
2005):1) Investigation of the authenticity; 2) Test for identification of inadmissible preservatives; and 3) Determination of the
aloin content.
Investigation of the Authenticity

According to some investigations, there is a high number of
commercial products stating a certain quantity of A. vera gel
on the label that was found to be lower in the actual product
(De Smet, 2004; Diehl and Teichmuller, 1998; Pelley et al.,
1998). Of the many Aloe-based products on the market, few
contain more Aloe than is claimed on the labels; others have
1280 lesser amounts of Aloe than claimed on the labels; and some
contain no Aloe at all. To make sure that one is buying a product
containing Aloe and paying a reasonable price, it is important
to identify and quantify the Aloe gel used in the preparation
1275
of the commercial product, as well as to recognize possible

adulterations or dilutions. Therefore, on the label it is advisable 1285
to see the logotype of the International Aloe Science Council
(IASC), a nonprofit making international organization, whose
aim is to improve and to standardize the Aloe industry.
Adulteration is a major concern for the A. vera market, mainly
because of the high cost of the raw materials. Aloe can also be 1290
found in some of the most adulterated new products. Its dilution
with cheaper substitutes is the most common form of adulteration (Cordella et al., 2002). Historically, the most common
substance used to adulterate Aloe gel powder is maltodextrin
(Kim et al., 1998). Glucose, glycerine, and malic acid have 1295
also been reported (Pelley, 1992; Pelley et al., 1993). There
have been several attempts at establishing methods to determine
adulteration in A. vera commercial products. Many methods
have been developed to detect adulteration and establish the authenticity of Aloe gel powders. L-malic acid and some phenolic 1300
compounds (aloesin, aloin A, and aloe-emodin) have been proposed as markers (Kim et al., 1998; Pelley, 1992; and Pelley
et al., 1993), although their concentrations in Aloe gel powders
can vary significantly (due to normal biological variability) and
depend on the manufacturing process. Carbohydrate analysis 1305
has also been considered. However, in this case only adulteration with sugars (i.e. glucose, sucrose) or polysaccharides (i.e.
maltodextrin) could be revealed (Kim et al., 1998).
The identity, purity, and the quality of Aloe vera can be
determined using a proton nuclear magnetic resonance spec- 1310
troscopy method, HPLC or other traditional wet chemistry methods (IASC, 2004). Identification is based upon polysaccharides
which possess the 2,3,6 acetylation pattern that is unique to
Aloe. Quality is measured by the profile of organic acids some
of which are native (malic acid) to Aloe, while others (lac- 1315
tate, succinate, fumarate, formate, and acetate acids) indicate
possible microbial contamination. Purity is determined by the
absence of foreign materials.
Marker compounds, biologically active or not, must definitively be proposed for establishing the amount of Aloe gel that 1320
a determined product contains (Blumenthal and Milot, 2004).
Diverse markers have also been proposed for the quality recognition of different botanical materials or for the recognition of
possible adulterants. One of the main problems in the development of valid methods for Aloe products is the absence of 1325
standardized and safe reference material, as well as methods for
evaluating bioactivity to perform a quality analysis (Luta and
McAnalley, 2005; Reif et al., 2004). The IASC is in the process
of formulating a reference standard for Aloe gel to be used for
the emission of certifications concerning whether certain prod- 1330
uct contains Aloe in the quantities stated on the label, and also
whether this product is well preserved. These standards must
have contents of parameters such as total solids, Ca, Mg, malic
acid, and polysaccharides to be able to evaluate the presence of
Aloe gel (IASC, 2004; Luta and McAnalley, 2005). The produc- 1335
tion, validation, preservation, and distribution of these chemical
compounds of reference or botanical reference standards for
quality control in herbal preparations is, on many occasions,
December 31, 2009
2:5
FSN
BFSN_A_354613
1340
1345
1350
1355
1360
1365
1370
1375
1380
very laborious and expensive (Flaster and Lassiter, 2004; Reif

et al., 2004).
Ross et al. (1997) determined the mucilage content of A.
vera in commercial products by means of exclusion chromatography. These authors applied it to 18 commercial samples of
Aloe, observing very variable contents. In half of the samples, the contents ranged between 0.22 and 1.30 mg/ml, and
the mucilage was not detected in two of them. Another method
of discovering whether an Aloe commercial product is of appropriate Aloe quality and quantity, is to know the number of
mucopolysacharides. This is sometimes included on the label.
The highest therapeutic value is in the products containing between 10,000 and 20,000 mucopolysacharides per litre (Lawless
and Allan, 2000). Nine powdered concentrates of A. vera gel,
obtained from leading international suppliers, were examined
and compared with fresh A. vera gel (Bozzi et al., 2007). The
quality of commercial A. vera gel powder samples analyzed by
NMR was found to be very inconsistent, and in some cases very
poor. Only three products out of the nine analyzed contained
satisfactory amounts of Acemannan.
Several methods have been developed and they could be considered as a part of a certification process. A quick and simple
colorimetric method based on proving the absence of Acemannan (Garifallidi et al., 2004) was proposed. Acemannan is the
only polysaccharide in A. vera gel that causes a displacement
of the absorbance of the Congo red due to the formation of a
complex. Kim et al. (1998) also developed a simple and accurate method to detect the adulteration of commercial Aloe gel
powder. This method is based on the determination of ash contents and constituent sugars of polysaccharide fractions using
gas chromatography. The maltodextrin content in adulterated
products was determined by HPLC and thin layer chromatography (Kim et al., 1998). The determination of the total ion
contents in a commercial Aloe product could be an indicator of
the purity (Pelley et al., 1998). However, these authors emphasized that the most practical form of differentiating authentic
Aloe from the adulterated or the fraudulent ones is based on the
use of many more parameters than in the determination of only
one marker substance. Therefore, Saccù et al. (2001) have proposed the determination of volatile compounds for GC-MS and
phenolic compounds for HPLC as a useful analytical tool for
identifying the origin and type of Aloe used in the elaboration
of the commercial product.
Test for Identification of Inadmissible Preservatives
Commercial products available worldwide often contain stabilizers and preservatives since some components are subject to
1385 oxidation. It is important to demonstrate the presence of inadmissible preservatives in commercial products containing Aloe.
Many Aloe products are preserved by sorbic acid addition or
benzoic acid over 1000 mg/l. As the preservation of Aloe juice
is prohibited in the European Union (European Parliament and
1390 European Council Directive, 1995), some producers add ascorbic acid to their products and they describe their juices of Aloe
15
as dietary supplements. This is done to avoid the application

of the previous European directives, since dietary supplements
can contain preservatives. It is necessary to point out that Aloe
juices do not contain concentrated nutrients or other ingredi- 1395
ents of dietary value and with the addition of ascorbic acid the
juices of Aloe do not qualify as dietary supplements. In this
way, all the vegetable juices could have added vitamins, and
then be described as dietary liquid supplements. Therefore the
addition of preservatives above 2000 mg/l to vegetable juices 1400
would evade the current law on preservatives. The qualification
of A. vera juices or gels enriched with vitamin C as dietary
supplements is therefore inadmissible. In a study performed on
commercial drinks containing A. vera, it was proven that there
was a considerable number of samples containing inadmissible 1405
preservatives, which suggests that the controls in relation to the
preservatives used should be intensified to assure the quality of
the products (Lachenmeier et al., 2005).
Determination of the Aloin Content
Aloe vera gel should not contain aloin or other hydroxyan- 1410
thracene derivatives, as they are exclusively concentrated in the
leaf skin. However, the mechanical separation process is not
always complete, so some Aloe exudate can be found in the gel.
The LOAEL (lower observed adverse effect level) for aloin is
estimated at 11.8 g/Kg body weight (Zhou et al., 2003). Aloe 1415
supplements not containing aloin may be safer than Aloe supplements containing aloin, and the aloin should be considered in
addition to concentrations of aloe-emodin (Buenz, 2008). Therefore, A. vera food products for human consumption must be free
of aloin, with an existing maximum threshold of 0.1 mg/l (Euro- 1420
pean Council, 1988). There are standardized methods available
for the detection and determination of aloin in samples containing Aloe (Lachenmeier et al., 2005; Yamamoto et al., 1985;
Zonta et al., 1995). A capillary zone electrophoresis method for
the determination of the active Aloin and Aloe-emodin compo- 1425
nents in A. vera has been developed to find a simple and low-cost
method to control the quality of the herb (Wang et al., 2000).
Lachenmeier et al. (2005) concluded that only one of the 24 analyzed samples contained aloin in an amount above the admitted
maximum value, concluding that the producers have improved 1430
not only their production methods, but also their quality and
safety. In another paper (Bozzi et al., 2007), the Aloin A and
B was determined in commercial A. vera powders and variable
concentrations were found from trace levels to 16 mg/Kg. However, these concentrates are generally added to food products or 1435
beverages at the maximum level of 0.1%. Therefore, the aloin
concentration is far below the regulatory limit for all the samples
analysed.
CONCLUDING REMARKS
Only four species of the over 360 known species have been 1440
studied in relation to their therapeutic properties. There are two
December 31, 2009
2:5
FSN
BFSN_A_354613
16
1445
1450
1455
1460
1465
1470
1475
1480
1485
1490
products extracted from the Aloe leafyellow exudate, rich

in anthraquinoneswhich is used as a laxative, and gel that
has traditionally been used as a remedy for a great number of
disorders and ailments. The heterogeneous nature of the Aloe
products as well as their variable chemical composition, often
cause confusion on their therapeutic and toxicologic activities.
Most of the Aloe vera gel is water, representing 99%, so the
contribution to the macronutrient intake is low. The dry extract
of the gel is mainly composed of carbohydrates, emphasizing
the lineal polymers of mannose with random substitutions of
glucose, other monosaccharides, and uronic acids. These soluble polysaccharides have -1,4 linkages and a variable degree
acylation. Although, the content of nitrogen is low, the presence
of glycoproteins, enzymes, free aminoacids, and peptides can
contribute to the functional properties. There is a wide variety
of nutrient and no nutrient compounds in low concentrations
such as vitamins, minerals, phenolics, and orgacic acids. Many
factors influence the chemical composition, and therefore the
efficacy of Aloe gel, such as species/subspecies or varieties,
climate and exposure to light, land, irrigation, and cultivation
methods.
Current scientific investigation is producing evidence about
its multiple beneficial effects at a topical level, but apart from
this, in vitro and in vivo tests have demonstrated diverse therapeutic effects after oral consumption. Hypoglycemic effect,
treatment of peptic ulcers, and gastrointestinal dysfunctions,
immunologic, antioxidant, and anti-cancer effects have been attributed to the oral use of Aloe vera gel repeatedly. There are
a number of discrepancies about its therapeutic properties, and
clinical studies have not always found it to be effective. Thus,
it is important to conduct wider, more rigorous, and conclusive
clinical studies to confirm or discover some of its biological
and therapeutic properties; and to clarify which component or
components, acting alone or together, are responsible for the
different therapeutic effects. Although, some single-case studies have warned about some possible toxicologic and allergic
side effects, in agreement with existing data, Aloe gel is reasonably safe, without serious toxicological risks. However, it is
necessary to control the content of phenolic compounds.
The control of the biologically active principles of Aloe gel
and their preservation is complex and is still not resolved. Many
commercial products may have partially lost these active principles, and as a consequence, their biological effects. Thus, it
is essential to have suitable, simple, and sufficiently contrasted
methods as well as adequate reference material, to issue the
corresponding quality certificates. The quality control should
be guided towards three fundamental objectivesthe establishment of the authenticity, recognition of fraudulent management,
and aloin content control.
ACKNOWLEDGEMENTS
This work was carried out within the programs research
developed by the Food Quality Canary Institute. The authors
gratefully acknowledge the help of Dr. Rodolfo Rios Rull for

the assistance in the preparation of the manuscript. Besides, the 1495
authors acknowledge the help of Patrick Dennis for improving
the English in this paper.
REFERENCES
Afzal, M., Ali, M., Hassan, R. A. H., Sweedam, N., and Dhami, M. S. I.
(1991). Identification of some prostanoids in Aloe vera extracts. Planta Med. 1500
57(1):3840.
Agarwal, O. P. (1985). Prevention of atheromatous heart disease. Angiology
36(8):485492.
Agarwala, O. P. (1997). Whole leaf aloe gel vs. Standard aloe gel. Drug Cosmet.
Ind. 160(2):2228.
1505
Ajabnoor, M. A. (1990). Effect of aloes of blood glucose levels in normal and
alloxan diabetic mice. J. Ethnopharmacol., 28(2):215220.
Akev, N., and Can, A. (1999). Separation and some properties of Aloe vera L.
leaf pulp lectins. Phytother. Res. 13(6):489493.
Akev, N., Turkay, G., Can, A., Gurel, A., Yildiz, F., Yardibi, H., Ekiz, E. E., 1510
and Uzun, H. (2007). Tumor preventive effect of Aloe vera leaf pulp Lectin
(Aloctin I) on Ehrlich ascites tumors in mice. Phytother. Res. 21:1070
1075.
Akinmoladun, A.C. and Akinloye, O. (2007). Prevention of the onset of hyperglycaemia by extracts of Aloe barbadensis in rabbits treated with alloxan. 1515
African J. Biotechnol. 6(8):10281030.
Anderson, B. C. (1983). Aloe vera juice: A veterinary medicament? Comp.
Cont. Educ. Pract. 5:S364S368.
Atherton, P. (1998). Aloe vera revisited. Brit. J. Phytother. 4(4):176183.
Averbeck, B. and Reeh, P. W. (2001). Interactions of inflammatory media- 1520
tors stimulating release of calcitonin gene-related peptide substance P and
prostaglandin E-2 from isolated rat skin. Neuropharmacology 40(3):416
423.
Avila, H., Rivero, J., Herrera, F., and Fraile, G. (1997). Cytotoxicity of a low
molecular weight fraction from Aloe vera (Aloe barbadensis Miller) gel. 1525
Toxicon 35(9):14231430.
Bautista-Perez, R., Segura-Cobos, D., and Vazquez-Cruz, B. (2004). In vitro antibradykinin activity of Aloe barbadensis gel. J. Ethnopharmacol. 93(1):89
92.
Beppu, H., Koike, T., Shimpo, K., Chihara, T., Hoshino, M., Ida, C., and Kuzuya, 1530
H. (2003). Radical-scavenging effects of Aloe arborescens Miller on prevention of pancreatic islet B-cell destruction in rats. J. Ethnopharmacol. 89:37
45.
Beppu, H., Kwai, K., Shimpo, K., Chihara, T., Tamai, I., Ida, C., Ueda, M.,
and Kuzuya, H. (2004). Studies on the components of Aloe arborescens from 1535
Japan monthly variation and differences due to part and position of the leaf.
Biochem. Syst. Ecol. 32:783795.
Beppu, H., Nagamura, Y., and Fujita, K. (1993). Hypoglycemic and antidiabetic
effects of Aloe arborescens Miller var. natalensis Berger. Phytother. Res. 7:
S37S42.
1540
Beppu, H., Shimpo, K., Chihara, T., Tamai, I., Nomoto-Yamaji, S., Ozaki, S.,
Ito, S., and Kuzuya, H. (2006a). Inhibitory effects of aloe carboxypeptidase
fraction on streptomycin-induced enhancement of vascular permeability in
the pancreatic islets. Phytomedicine 13(12):4960.
Beppu, H., Shimpo, K., Chihara, Kaneko, T., Tamai, I., Yamaji, S., Ozaki, 1545
S., Kuzuya, H. and Sonoda, S. (2006b). Antidiabetic effects of dietary administration of Aloe arborescens Miller components on multiple low-dose
streptomycin-induced diabetes in mice: investigatioin on hypoglycemic action and systemic absorption dynamics of aloe components. J. Ethnopharmacol. 103(3)468477.
1550
Blitz, J. J., Smith, J. W., and Gerard, J. R. (1963). Aloe vera gel in peptic ulcer
therapy: preliminary report. J. Am. Osteopath. Assoc. 62:731735.
Blumenthal, M., and Milot, B. (2004). Bioassays for testing activity and bioavailability of botanical products. HerbalGram 63:4851.
December 31, 2009
2:5
FSN
BFSN_A_354613
1555
1560
1565
1570
1575
1580
1585
1590
1595
1600
1605
1610
1615
1620
Bottenberg, M. M., Wall, G. C., Harvey, R. L., and Habib, S. (2007). Oral Aloe
vera-induced hepatitis. Ann. Pharmacother. 41(10):17401943.
Bozzi, A., Perrin, C., Austin, S., Vera, F. A. (2007). Quality and authenticity of
commercial aloe vera gel powders. Food Chem. 103(1):2230.
Briggs, C. (1995). Herbal medicine: Aloe. Can. Pharm. J. 128:4850.
Buenz, E. J. (2008). Aloin induces apoptosis in Jurkat cells. Toxicol. in vitro
22(2):422429.
Bunyapraphatsara, N., Chansrakaew, W., Pornchirasilp, S., Peungvicha, P., and
Chokechaijaroenporn, O. (1995). Antidiabetic effect of fresh and preserved
aloe gel. Thai. J. Phytopharmacy 2(2):915.
Bunyapraphatsara, N., Yongchaiyudha, S., Rungpitarangsi, V., and Chokechaijaroenporn, O. (1996). Antidiabetic activity of Aloe vera juice. II Clinical
trial in diabetes mellitus patients in combination with glibenclamide. Phytomedicine 3(3):245248.
Bush, T. M., Rayburn, K. S., Holloway, S. W., Sanchez-Yamamoto, D. S.,
Allen, B. L., Lam, T. et al. (2007). Adverse interactions between herbal and
dietary substances and prescription medications: a clinical survey. Altern.
Ther. Health Med. 13:3035.
Canigueral, S., and Vila, R. (1993). Aloe. Brit. J. Phytother. 3:6775.
Cao, X. L., Huang, D. F., Dong, Y. M., Zhao, H., and Ito, Y. (2007). Separation
of aloins A and B from Aloe vera exudates by high speed countercurrent
chromatography. J. Liquid Chromatogr. Rel. Technol. 30(912):16571668.
Capasso, F., Borrelli, F., Capasso, R., Di Carlo, G., Izzo, A. A., Pinto, L.,
Mascolo, N., Castaldo, S., and Longo, R. (1998). Aloe in its therapeutic use.
Phytother. Res. 12: S124S127.
Capasso, F., Izzo, A. A., Pinto, L., Bifulco, T., Vitobello, C., and Mascolo, N.
(2000). Phytotherapy and quality of herbal medicines. Fitoterapia 71:S58
S65.
Cerqueira, L., McKnight, L. S., Rodriguez, S., and Turner, C. E. (1999). Bifurcated method to process Aloe whole leaf. US Patent 5,923,357.
Chalaprawat, M. (1997). The hypoglycaemic effects of Aloe vera in Thai diabetic
patients. J. Clin. Epidemiol. 50:3.
Chen, S. H., Lin, K. Y., Chang, C. C., Fang, C. L., and Lin, C. P. (2007). Aloeemodin-induced apoptosis in human gastric carcinoma cells. Food Chem.
Toxicol. 45(11):22962303.
Chithra, P., Sajithlal, G. B., and Chandrakasan, G. (1998a). Influence of Aloe
vera on the glycosaminoglycans in the matrix of healing dermal wounds in
rats. J. Ethnopharmacol. 59(3):179186.
Chithra, P., Sajithlal, G. B., and Chandrakasan, G. (1998b). Influence of Aloe
vera on the healing of dermal wounds in diabetic rats. J. Ethnopharmacol.
59(3):195201.
Chithra, P., Sajithlal, G. B., and Chandrakasan, G. (1998c). Influence of Aloe
vera on collagen characteristics in healing dermal wounds in rats. Mol. Cell.
Biochem. 181(12):7176.
Choi, S. W., Son, B. W., Son, Y. S., Park, Y.I., Lee, S. K. and Cheng, M. H.
(2001). The wound-healing effect of a glycoprotein fraction isolated from
Aloe vera. Brit. J. Dermatol. 145(4):535545.
Chow, J. T. N., Williamson, D. A., Yates, K. M., and Goux, W. J. (2005).
Chemical characterization of the immunomodulating polysaccharide of Aloe
vera L. Carbohyd. Res. 340(6):11311142.
Coats, B. C. (1979). Hypoallergenic stabilized Aloe vera gel. US Patent
4,178,372.
Coats, B. C. (1994). Method of processing stabilized Aloe vera gel obtained
from the whole Aloe vera leaf. US Patent 5,356,811.
Cobble, H. H. (1975). Stabilized Aloe vera gel. US Patent 3,892,853.
Committee Herbal Medicional Products (HMPC). (2007). Assessment report
on Aloe Barbadensis Miller and Aloe (various species, mainly Aloe Ferox
Miller and its hybrids). (Doc. Ref: EMEA/HMPC/76313/2006). Evaluation
of Medicines for Human Use. European Medicines Agency (EMEA), London.
Cordella, C., Moussa, I., Martel, A.-C., Sbirrazzuoli, N., and Lizzani-Cuvelier,
L. (2002). Recent developments in food characterization and adulteration
detection: Technique-oriented perspectives. J. Agric. Food Chem. 50:1751
1764.
Corsi, M.M., Bertelli, A.A., Gaja, G., Fulgenzi, A. and Ferrero, M.E. (1998).
The therapeutic potential of Aloe vera in tumor-bearing rats. Int. J. Tissue
Ract. 20:115118.
17
Danof, I. E. (1987). Aloe in cosmetics does it do anything?. Cosmet. Toiletries

102:6263.
Danof, I. E. (1993). Potential reversal of chronological and photo-aging of the
skin by topical application of natural substances. Phytother. Res. 7:S53S56.
Danof, I. E., and McAnalley, B. H. (1983). Stabilized Aloe vera - effect on 1625
human skin cells. Drug Cosmet. Ind. 133:52, 54, 105106.
Davies, P., Bailey, P. J., Goldenberg, M. M., and Fordhutchinson, A. W. (1984).
The role of arachidonic-acid oxygenation products in pain and inflammation.
Annu. Rev. Immunol. 2:335357.
Davis, R. H., Agnew, P. S., and Shapiro, E. (1986). Antiarthritic activity of 1630
anthraquinones found in Aloe for pedriatic medicine. J. Am. Podiat. Med.
Assn. 76(2):6166.
Davis, R. H., Donato, J. J., Hartman, G. M., and Haas, R. C. (1994). Antiinflammatory and wound healing activity of a growth substance in Aloe vera.
J. Am. Podiat. Med. Assn. 84(2):7781.
1635
Davis, R. H., Kabbani, J. M., and Maro, N. P. (1987). Aloe vera and wound
healing. J. Am. Podiat. Med. Assn. 77(4):165169.
Davis, R. H., Leitner, M. G., Russo, J. M., and Byrne, M. E. (1989a). Wound
healing. Oral and topical activity of Aloe vera. J. Am. Podiat. Med. Assn.
79(11):559562.
1640
Davis, R. H., Leitner, M. G., Russo, J. M., and Byrne, M. E. (1989b). Antiinflammatory activity of Aloe vera against a spectrum of irritants. J. Am.
Podiat. Med. Assn. 79(6):263276.
Davis, R. H., Rosenthal, K. Y., Cesario, L. R., and Rouw, G. A. (1989c).
Processed Aloe vera administered topically inhibits inflammation. J. Am. 1645
Podiat. Med. Assn. 79(8):395397.
De Smet, P. A. G. M. (2002). Drug therapy - Herbal remedies. N. Engl. J. Med.
347(25):20462056.
De Smet, P. A. G. M. (2004). Health risks of herbal remedies: An update. Clin.
Pharmacol. Ther. 76(1):117.
1650
Diehl, B., and Teichmuller, E. E. (1998). Aloe vera, quality inspection and
identification. Agro Food Ind. Hi-Tech 9:1416.
Dominguez-Soto, L. (1992). Photodermatitis to Aloe vera. Int. J. Dermatol.
31(5):372.
Eberendu, A. R. (2004). An industry view of the importance of assay develop- 1655
ment and validation. Inside Lab. Manag. 4(4):3.
Ernst, E. (2000). Adverse effects of herbal drugs in dermatology. Br. J. Dermatol.
143:923929.
Eshun, K., and He, Q. (2004). Aloe vera: A valuable ingredient for the food,
pharmaceutical and cosmetic industries A review. CRC Cr. Rev. Food Sci. 1660
44:9196.
Esteban, A., Zapata, J. M., Casano, L., Martn, M., and Sabater, B. (2000).
Peroxidase activity in Aloe barbadensis commercial gel: Probable role in
skin protection. Planta Med. 66(8):724727.
Esua, M. F., and Rauwald, J. W. (2006). Novel bioactive maloyl glucans from 1665
Aloe vera gel: isolation, structure elucidation and in vitro bioassays. Carbohydr. Res. 341:355364.
European Council (1988). Council Directive (EEC) No 88/388 on the approximation of the laws of the Member States relating to flavourings for use
in foodstuffs and to source materials for their production. Official J. Eur. 1670
Communities L188:6166.
European Parliament and European Council (1995). European Parliament and
European Council Directive No 95/2/EC on food additives other than colours
and sweeteners. Official J. Eur. Communities L61:140.
Federici, E., Multari, G., Callo, F. R., and Palazzino, G. (2005). Herbal drug: 1675
from traditional use to regulation. Ann. Ist. Super. Sanita 41:4951.
Femenia, A., Garca-Pascual, P., Simal, S., and Rossello, C. (2003). Effects of
heat treatment and dehydration on bioactive polysaccharide acemannan and
cell wall polymers from Aloe barbadensis Miller. Carbohyd. Polym. 51:397
405.
1680
Femenia, A., Sanchez, E. S., Simal, S., and Rossello, C. (1999). Compositional
features of polysaccharides from Aloe vera (Aloe barbadensis Miller) plant
tissues. Carbohyd. Polym. 39:109117.
Flaster, T. and Lassiter, J. (2004). Quality control in herbal preparations: using
botanical reference standards for proper identification. HerbalGram 63:32 1685
37.
December 31, 2009
18
1690
1695
1700
1705
1710
1715
1720
1725
1730
1735
1740
1745
1750
2:5
FSN
BFSN_A_354613
Fogleman, R. W., Chapdelaine, J. M., Carpenter, R. H., and McAnalley, B. H.

(1992). Toxicologic evaluation of injectable acemannan in the mouse, rat and
dog. Vet. Hum. Toxicol. 34(3):201205.
Fox, T. R. (1990). Aloe vera Revered, mysterious healer. Health Food Business,
4546.
Franz, G. (1989). Polysaccharides in pharmacy: current applications and future
concepts. Planta Med. 55:493497.
Freytag, E. (1954). Suggested role of traumatic acid in Aloe wound healing.
Pharmazie 9:705.
Frumkin, A. (1989). Aloe vera, salicylic acid and aspirin for burns. Plast. Reconstr. Surg. 83(1):196.
Fujita, K., Teradaira, R., and Nagatsu, H. (1976). Bradykininase activity of Aloe
extract. Biochem. Pharmacol. 25:205206.
Fujita, K., Ito, S., Teradaira, R., and Beppu, H. (1979). Properties of a carboxypeptidase from aloe. Biochem. Pharmacol. 28:12611262.
Fulton, J. F. Jr. (1990). The stimulation of postdermabrasion wound healing
with stabilized Aloe vera gel-polyethylene oxide dressing. J. Dermatol. Surg.
Onc. 16(5):460467.
Garifallidi, P., Hiskia, A., and Calokerinos, A. C. (2004). Determination of adulteration in Aloe vera comercial products. In:4th Aegean Analytical Chemistry
Days, Kusadasi, Turkey.
Ghannam, N., Kingston, M., Al-Meshaal, I. A., Tariq, M., Parman, N. S., and
Woodhouse, N. (1986). The antidiabetic activity of aloes: Preliminary clinical
and experimental observations. Horm. Res. 24:288294.
Gjerstad, G. (1971). Chemical studies of Aloe vera juice. I: Amino acid analysis.
Advancing Frontiers Plant Sci. 28:311315.
Gowda, D. C. (1980). Structural studies of polysaccharides from Aloe saponaria
and Aloe vanbalenii. Carbohyd. Res. 83:402405.
Gowda, D. C., Neelisiddaiah, B., and Anjaneyalu, Y. V. (1979). Structural studies
of polysaccharides from Aloe vera. Carbohyd. Res. 72:201205.
Griggs, B. (1996). Aloe, aloe. Country Living, 122124.
Grindlay, D., and Reynolds, T. (1986). The Aloe vera phenomenon: a review of
the properties and modern uses of the leaf parenchyma gel. J. Ethnopharmacol. 16(23):117151.
Gutterman, Y., and Chauser-Volfson, E. (2000). The distribution of the phenolic
metabolites barbaloin, aloeresin and aloenin as a peripheral defense strategy in
the succulent leaf parts of Aloe arborescens. Biochem. Syst. Ecol. 28(9):825
838.
Haddad, P., Samsami, S., Ali Oghabian, M., Amouzgar-Hashemi, F., and Tigmaghz, Z. (2007). A clinical trial of Aloe vera for prophylaxis of radiationinduced dermatitis. Radiother. Oncol. 84:S81S81.
Hale, G. (2003). Scope of products containing aloe has broadened. International
Aloe Science Council Website (http://www.iasc.org/productscope.html).
He, Q., Changhong, L., Kojo, E., and Tian, Z. (2005). Quality and safety
assurance in the processing of aloe vera gel juice. Food Control 16:95
104.
Heggers, J. P., Kucukcelebi, A., Listengarten, D., Stabenau, J., Ko, F., Broemeling, L. D., Robson, M. C., and Winters, W. D. (1996). Beneficial effect of
Aloe on wound healing in an excisional wound model. J. Altern. Complem.
Med. 2(2):271277.
Heggers, J. P., Kucukcelebi, A., Stabenau, C. J., Ko, F., Broemeling, L. D.,
Robson, M. C., and Winters, W. D. (1995). Wound healing effects of Aloe gel
and other topical antibacterial agents on rat skin. Phytother. Res. 9:455457.
Heggers, J.P., Pelley, R.P., and Robson, M.C. (1993). Beneficial effects of Aloe
in wound healing. Phytother. Res. 7:S48S52.
Heggie, S., Bryant, G. P., Tripcony, L., Keller, J., Rose, P., Glendennig, M., and
Heath, J. (2002). A Phase III study on the efficacy of topical Aloe vera gel on
irradiated breast tissue. Cancer Nurs. 25(6):442451.
Herlihy, J. T., Kim, J. D., Kalu, D. N., Nelson, J. F., Ward, W. F., Ikeno, Y., and
Yu, B. P. (1998). Effects of Aloe vera ingestion in the rat. II. Hormonal and
metabolic characteristics. Phytother. Res. 12(5):355360.
Hogan, D. J. (1988). Widespread dermatitis after topical treatment of chronic
leg ulcers and statis dermatitis. Can. Med. Assoc. J. 138(4):336338.
Hu, Q. H., Hu, Y., and Xu, J. (2005). Free radical-scavenging activity of Aloe vera
(Aloe barbadensis Miller) extracts by supercritical carbon dioxide extraction.
Food Chem. 91(1):8590.
Hu, Y., Xu, J., and Hu, Q. (2003). Evaluation of antioxidant potential of Aloe
vera (Aloe barbadensis Miller) extracts. J. Agric. Food Chem. 51(26):7788
1755
7791.
Hunter, D., and Frumkin, A. (1991). Adverse reactions to vitamin E and Aloe
vera preparations after dermabrasion and chemical peel. Cutis 47(3):193
196.
Hutter, J. A., Salman, M., Stavinoha, W. B., Satsangi, N., Williams, R. F.,
Streeper, R. T., and Weintraub, S. T. (1996). Antiinflammatory C-glucosyl 1760
chromone from Aloe barbadensis. J. Nat. Prod. 59(5):541543.
Ikeno, Y., Cox, R. J., Uchida, K., and Reddick, R. L. (1998). Immunohistochemical analysis of lipid peroxidation products and glycated endproducts
in aging fischer 344 rat kidneys and modulation by dietary restriction. Free
Radical Bio. Med. 25:S84.
1765
Ikeno, Y., Hubbard, G. B., Lee, S., Yu, B. P., and Herlihy, J. T. (2002). The
influence of long-term Aloe vera ingestion on age-related disease in male
Fischer 344 rats. Phytother. Res. 16(8):712718.
Im, S. A., Oh, S. T., Song, S., Kim, M. R., Kim, D. S., Woo, S. S., Jo, T. H.,
Park, Y. I., and Lee, C. K. (2005). Identification of optimal molecular size of 1770
modified Aloe polysaccharides with maximum immunomodulatory activity.
Int. J. Immunopharmaco. 5(2):271279.
Imanishi, K., and Suzuki, I. (1984). Augmentation of natural cell-mediated cytotoxic reactivity of mouse lymphoid cells by Aloctin A. Int. J. Immunopharmaco. 6:539543.
1775
Imanishi, K., Ishiguro, T., Saito, H., and Suzuki, I. (1981). Pharmacological
studies on a plant lectin, Aloctin A. Part I. Growth inhibition of mouse methylcholanthrene induced fibrosarcoma (Meth A) in ascites form by Aloctin A.
Experientia 37(11):11861187.
International Aloe Science Council (IASC). (2004). Aloe vera cer- 1780
tification criteria. International Aloe Science Council Website
(http://www.iasc.org/certcriteria.html).
Ishii, Y., Tanizawa, H., and Takino, Y. (1990). Studies of Aloe III. Mechanism
of cathartic effect. (2). Chem. Pharm. Bull. 38(1):197200.
Kar, A., Panda, S., and Bharti, S. (2002). Relative efficacy of three medicinal 1785
plant extracts in the alteration of thyroid hormone concentrations in male
mice. J. Ethnopharmacol. 81(2):281285.
Kaufman, T., Kalderon, N., Ullman, Y., and Berger, J. (1988). Aloe vera gel
hindered wound healing of experimental second-degree burns: A quantitative
controlled study. J. Burn Care Rehabil. 9(2):156159.
1790
Kim, H. S., and Lee, B. M. (1997). Inhibition of benzo[a]pyrene DNA adduct
formation by Aloe barbadensis Miller. Carcinogenesis 18(4):771776.
Kim, H. S., Kacew, S., and Lee, B. M. (1999). In vitro chemopreventive effect of
plant polysaccharides (Aloe barbadensis Miller, Lentinis edodes, Ganoderma
lucidum and Coriolus versicolor). Carcinogenesis 20(8):16371640.
1795
Kim, K.H., Lee, J.G, Kim, D.C., Kim, M.K., Park, J.H., Shin, Y.G., Lee, S.K.,
Jo, T.H., and Oh, S.T. (1998). The development of a new method to detect the
adulteration of commercial Aloe gel powders. Arch. Pharm. Res. 21(5):514
520.
Klein, A. D., and Penneys, N. S. (1988). Aloe vera. J. Am. Acad. Dermatol. 1800
18(4):714720.
Kodym, A. (1991). The main chemical component contained in fresh leaves
and in a dry extract from three years old Aloe arborescens Mill. grown in
hothouses. Pharmazie 46:216219.
Kodym, A., Marcinkowski, A., and Kukula, H. (2003). Technology of eye drops 1805
containing aloe (Aloe arborescens Mill.Liliaceae) and eye drops containing
both aloe and neomycin sulphate. Acta Pol. Pharm. 60(1):319.
Koike, T., Beppu, H., Kuzuya, H., Maruta, K., Shimpo, K., Suzuki, M., Titani,
K., and Fujita, K. (1995). A 35 kDa mannose-binding lectin with hemagglutinating and mitogenic activities from Kidachi Aloe (Aloe arborescens 1810
Miller var. natalensis Berger). J. Biochem. 118(6):12051210.
Koo, M. W. L. (1994). Aloe vera: antiulcer and antidiabetic effects. Phytother.
Res. 8:461464.
Kupchan, S. M., and Karim, A. (1976). Tumor inhibitor. 114. Aloe emodin:
antileukemic principle isolated from Rhamnus frangula L. Lloydia 39(4):223 1815
224.
Lachenmeier, K., Kuepper, U., Musshoff, F., Madea, B., Reusch, H.,
and Lachenmeier, D. W. (2005). Quality control of Aloe vera
December 31, 2009
2:5
FSN
BFSN_A_354613
1820
1825
1830
1835
1840
1845
1850
1855
1860
1865
1870
1875
1880
Q8
beverages. Electronic J. Environ. Agric. Food Chem. 4(4):112.

http://ejeafche.uvigo.es/4(4)2005/010442005F.htm.
Langmead, L., Makins, R. J., and Rampton, D. S. (2004). Anti-inflammatory
effects of Aloe vera gel in human colorectal mucosa in vitro. Aliment. Pharmacol. Ther. 19:521527.
Lawless, J., and Allan, J. (2000). Aloe vera Natural wonder cure. Harper
Collins Publihers, Hammersmith, London.
Lee, A., Chui, P. T., Aun, C. S. T., Gin, T., and La, A. S. C. (2004). Possible interaction between sevoflurane and Aloe vera. Ann. Pharmacother.
38(10):16511654.
Lee, B. M., and Park, K.-K. (2003). Beneficial and adverse effects of chemopreventive agents. Mutat. Res. 523524:265278.
Lee, K. Y., Weintraub, S. T., and Yu, B. P. (2000). Isolation and identification
of a phenolic antioxidany from Aloe barbadensis. Free Radical Bio. Med.
28(2):261265.
Lee, M. J., Lee, O. H., Yoon, S. H., Lee, S. K., Chung, M. H., Park, Y. I., Sung,
C. K, Choi, J. S., and Kim, K. W. (1998). In vitro angiogenic activity of Aloe
vera gel on calf pulmonary artery endothelial (CPAE) cell. Arch. Pharm. Res.
21(3):260265.
Leung, A. Y. (1977). Aloe vera in cosmetics. Drug Cosmet. Ind. 120(6):34.
Leung, M. Y. K., Liu C., Zhu, L. F., Hui, Y. Z., Yu, B., and Fung, K. P. (2004).
Chemical and biological characterization of a polysaccharide biological response modifier from Aloe vera L. var. chinensis (Haw.) Berg. Glycobiology
14(6):501510.
Li, H. M., Su, L. H., and Chen, R. Z. (2004). Simultaneous determination of trace
amounts of iron (II), copper (II) and cobalt (II) in aloe by second derivative
peak area spectrophotometry. Spectrosc. Spect. Anal. 24(4):463465.
Li, J. Y., Wang, T. X., Shen, Z. G., and Hu, Z. H. (2003). Relationship between
leaf structure and aloin content in six species of Aloe L. Acta Bot. Sin.
45(5):594600.
Lim, B. O., Seong, N. S., Choue, R. W., Kim, J. D., Lee, H. Y., Kim, S. Y.,
Yu, B. P., Jeon, T. I., and Park, D. K. (2003). Efficacy of dietary Aloe vera
supplementation on hepatic cholesterol and oxidative status in aged rats. J.
Nutr. Sci. Vitaminol. 49(4):292296.
Liu, C. H., Wang, C. H., Xu, Z. L., and Wang, Y. (2007). Isolation, chemical
characterization and antioxidant activities of two polysaccharides from the
gel and the skin of Aloe barbadensis Miller irrigated with sea water. Proc.
Biochem. 42(6):961970.
Loots, D. T., van der Westhuizen, F. H., and Botes, L. (2007). Aloe ferox leaf gel
phytochemical content, antioxidant capacity, and possible health benefits. J.
Agric. Food Chem. 55(17):68916896.
Luta, G., and McAnalley, B. H. (2005). Aloe vera: Chemical composition and
methods used to determine its presence in comercial products. Glycoscience
and Nutrition 6(4):112.
Luyckx, V. A., Ballantine, R., Claeys, M., Cuyckens, F., van den Heuvel, H.,
and Cimanga, R. K., Vlietinck, A. J., De Broe M. E., Katz, I. J. (2002). Herbal
remedy-associated acute renal failure secondary to Cape aloes. Am. J. Kidney
Dis. 39(3):E13.
Mabusela, W. T., Stephen, A. M., and Botha, M. C. (1990). Carbohyd. Polym.
from Aloe ferox leaves. Phytochemistry 29:35553558.
Maenthaisong, R., Chaiyakunapruk, N., Niruntraporn, S. and Kongkaew, C.
(2007). The efficacy of Aloe vera used for burn wound healing: A systematic
review. Burns 33:713718.
Mandal, G., and Das, A. (1980). Structure of the glucomannan isolated from
Aloe barbadensis Miller. Carbohyd. Res. 87:249256.
Manna, S., and McAnalley, B. H. (1993). Determination of the position of the
O-acetyl group in a beta (14) mannan (Acemannan) from Aloe barbadensis
Miller. Carbohyd. Res. 17(241):317319.
Marshall, G. D., and Druck, J. P. (1993). In vitro stimulation of NK activity by
Acemannan. J. Immunol. 150:241A.
Marshall, G. D., Gibbon, A. S., and Parnell, L.S. (1993). Human cytokines
induced by Acemannan. J. Allergy Clin. Immun. 91:241A.
Marshall, J. M. (1990). Aloe vera gel: what is the evidence? Pharm. J., 360
362.
McAnalley, B. H. (1988). Process for preparation of Aloe products, produced
thereby and composition thereof. US Patent 4,735,935.
19
McAnalley, B. H. (1990). Process for preparation of Aloe products. US Patent 1885

No. 4,957,907.
McAuliffe, J. C., and Hindsgaul, O. (1997). Carbohydrate drugs-an ongoing
challenge. Chem. Ind., 170174.
McCauley, R. L., Heggers, J. P., and Robson, M. C. (1990). Frostbite. Methods
to minimize tissue loss. Postgrad. Med. 88(8):6768, 7377.
1890
McConaughy, S. D., Stroud, P. A., Boudreaux, B., Hester, R. D., and McCormick, C. L. (2008). Structural characterization and solution properties
of galacturonate polysaccharide derived from Aloe vera capable of in situ
gelation. Biomacromolecules 9:472480.
McDaniel, H. R. (1987). A clinical pilot study using Carrsyn (Aloe vera con- 1895
centrate) in the treatment of AIDS patients. Am. J. Clin. Pathol. 88:68.
McDaniel, H. R., Perkins, S., and McAnalley, B. H. (1987). A clinical pilot
study using Carrsyn in the treatment of aquired immunodeficiency syndrome
(AIDS). Am. J. Clin. Pathol. 88:534.
McKeown, E. (1987). Aloe vera. Cosmet. Toiletries 102:6465.
1900
McKeown, E. C. (1983). Aloe Vera The quest for the curative missing link.
Drug Cosmet. Ind., 3233.
Meadows, T. P. (1980). Aloe as a humectant in new skin preparations. Cosmet.
Toiletries 95(11):5156.
Merriam, E. A., Campbell, B. D., Flood, L. P., Welsh, C. J. R., McDaniel, H. 1905
R., and Busbee, D. L. (1996). Enhancement of immune function in rodents
using a complex plant carbohydrate which stimulates macrophage secretion
of immunoreactive cytokines. In: Advances in Anti-Aging Medicine. Vol.
1, pp. 181203. Klatz, R. M., Ed. Mary Ann Liebert, Inc., Larchmont, New
York.
1910
Montaner, J. K., Gill, J., Singer, J., Raboud, J., Arseneau, R., McLean, B. D.,
Schechter, M. T., and Ruedy, J. (1996). Double blind placebo-controlled pilot
trial of Acemannan in advanced human immunodeficiency virus disease. J.
Acq. Immun. Def. Synd. 12, 153157.
Moon, E.-J., Lee, Y. M., Lee, O.-H., Lee, M.-J., Lee, S.-K., Chung, M.-H., Park, 1915
Y.-I., Sung, C.-K., Choi, J.-S., and Kim, K.-W. (1999). A novel angiogenic
factor derived from Aloe vera gel:-sitosterol, a plant sterol. Angiogenesis
3(2):117123.
Morton, J. F. (1961). Folk uses and commercial exploitation of Aloe leaf pulp.
Econ. Bot. 15:311319.
1920
Mossa, J. S. (1985). A study on the crude antidiabetic drugs used in Arabian
folk medicine. Int. J. Crude Drug Res. 23:137145.
Mueller, S. O., and Stopper, H. (1999). Characterization of the genotoxicity of
anthraquinones in mammalian cells. Biochim. Biophys. Acta 1428(23):406
414.
1925
Mueller, S. O., Stopper, H., and Dekant, W. (1998). Biotransformation of the anthraquinones emodin and chrysophanol by cytochrome P450 enzymes. Bioactivation to genotoxic metabolites. Drug Metab. Dispos. 26(6):540546.
Natow, A. J. (1986). Aloe vera, fiction or fact. Cutis 37(2):106108.
Newton, L. E. (1987). On the suitability of Kenyan aloes for commercial culti- 1930
vation. East Africa Nat. Hist. Soc. Bull. 17:58.
Ni, Y., Turner, D., Yates, K. M., and Tizard, I. (2004). Isolation and characterization of structural components of Aloe vera L. leaf pulp. Int. Immunopharmacol. 4(14):17451755.
Niciforovic, A., Adzic, M., Spasic, S. D., and Radojcic, M. B. (2007). Antitumor 1935
effects of a natural anthracycline analog (Aloin) involve altered activity of
antioxidant enzymes in HeLaS3 cells. Cancer Biol. Ther. 6(8):12001205.
Northway, R. B. (1975). Experimental uses of Aloe vera extract in clinical
practice. Vet. Med. Sm. Anim. Clin. 70(1):89.
Norton, S. J., Talesa, V., Yuan, W. J., and Principato, G. B. (1990). Glyox- 1940
alase I and glyoxalase II from Aloe vera: purification, characterization and
comparison with animal glyoxalases. Biochem. Int. 22(3):411418.
Okamura, N., Asai, M., Hine, N., and Yagi, A. (1996). High-performance liquid
chromatographic determination of phenolic compounds in Aloe species. J.
Chromatogr. A 746:225231.
1945
Okyar, A., Can, A., Akev, N., Baktir, G., and Sutlupinar, N. (2001). Effect of
Aloe vera leaves on blood glucose level in type I and type II diabetic rat
models. Phytother. Res. 15(2):157161.
Ovodova, R. G., Lapchik, V. F., and Ovodov, Y. S. (1975). Polysaccharides in
Aloe arborescens. Khim. Prir. Soedin. 11:35.
1950
December 31, 2009
20
1955
1960
1965
1970
1975
1980
1985
1990
1995
2000
2005
2010
2015
2:5
FSN
BFSN_A_354613
Paez, A., Gebre, G. M., Gonzalez, M. E., and Tschaplinski, T. J. (2000). Growth,
soluble carbohydrates, and aloin concentration of Aloe vera plants exposed
to three irradiance levels. Environ. Exp. Bot. 44(2):133139.
Park, M. K., Park, J. H., Kim, N. Y., Shin, Y. G., Choi, Y. S., Lee, J. G., Kim,
K. H., and Lee, S. K. (1998). Analysis of 13 phenolic compounds in aloe
species by high performance liquid chromatography. Phytochem. Analysis
9(4):186191.
Paulsen, B. S., Fagerheim, E., and Overbye, E. (1978). Structural studies of
the polysaccharides from Aloe plicatilis Miller. Carbohyd. Res. 60:345
351.
Payne, J. M. (1970). Tissue response to Aloe vera gel following periodontal
surgery. Thesis submitted to Faculty of Baylor University for the Degree of
Master of Science.
Pecere, T., Gazzola, M. V., Mucignat, C., Parolin, C., Vecchia, F. D., Cavaggioni,
A., Basso, G., Diaspro, A., Salvato, B., Carli, M., and Palu, G. (2000). Aloeemodin is a new type of anti-cancer agent with selective activity against
neuroectodermal tumors. Cancer Res. 60(11):28002804.
Pelley, R. P. (1992). Aloe quality control: current of HPLC in the quality control
of aloe barbadensis extracts, Aloe Today, (Autumn), 1926.
Pelley, R. P., Wang, Y.-T., and Waller, T. A. (1993). Current status of quality
control of Aloe barbadensis extracts. SOFW Journal 25(1):255268.
Pelley, R. P., Martini, W. J., Liu, D. Q., Yang, Z., Rachui, S., Li, K. M., Waller,
T. A., and Strickland, F. M. (1998). Multiparameter analysis of commercial
Aloe vera materials and comparison of Aloe barbadensis Miller extracts.
Subtrop. Plant Sci. 50:114.
Penneys, N. S. (1982). Inhibition of arachidonic acid oxidation in vitro by
vehicle components. Acta Derm.-Venereol. 62:5961.
Perez, Y. Y., Jimenez-Ferrer, E., Zamilpa, A., Hernandez-Valencia, M., AlarconAguilar, F. J., Tortoriello, J., and Roman-Ramos, R. (2007). Effect of
polyphenol-rich extract from Aloe vera gel on experimentally induced insulin resistance in mice. Am. J. Chin. Med. 36(6):10371046.
Pugh, N., Ross, S. A., ElSohly, M. A., and Pasco, D. S. (2001). Characterization
of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera
with potent immunostimulatory activity. J. Agric. Food Chem. 49(1):1030
1034.
Qiu, Z., Jones, K., Wylie, M., Jia, Q., and Orndorff, S. (2000). Modified Aloe
barbadensis polysaccharide with inmunoregulatory activity. Planta Med.
66(2):152156.
Rabe, C., Musch, A., Schirmacher, P., Kruis, W., and Hoffmann, R. (2005).
Acute hepatitis induced by an Aloe vera preparation: A case report. World J.
Gastroenterol.,11(2):303304.
Rajasekaran, S., Sivagnanam, K., and Subramanian, S. (2005). Mineral contents
of Aloe vera leaf gel and their role on streptozotocin-induced diabetic rats.
Biol. Trace Elem. Res. 108(13):185196.
Ralamboranto, L., Rakotovao, L. H., Le Deaut, J. Y., Chaussoux, D., Salomon,
J. C., Fournet, B., Montreuil, J., Rakotonirina-Randriambeloma, P. J., Dulat,
C., and Coulanges, P. (1982). Immunomodulating properties of an extract
isolated and partially purified from Aloe vahombe. 3. Study of antitumoral
properties and contribution to the chemical nature active principle. Arch. Inst.
Pasteur Madagascar 50(1):227256.
Rebecca, W., Kayser, O., Hagels, H., Zessin, K.-H., Madundo, M., and Gamba,
N. (2003). The phytochemical profile and identification of main phenolic
compounds from the leaf exudate of Aloe secundiflora by high-performance
liquid chromatography-mass spectrometry. Phytochem. Analysis 14(2):83
86.
Reglamento (CE) No 258/1997, de 27 de enero (DOCE L 43, de 14 de febrero),
sobre nuevos alimentos y nuevos ingredientes alimentarios. Ministerio de
Agricultura Pesca y Alimentacion. Subdireccion General de Planificacion
Alimentaria.
Reif, K., Sievers, H., and Steffen, J.-P. (2004). The role of chemical reference
standards as analytical tools in the quality assessment of botanical materials
An European perspective. HerbalGram 63:3843.
Reynolds, T. (1985). The compounds of Aloe leaf exudates: a review. Bot. J.
Linn. Soc. 90:15777.
Reynolds, T. (1998). Aloe vera: what are the active ingredients? Proceeding of
the Active Ingredients Conference. pp. 8593. Paris.
Reynolds, T., and Dweck, A. C. (1999). Aloe vera leaf: a review update. J.
Ethnopharmacol. 68(13):337.
Robson, M. C., Heggers, J. P., and Hagstrom, W. J. (1982). Myth, magic,
withchcraft or fact? Aloe vera revisited. J. Burn Care Rehabil. 3:157163. 2020
Rodriguez, S. (2004). How large is the aloe market? International Aloe Science
Council Website (http://www.iasc.org/aloemarket.html).
Rodrguez-Fragoso, L., Reyes-Esparza, J., Burchiel, S. W., Herrera-Ruiz, D.,
and Torres, E. (2008). Risks and benefits of commonly used herbal medicines
in Mexico. Toxicol. Appl. Pharmacol. 227:125135.
2025
Roman-Ramos, R., Flores-Saenz, J. L., Partida-Hernandez, G., Lara-Lemus,
A., and Alarcon-Aguilar, F. (1991). Experimental study of the hypoglycemic
effect of some antidiabetic plants. Arch. Invest. Med. 22(1):8793.
Rosca-Casian, O., Parvu, M., Vlase, L., and Tamas, M. (2007). Antifungal
activity of Aloe vera leaves. Fitoterapia 78:219222.
2030
Ross, S. A., ElSohly, M. A., and Wilkins, S. P. (1997). Quantitative analysis of
Aloe vera mucilaginous polysaccharide in commercial Aloe vera products. J.
AOAC Int. 80(2):455457.
Rubel, B. L. (1983). Possible mechanisms of the healing actions of aloe gel.
Cosmet. Toiletries 98:109114.
2035
Sabeh, F., Wright, T., and Norton, S. J. (1993). Purification and characterization of a glutathione-peroxidase from the Aloe vera plant. Enzyme Protein
47(2):9298.
Sabeh, F., Wright, T., and Norton, S. J. (1996). Isozymes of superoxide dismutase
from Aloe vera. Enzyme Protein 49(4):212221.
2040
Saccù, D., Bogoni, P., and Procida, G. (2001). Aloe exudate: Characterization by reversed phase HPLC and headspace GC-MS. J. Agric. Food Chem.
49(10):45264530.
Sahito, S. R., Kazi, T. G., Kazi, G. H., Memon, M. A., Shaikh, Q., Jakhrani,
M. A., and Shar, G. Q. (2003). Comparison of sample preparation methods 2045
for the determination of essential and toxic elements in important indigenous
medicinal plant Aloe barbadensis. J. Chem. Soc. Pakistan 25(3):201205.
Saito, H. (1993). Purification and active substances of Aloe arborescens Miller
and their biological and pharmacological activity. Phytother. Res. 7:S14S19.
Saito, H., Ishiguro, T., Imanishi, K., and Suzuki, I. (1982). Pharmacological 2050
studies on a plant lectin Aloctin A. II. Inhibitory effect of Aloctin A on
experimental models of inflammation in rats. Jpn. J. Pharmacol. 32(1):139
142.
Sakai, R. (1989). Epidemiologic survey on lung cancer with respect to cigarette
smoking and plant diet. Jpn. J. Cancer Res. 80(6):513520.
2055
Schechter, S. R. (1994). Aloe vera: the healing plant. Health Foods Business,
2324.
Schorkhuber, M., Richter, M., Dutter, A., Sontag, G., and Marian, B. (1998).
Effect of anthraquinonelaxatives on the proliferation and urokinase secretion of normal, premalignant and malignant colonic epithelial cells. Eur. J. 2060
Cancer 34(7):10911098.
Segal, A., Taylor, J. A., and Eoff, J. C. (1968). A re-investigation of polysaccharide material form Aloe vera mucilage. Lloydia 31:423424.
Shahnaz, A. M. A., Kalhonoz, Z., and Badar, Y. (1993). Aloe a biologically
active and potencial medicinal plant. Hamdard Medicus 36(1):108115.
2065
Shapiro, K., and Gong, W. C. (2002). Natural products used for diabetes. J. Am.
Pharm. Assoc. 42:217226.
Shaw, D., Leon, C., Kolev, S., and Murray, V. (1997). Traditional remedies and
food supplements: a 5 year toxicological study (19911995). Drug Safety
17:342356.
2070
Shelton, R. M. (1991). Aloe vera. Its chemical and therapeutic properties. Int.
J. Dermatol. 30(10):679683.
Shoji, A. (1982). Contact dermatitis to Aloe arborescens. Contact Dermatitis
8:164167.
Silano, M., De Vicenzi, M., De Vicenzi, A., and Silano, V. (2004). The new 2075
European legislation on tradicional herbal medicines: man features and perspectivas. Fitoterapia 75:107116.
Simal, S., Femena, A., Llull, P., and Rossello, C. (2000). Dehydration of Aloe
vera: simulation of drying curves and evaluation of functional properties. J.
2080
Food Eng. 43:109114.
Spoerke, D. G., and Elkins, B. R. (1980). Aloe vera-fact or quackery. Vet. Hum.
Toxicol. 22(6):418424.
December 31, 2009
2:5
FSN
BFSN_A_354613
2085
2090
2095
2100
2105
2110
2115
2120
2125
2130
2135
2140
2145
Steemkamp, V., and Stewart, M. J. (2007). Medical applications and toxicological activities of Aloe products. Pharm. Biol. 45(5):411420.
Strickland, F. M., Muller, H. K., Stephens, L. C., Bucana, C. D., Donawho, C. K.,
Sun, Y., and Pelley, R. P. (2000). Induction of primary cutaneous melanomas
in C3H mice by combined treatment with ultraviolet radiation, ethanol and
aloe emodin. Photochem. Photobiol. 72(3):407414.
Su, H. Y., Cherng, S. H., Chen, C. C., and Lee, H. (1995). Emodin inhibits
the mutagenicity and DNA adducts induced by 1-nitropyrene. Mutat. Res.
329(2):205212.
Sultana, B., and Anwar, F. (2008). Flavonols (kaempeferol, quercetin, myricetin)
contents of selected fruits, vegetables and medicinal plants. Food Chem.
108:879884.
Suvitayavat, W., Sumrongkit, C., Thirawarapan, S. S., and Bunyapraphatsara, N.
(2004). Effects of Aloe preparation on the histamine-induced gastric secretion
in rats. J. Ethnopharmacol. 90(23):239247.
Suzuki, I., Saito, H., Inoue, S., Migita, S., and Takahashi, T. (1979). Purification
and characterization of 2 lectins from Aloe-Arborescens Mill. J. Biochem.
85(1):163171.
Syed, T. A., Ahmad, S. A., Holt, A. H., Ahmad, S. H., Ahmad, S. H., and
Afzal, M. (1996). Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-cotrolled, double-blind study. Trop. Med. Int.
Health 1(4):505509.
tHart, L. A., van den Berg, A. J., Kuis, L., van Dijk, H., and Labadie, R. P.
(1989). An anti-complementary polysaccharide with immunological adjuvant
activity from the leaf parenchyma gel of Aloe vera. Planta Med. 55(6):509
512.
Takeyama, E., Fukushima, M., and Tanimura, A. (2002). Effect of heat-treatment
on the content and polysaccharide composition of dietary fiber. Food Sci.
Technol. Res. 8(2):125130.
Talmadge, J., Chavez, J., Jacobs, L., Munger, C., Chinnah, T., Chow, J. T.,
Williamson, D., and Yates, K. (2004). Fraction of Aloe vera L. inner gel,
purification and molecular profiling of activity. Int. J. Immunopharmaco.
4(14):17571773.
Tizard, I., Carpenter, R. H., McAnalley, B. H., and Kemp, M. (1989). The biological activity of mannans andrelated complex carbohydrates. Mol. Biother.
1:290296.
Tsuda, H., Ito, M., Hirono, I., Hawai, K., Beppu, H., Fujita, K., and Nagao, M.
(1993). Inhibitory effect of Aloe arborescens Miller var. natalensis Berger
(Kidachi aloe) on induction of preneoplastic focal lesions in the rat liver.
Phytother. Res., Suppl. 7:4347.
Umano, K., Nakahara, K., Shoji, A., and Shibamoto, T. (1999). Aroma chemicals
isolated and identified from leaves of Aloe arborescens Mill. var. natalensis
Berger. J. Agric. Food Chem. 47(9):37023705.
Urch, D. (1999). Aloe vera Natures gift. pp. 713. Blackdown Publications,
Bristol, England.
Valverde, J. M., Valero, D., Martnez-Romero, D., Guillen, F., Castillo, S., and
Serrano, M. (2004). Novel edible coating base don Aloe vera gel to maintain
table grape quality and safety. J. Agric. Food Chem. 53(20):78077813.
Van Wyk, B. E., van Oudtshoorn, B., and Gericke, N. (1997). Medicinal plants
of South Africa. Briza Publications, Pretoria.
Van Wyk, B. E., van Rheede van Oudshoorn, M. C. B., and Smith, G. F. (1995).
Geographical variation in the major compounds of Aloe ferox leaf exudate.
Planta Med. 61(3):250253.
Viljoen, A. M., Van Wyk, B.-E., and Newton, L. E. (2001). The occurrence and
taxonomic distribution of the anthrones aloin, aloinoside and microdontin in
Aloe. Biochem. Syst. Ecol. 29(1):5367.
Vogler, B. K., and Ernst, E. (1999). Aloe vera: a systematic review of its clinical
effectiveness. Brit. J. Gen. Pract. 49(447):823828.
Wagar, W. A., Shaukat, S., and Sohalil, T. (2008). Study of glibenclamide with
some traditional herbs used for the treatment of diabetes in Pakistan. J. Chem.
Soc. Pakistan,30(1):147154.
Waller, G. R., Mangiafico, S., and Ritchey, C. R. (1978). A chemical investigation of Aloe barbadensis Miller. Proc. Okla. Acad. Sci. 58:6976.
Wang, D. X., Yang, G. L., Wang, L. Y., and Song, X. R. (2000). Determination
of the active components in Clinese herb Aloe vera L. var. chinensis (Haw.)
Berger by capillary zone electrophoresis. Se Pu 18(5):423425.
21
Wang, W., Cuyckens, F., Van den Heuvel, H., Apers, S., Pieters, L., Steenkamp,
V., Stewart, M.J., Luyckx, V.A., and Claeys, M. (2003). Structural character- 2150
ization of chromone C-glucosides in a toxic herbal remedy. Rapid Commun.
Mass Spectrom. 17(1):4955.
Wang, Y. T. (1993). Bases of Aloe certification. Aloe Today,Winter:2729.
Wang, Y. T., and Strong, K. J. (1993). Monitoring physical and chemicalproperties of freshly harvested field-grown Aloe vera leaves A preliminary 2155
report. Phytother. Res. 7:S1S4.
Wang, Y. T., and Strong, K. J. (1995). Two-year study monitoring several physical and chemical properties of field-grown Aloe barbadensis Miller leaves.
Subtrop. Plant Sci. 47:3438.
Wang, Y. T. (2007). Severity of leaf harvest, supplemental nutrients, and sulphur 2160
application on long-term leaf production of Aloe barbadensis miller. Hortsci.
42(7):15841588.
Watson, J. B. (1983). Aloe. Fairchild Trop. Gard. Bull. 38:2428.
Westendorf, J., Marquardt, H., Poginskiy, B., Dominiak, M., Schmidt, J.,
and Marquardt, H. (1990). Genotoxicity of naturally occurring hydroxyan- 2165
thraquinones. Mutat. Res. 240(1):112.
Winters, W. D. (1991). Lymphocyte stimulation by newly identified Aloe lectinmitogens. Adv. New Drug Develop., 391397.
Q9
Winters, W. D. (1993). Immunoreactive lectins in leaf gel from Aloe barbadensis
Miller. Phytother. Res. 7: S23-S25.
2170
Winters, W. D., and Yang, P. B. (1996). Polypeptides of the three major medicinal
aloes. Phytother. Res. 10:573576.
Winters, W. D., Benavides, R., and Clouse, W. J., (1981). Effects of aloe extracts
on human normal and tumor cells in vitro. Econ. Bot. 35:8995.
Wolfle, D., Schumutte, C., Westendorf, J., and Marquardt, H. (1990). Hydrox- 2175
yanthraquinones as tumor promoters: enhancement of malignant transformation of C3H mouse fibroblasts and growth stimulation of primary rat
hepatocytes. Cancer Res. 50(20):65406544.
Yagi, A., and Takeo, S. (2003). Antiinflamatory constituents, aloesin and aloemannan in Aloe species and effects of tanshion VI in Salvia miltiorrhiza on 2180
heart. Yakugaku Zasshi 123(7):517532.
Yagi, A., Egusa, T., Arase, M., Tanabe, M., and Tsuji, H. (1997). Isolation and
characterization of the glycoprotein with a proliferation promoting activity on
human and hamster cell in vitro from Aloe vera gel. Planta Med. 63(1):1821.
Yagi, A., Harada, N., Yamada, H., Iwadare, S., and Nishioka, I. (1982). An- 2185
tibradykinin active material in Aloe saponaria. J Pharm. Sci. 71:11721174.
Yagi, A., Kabash, A., Mizuno, K., Moustafa, S. M., Khalifa, T. I., and Tsuji,
H. (2003). Radical scavenging glycoprotein inhibiting cyclooxygenase 2 and
thromboxane A2 synthase from Aloe vera gel. Planta Med. 69(3):269271.
Yagi, A., Kabash, A., Okamura, N., Haraguchi, H., Moustafa, S. M., and Khal- 2190
ifa, T. I. (2002). Antioxidant, free radical scavenging and anti-inflammatory
effects of aloesin derivatives in Aloe vera. Planta Med. 68(11):957960.
Yagi, A., Machii, K., Nishimura, H., Shida, T., and Nishioka, I. (1985). Effect of
Aloe lectin on deoxyribonucleic acid synthesis in baby hamster kidney cells.
Experientia 41(5):669671.
2195
Yagi, A., Makino, K., Nishioka, I., and Kuchino, Y. (1977). Aloe mannan,
polysaccharide, from Aloe arborescens var. natalensis. Planta Med. 31(1):17
20.
Yagi, A., Nishimura, H., Shida, T., and Nishioka, I. (1986). Structure determination of polysaccharides in Aloe arborescens var. natalensis. Planta Med. 2200
52:213217.
Yamaguchi, I., Mega, N., and Sanada, H. (1993). Components of the gel of Aloe
vera (L.) burm.f. Biosci. Biotech. Bioch. 57(8):13501352.
Yamamoto, M., Ishikawa, M., Masui, T., Nakazawa, H., and Kabasawa, Y.
(1985). Liquid chromatographic determination of barbaloin (aloin) in foods. 2205
J. Assoc. Off. Ana. Chem. 68(3):493494.
Yang, Y., Hou, X. Y., Wang, S. J., Jia, Q. L., Li, Z., and Guo, Z. K. (2004).
Determination of trace zinc, manganese cadmium and lead in aloe by
microwave-digestion atomic absorption spectrometry. Spectrosc. Spect. Anal.
24(12):16721675.
2210
Yaron, A. (1991). Aloe vera: chemical and physical properties and stabilization.
Israel J. Bot. 40:270.
Yaron, A. (1993). Characterisation of Aloe vera gel composition and autodegradation and stabilization of the natural fresh gel. Phytother. Res. 7:S11S13.
December 31, 2009
22
2215
2220
2225
2230
2:5
FSN
BFSN_A_354613
Yaron, A., Cohen, E., and Arad, S. M. (1992). Stabilization of Aloe vera gel
by interaction with sulphated polysaccharides from red microalgae and with
xantha gum. J. Agric. Food Chem. 40(8):13161320.
Yeh, G. Y., Eisenberg, D. M., Kaptchuk, T. J., and Phillips, R. S. (2003).
Systematic review of herbs and dietary supplements for glicemic control in
diabetes. Diabetes Care 26(4):12771294.
Yongchaiyudha, S., Rungpitarangsi, V., Bunyapraphatsara, N., and Chokechaijaroenporn, O. (1996). Antidiabetic activity of Aloe vera L. juice. I Clinical
trial in new cases of diabetes mellitus. Phytomedicine 3(3):214243.
Yoshimoto, R., Kondoh, N., Isawa, M., and Hamuro, J. (1987). Plant lectin,
ATF1011, on the tumor cell surface augments tumor-specific immunity
through activation of cell T specific for the lectin. Cancer Immunol. Immun.:
CII 25(1):2530.
Zahn, M., Trinh, T., Lee-Jeong, M., Wang, D., Abeysinghe, P., Jia, Q., and
Ma, W. (2008). A reversed-phase high-performance liquid chromatography
method for the determination of Aloesin, Aloeresin A and Anthraquinone in
Aloe ferox. Phytochem. Anal. 19:122126.
Zawahry, M. E., Hegazy, M. R., and Helal, M. (1973). Use of aloe

in treating leg ulcers and dermatoses. Int. J. Dermatol. 12(1):68
73.
Zhang, L., and Tizard, I. R. (1996). Activation of a mouse macrophage cell 2235
line by acemannan: the major carbohydrate fraction from Aloe vera gel.
Inmunopharmacology 35(2):119128.
Zhang, X.-F., Wang, H.-M., Song, Y.-L., Nie, L.-H., Wang, L.-F., Liu, B., Shen,
P.-P., and Liu, Y. (2006). Isolation, structure elucidation, antioxidative and
immnumodulatory properties of two novel dihydrocoumarins from Aloe vera. 2240
Bioorg. Med. Chem. Lett. 16:949953.
Zhou, Y., Feng, Y., Wang, H., and Yang, H. (2003). 90-day subchronic
toxicity study of aloe whole-leaf powder. Wei Sheng Yan Jiu 32(6):590
593.
Zonta, F., Bogoni, P., Masotti, P., and Micali G. (1995). High-performance liquid 2245
chromatographic profiles of aloe constituents and determination of aloin in
beverages, with reference to the EEC regulation for flavouring substances. J.
Chromatogr. A 718(1):99106.

Aloe Vera Alimento Funcional 2011

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Aloe Vera Alimento Funcional 2011

Uploaded by

Copyright:

Available Formats

December 31, 2009

Critical Reviews in Food Science and Nutrition, 50:122 (2010)

Aloe vera as a Functional Ingredient

(Reynolds, 1985). This plant is however related to the Liliaceae

Food has drastically changed in the last thirty years. The

December 31, 2009

vera and other species of Aloe are succulent and xerophyte

in particular of polysaccharides. Therefore, different products

The yellow exudate is rich in anthraquinones which are

Figure 1 Structures of Aloin A and B, Aloe-emodin, Aloenin, Aloesin, and

December 31, 2009

ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS

greater quantities of bitter sap and other medicinal components

Most of the authors attribute the beneficial effects of the plant

illnesses. It is essential to understand the chemical composition

December 31, 2009

Chemical composition of Aloe vera gel

Minerals and trace elements

II) NON-NUTRITIVE COMPOUNDS

Atherton (1998); Femenia et al. (1999); Gjerstad

Atherton (1998); Lawless, and Allan (2000)

Atherton (1998); Femenia et al. (1999); Li et al.

galacturonic acid polymers are frequently found (Reynolds and

Atherton (1998); Loots et al. (2007); Ni et al. (2004);

December 31, 2009

ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS

species of Aloe. This disrupts the oligomeric proteins and the

December 31, 2009

et al., 1996). Flavonols such as kaempeferol, quercetin, and

simultaneous determination of metal species, such as Fe (II),

December 31, 2009

ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS

contents in Aloe diminished with the age of the plant (Okamura

eczemas, haemorrhoids, wounds, varicose veins, cracked skin,

December 31, 2009

observed that the complete extract of the leaf is efficient in both

et al., 1998a,b,c; Davis et al., 1989a,c; Heggers et al., 1993) 660

December 31, 2009

ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS

Other Beneficial Effects

BIOLOGICALLY ACTIVE COMPOUNDS

Although some physiological properties of Aloe have been

Contribution of diverse components to the therapeutic action of the

1999; Talmadge et al., 2004). Consequently, the focus is moving

December 31, 2009

December 31, 2009

ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS

been proposed as chemopreventive agents (Kim and Lee, 1997;

nase activity and stimulants of the cellular proliferation, were

December 31, 2009

extract of A. barbadensis Miller gel with a potent antioxidant

the production of macrophages. A study of the ingestion of a

December 31, 2009

ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS

Aloe and sevoflurane (Lee et al., 2004). Luyckx (2002) reported

QUALITY CONTROL AND LEGAL ASPECTS

December 31, 2009

laxative effects (Cobble, 1975). The therapeutic value of Aloe

Investigation of the Authenticity

of the commercial product, as well as to recognize possible

December 31, 2009

ALOE VERA AS A FUNCTIONAL INGREDIENT IN FOODS

very laborious and expensive (Flaster and Lassiter, 2004; Reif

as dietary supplements. This is done to avoid the application