Journal of Ethnopharmacology 216 (2018) 104–119

Contents lists available at ScienceDirect

Journal of Ethnopharmacology
journal homepage: www.elsevier.com/locate/jethpharm

Review

Escalation of liver malfunctioning: A step toward Herbal Awareness T

⁎
Bushra Sultana , Sadaf Yaqoob, Zohaib Zafar, Haq Nawaz Bhatti
Department of Chemistry, University of Agriculture, Faisalabad, Pakistan

A R T I C L E I N F O A B S T R A C T

Chemical compounds studied in this article:
Andrographolide: Pubchem CID:5318517
Lupeol: Pubchem CID: 228079
Stigmasterol: Pubchem CID:5280794
Scopoletin: Pubchem CID: 5280460
Naringenin Pubchem CID: 932
Eudesmane: Pubchem CID:193299
Silymarin: Pubchem CID: 1548994
Silybin: Pubchem CID: 5213
Silychristin: Pubchem CID: 44176
Ellagic acid: Pubchem CID: 4445149
Dulcitol: Pubchem CID: 11850
Mukulol: Pubchem CID:90472510
Quinic Acid: Pubchem CID:6508
Neocrotocembranal: Pubchem CID: 58139347
Phyllanthin: Pubchem CID:358901
Ononitol monohydrate:Pubchem
CID:129711244
Ononitol Chemspider CID:21864849
Parfumine: Pubchem CID: 185623
Bilobanone: Pubchem CID: 5315457
Shikimic acid: Pubchem CID: 8742
Malvidin: Pubchem CID: 159287
Clausenamide: Pubchem CID: 113827
Fargesin: Pubchem CID:10926754
Schizandrin: Pubchem CID:23195
Kutkoside: Pubchem CID: 182265
Kukoamine A: Pubchem CID:4477322
Rhoifolin: Pubchem CID: 5282150
Keywords:
Liver
Disorders
Remedy
Medicinal plants
Bioactive components
Ethnopharmacological relevance: About 2–5% of the world’s population is suffering from liver toxicity including
Pakistan with the second highest rate of hepatitis prevalence. Liver is a vital body organ which not only performs
metabolic activities but also aids in detoxification, storage and digestion of food. Now a day’s malnutrition,
alcohol consumption and drug addiction are major causes of liver diseases throughout the world. In fact, there is
no possible outcome to compensate liver malfunction for long term, and transplantation of liver is the only
option left after the irretrievable injury of hepatic function. Subsequently, natural based therapeutic approaches
are in the process of scrupulous testing as strong hepatoprotective mediator. In this regard plants are well
thought hepatoprotective agents having multiple active components. In this review, based on species’ phar-
macology and safety we have compiled some plants which show strong hepatoprotective activity, main phy-
toconstituents with biological activities and few commercially used herbal formulations.
Materials and methods: Ethnopharmacological information was gathered by an extensive literature survey like
WHO monographs on selected herbal medicinal plants (Vol 1-Vol 4); Principles and Practice of Phytotherapy,
Mills S and Bone K, Churchill Livingstone, London, UK; Herbal Drugs and Phytopharmaceuticals, Wichtl M
Medpharm Press, Stuttgart 3rd edn; Pharmacology and Applications of Chinese Materia Medica Vols 1 and 2,
Chang H-M and But P P-H World Scientific, Singapore; British Herbal Compendium Vol. 2, Bradley P British
Herbal Medicine Association, Bournemouth, UK; ESCOP Monographs 2nd edn. Thieme, Stuttgart, Germany; as
well as by using electronic databases such as Pubchem, Chemspider, http://www.herbal-ahp.org; http://www.
ahpa.org; http://whqlibdoc.who.int/publications/2003/9241546271.pdf; http://www.escop.com, Pubmed,
HubMed and Scopus.
Results: Data for more about 29 plants have been accomplished for their bioactive constituent(s), biological
activities and medicinal uses. Some of the plants have been identified as strong hepato-modulator. Such
knowledge about traditional medicinal plants can be globally applied for safe and evidence based use in
pharmacological applications.
Conclusion: With the rise in liver risks a meek struggle has been made to draw attention toward herbal therapy.
Hepatoprotective constituents of said plants are expressed with chemical structures. However, for certain plants
active constituents are not still isolated/purified but overall plant extract was found effective in providing
protection against hepatic injury. As a future perspective, there is need to purify plant active constituents for
ethnomedical rationale.

1. Introduction species (ROS) is also considered as an imperative contributory factor of

In our body detoxification of various poisonous components is ac-
complished by liver. While detoxifying these compounds, it undergoes
stress leading to malfunctioning of metabolic processes ending in liver
failure and other severe health problems and even death (Marina,
2006). Oxidative stress due to over production of reactive oxygen
many diseases including liver damage. Moreover, liver diseases are also
linked with viral infections (hepatitis A, B, C, D) and other microbial
infections.
Hepatocytes constitute about 70% of all liver cells. Any alteration in
hepatocytes can result into acute and chronic liver dysfunctions.
Hepatocytes play their function at three different levels: (1) they

⁎
Corresponding author.
E-mail addresses: bushrasultana2005@yahoo.com (B. Sultana), sadaf.duggal@yahoo.com (S. Yaqoob), zohaib.zafar36@gmail.com (Z. Zafar), hnbhatti2005@yahoo.com (H.N. Bhatti).

https://doi.org/10.1016/j.jep.2018.01.002
Received 23 May 2017; Received in revised form 3 January 2018; Accepted 3 January 2018
Available online 06 January 2018
0378-8741/ © 2018 Elsevier B.V. All rights reserved.
B. Sultana et al.
prevent necrosis, steatosis and inflammation; (2) stimulate regeneration
process; (3) inhibit fibrosis and cirrhosis. Hepatoprotective/anti-ne-
crotic agents occupy central position because necrosis is a main liver
laceration and if it remains untreated it results into fibrosis.
Consequently, major goal of hepatic therapy is to control necrosis.
Intensive research has been conducted for anti-necrotic agents and it is
established that anti-necrotic agents especially plant flavonoids give a
vital respite to hepatocytes. Flavonoids act by shielding membranes or
by reducing their absorbency to bind with hepatotoxic substances (Gyr
and Meier, 1991).
A significant number of individuals world-wide has been reported
with severe state of hepatopathy induced by drug abuses, alcohol and
other various viral infections (NIH Publication No. 94–1447, NIDDK,
1994). Therefore, protection and treatment of the liver is a major
concern of today’s medical science. Tremendous advancements which
are made in the world of medicine until now, have failed to develop
such a drug that vivify liver activity, inhibit liver degeneration, or sti-
mulate rejuvenation of liver cells (Chattopadhyay, 2003). Moreover,
most of them are immunosuppressive. Consequently, search for in-
novative approaches based on natural sources are under the process of
meticulous testing (Gerbes et al., 2006). In this regard plants are well
thought as strong hepatoprotective mediator having multiple active
components. In the proceeding sections, some valuable information
about hepatoprotective potential of some medicinal plants is given that
will be highly beneficial for readers and pharmaceutical industry as
well.
2. Medicinal plants having hepatoprotective activity
2.1. Acanthaceae
2.1.1. Andrographis paniculata
In traditional systems of medication Andrographis paniculata
(Burm.f.) Nees (Acanthaceae) is well reported for its potential appli-
cation to cure hepatitis. Dried aerial parts of A. paniculata are poten-
tially used for medicinal purposes. Besides its hepatoprotective activity,
this plant has also been traditionally used to cure vaginitis, chicken pox,
burns and eczema owing to antimalarial, antidiarrheal, antivenom and
antipyretic properties (Chang and But, 1986; Leelarasamee, 1990)
(Table 1).
The chief constituent of A. paniculata is ‘andrographolide’ which is a
diterpenoid lactone. The hepatoprotective role of andrographolide is
ascribed to its ability to inhibit hepatic microsomal aniline hydroxylase,
scavenge free radical and prevent lipid peroxidation (Maiti et al.,
2010). Hepa-10 is valuable herbal product of A. paniculata re-
commended by practitioners to hepatic patients (Table 2).
In clinical testing rats with CCl4 induced hepatic injury were orally
treated with water extract of Andrographis paniculata (Burm.f.) Nees at
500 mg/kg p.o. A significant decline in the levels of ALP, SGOT and
SGPT was observed, which might be due to its radical scavenging ac-
tion, inhibition of lipid peroxidation and arresting the activities of he-
patic microsomal enzymes (Nasir et al., 2013).
In an ulcer protective study, rats with pre-induced ulcer were ad-
ministrated with different concentrations of andrographolide (1, 3 and
5 mg/kg) for 30 days. Ulcer sore found to be significantly reduced with
3 mg of andrographolide/kg b.w. The enzyme activities elevated in
response to ulcer were also significantly minimized. This ulcer protec-
tive efficiency of andrographolide might be due to its cytoprotective,
antioxidant and antiacid secretory effects (Saranya et al., 2011)
(Figs. 1–27).
The recommended posology of crude drug is 1–3 g twice daily or
3–9 g as single dose after meal (Table 1). Its uses is inhibited during
pregnancy, mild gastric discomfort and vomiting are reported side ef-
fects of A. paniculata extract hypersensitivity (Table 1)
105
Journal of Ethnopharmacology 216 (2018) 104–119
2.1.2. Hygrophila auriculata
Hygrophila auriculata (Schumach.) Heine (Acanthaceae) is an herbal
plant commonly grown on moist places. Medicinal system makes its use
to treat a number of liver disorders (Vijayakumar et al., 2006). Roots
and seeds have special application in medicines for jaundice and other
hepatic obstruction. This plant is also popular for its anti-diabetes,
antitumor, hypoglycaemic, antibacterial and radical scavenging activ-
ities. Unlike other herbal plants, this plant does not pose side effects or
still no toxicity has been reported using this plant (Table 1). The im-
portant constituents of this plant are flavonoids, terpenoids, lupeol,
butelin and fatty acids (Hussain et al., 2009).
Intake of H. auriculata extract at 100–250 mg/kg b.w for three
weeks lowers TBARS (thiobarbituric acid reactive substances), blood
glucose and hydroperoxide in diabetic rats. This antihyperglycemic
activity might be attributed to the radical scavenging activity of H.
auriculata (Vijayakumar et al., 2006).
2.2. Amaranthaceae
2.2.1. Amaranthus spinosus
Amaranthus spinosus L. (Amaranthaceae) traditionally known as
Chaulai is an annual herb throughout the globe. Medicinally important
part of A. spinosus is its leaves (Table 1). It is used to avert swelling
around stomach and to cure jaundice and other hepatic disorders
(Hema et al., 2006). It is also used as source of antiviral, anti-in-
flammatory, antidiuretic, antimalarial, antimicrobial, and antibacterial
agents (Olajide et al., 2004). A. spinosus encompasses a number of
bioactive components like kaempferol glycosides, quercetin iso-
amaranthine, hydroxycinnamates and amaranthine of antioxidant po-
tential. Stigmasterol is the active ingredient responsible for hepato-
protective function of this plant (Srinivasan et al., 2005; Stintzing et al.,
2004; Hilou et al., 2006). It also contains coumaroyl adenosine,
amaranthoside, stigmasterol glycoside and betaine like trigonelline and
glycinebetaine (Azhar-ul-Haq et al., 2006).
Albino rats with artificially induced oxidative stress and diabetes
(streptozotocin-nicotinamide) were treated with A. spinosus leaf extract
(ASEt) by administrating 250–500 mg/kg bw/day, i.p for twenty-one
days. Biochemical and histological examination show diminution of
blood glucose and ameliorate the enzymatic and non- enzymatic anti-
oxidants. Moreover, administration of leaf extract also minimized the
degenerative changes of pancreatic cells when compared to normal
morphology (Mishra et al., 2012). Not any literature is available con-
cerning A. spinosus extract sensitivity (Table 1).
2.3. Asteraceae
2.3.1. Artemisia gmelinii
Artemisia gmelinii Weber ex Stechm. (Asteraceae) is a perennial sub-
shrubby plant. Aerial part and dried flowering tops has excellent he-
patoprotective effect and used in chronic and acute hepatitis as a strong
remedy (Table 1) (Li et al., 2004; Piao and Quan, 2007). Protective
effects are credited to the presence of number of phytoconstituents like
isofraxidin, esculetin, chlorosacroratin (Zhang, 2006) 2,5-dihydrox-
ycinnamic acid, O-hydroxycinnamic acid, (Zhang, 2002) and scopo-
letin, which is a key component involved in hepatic protection (Fan
et al., 2007). In herbal market, a number of commercial products made
from plants of this family like livomap derived from A. gmelinii are
accessible to patients with liver disorders (Table 2).
In randomized clinical trials alcoholic extract of A. gmelinii with
dosage range of 10, 50 and 100 mg/kg/day shows its strong hepato-
protective effect by reducing oxidative stress in rat plasma
(Mohammadian et al., 2016). Aside from hepatoprotective, extracts of
this plant have also been used to treat patients with loss of appetite and
suffering from gastrointestinal discomfort (Rauchensteiner et al., 2004).
Tea infusion containing 4.5–3.0 g cut flowers are recommended for
healthful effects. Duodenal and gastric ulcer are reported side effects of
 Table 1
Reported Monographs of cited hepatoprotective plants.

Scientific names as Plant part Preparation Active constituents Clinical use Traditional use Folk use Posology Contradiction/ References
B. Sultana et al.

used in medicinal used used Toxicology

plant references

a
Acanthaceae: Dried Aqueous diterpene lactones infectious hepatitis Antibacterial, anti Treatment of colic, 1-3 g crude Gastric discomfort, Chang and Butt, 1986;
b
aerial extract. majorly Common cold, HIV,immunostimulatory,antipyretic, otitis media, drug twice vomiting, should not be Hancke et al., 1995;
c
parts (a) Water- andrographolide, dysentery, urinary antidiarrhoeal,antimalarial,antivenom vaginitis, pelvic daily or 3-9 g used during pregnancy Leelarasamee, 1990;
d
ethanol deoxyandrographolide infections, (b) and atihepatotoxic © inflammatory crude drug as (e) Cáceres et al., 1997;
e
extract (b) (a) disease, single dose Puri et al., 1993
chickenpox, after meal (d)
Andrographis eczema and burns
paniculata (a).
(Burm.f.) Nees
a
Hygrophila Root, seed Ethanol- lupeol, flavonoids, To treat jaundice and Antidiabetic, antitumor and treatment of blood 15-25 ml of No toxicity reported Kanhere et al., 2013;
b
auriculata (a) water (a) terpenoids, butelin (a) liver disorders (b) hypoglycaemic(b) disorders, decoction per Shanmugasundaram
(Schumach.) biliousness, day (a) and Venkataraman,
Heine gonorrhea, 2005
spermatorrhea, and
fever (b)
a
Amaranthaceae: Leaf (a) Methanol stigmasterol, Hepatoprotective and To avert swelling around stomach, to No information No No information available Olajide et al., 2004;
b
Amaranthus spinosus -water extract isoamaranthine, Antidiabetic (d) cure jaundice (d) available information Stintzing et al., 2004;
c
L. (b) quercetin and available Hema et al., 2006;
d
kaempferol glycosides Hilou et al., 2006
(c)
a
Asteraceae: Dried Aqueous Scopoletin, Treatment of hepatitis Aas an emmenagogue, eyewash, Orally for loss of 4.5–3.0 g cut Hypersensitivity,gastric Li et al., 2004;
b
flowering extract (a) Caryophyllene, (b) haemostat, laxative, and to treat appetite, common flowers for as and duodenal ulcer (c) Bradley, 1992a,
tops and baldness, prostatitis and vertigo (b) cold, dyspeptic 1992b;
c

106
aerial part ailments such as Rauchensteiner et al.,
(a) mild 2004
Artemisia gmelinii Chamazulene, spastic discomfort Tea infusions
Weber ex Achillicin, (b) of the (c)
Stechm gastrointestinal
tract, as a choleretic
(b)
a
Cynara cardunculus Dried Water extract Naringenin, Treatment of hepatitis, treatment of anaemia, diabetes, gout, Orally for the 1–2 g of a Hypersensitivity or Mills and Bone, 2000;
b
L. leaves (a) (a) Cynaropicrin, digestive complaints. rheumatism and urinary stones (c). treatment of dried aqueous allergy (e) Kraft, 1997; cEnglisch
cynaroside Adjunct treatment of atherosclerosis and extract (d) et al., 2000;
d
cynarotrioside(b) mild to moderate kidney dysfunctions Holtmann et al.,
hypercholesterolaemia (diuretic) (a). 2003; ePetrowicz et al.,
(b). 1997.
a
Laggera crispata Leaves (a) Methanol- Eudesmane, Antihepatotoxic, anti- anti-inflammatory, antiviral, Antihepatotoxic No No information available Fraga, 2006; bYang
(vahl) Hepper & water (b) sesquiterpenoids, hyperalgesia antibacterial and antileukemia uses(d) effect (d) information et al., 2007; cShi et al.,
J.R.I. Wood quercitin (c) and anti-nociceptive (d) available 2008; dWu et al., 2007;
a
Silybum marianum Dried ripe Water soluble silymarin complex (b) treatment of acute or Treatment of dyspeptic complaints and Treatment of 12–15 g crude Mild laxative effect (c) Feritag et al., 2015;
b
(L.) Gaertn fruits (a) extract (a) chronic hepatitis and gallstones (c). amenorrhoea, drug; Wagner et al., 1974;
c
cirrhosis induced by constipation, 200–400 mg Morazzoni and
diabetes, hay fever, silymarin, Bombardelli, 1995
uterine calculated as
haemorrhages

alcohol, drugs or toxins and varicose veins silybin, in

(a) (a) standardized
preparations
(a)
(continued on next page)
Journal of Ethnopharmacology 216 (2018) 104–119
 Table 1 (continued)

Scientific names as Plant part Preparation Active constituents Clinical use Traditional use Folk use Posology Contradiction/ References
used in medicinal used used Toxicology
B. Sultana et al.

plant references

a
Asclepiadaceae: Root (a) Aqueous ellagic acid, 14- Antihepatotoxic (b) to stimulate the appetite and roots are widely not enough Not yet reported Srivastava et al.,
Decalepis extract aminotetradecanoic used as a health scientific 2006; bSrivastava
hamiltonii (a) acid, 4-(1-hydroxy-1- relieve flatulence, drink, general tonic information to et al., 2007
Wight &Arn. methylethyl)-1-methyl- antiulcer, antidiabetic and stomachic relief determine an
1, 2-cyclohexane diol, 2- (b) (b) appropriate
hydroxymethyl-3- range of doses
methoxybenzaldehyde
(b)
a
Botrychiaceae: Rhizome Methanol- Dulcitol, Ugonins, Antihepatotoxicity and to treat impotency, orally ingested to To relieve sciatica, not enough Nausea, Huang et al., 1994;
b
Helminthostach- (a) water extract flavonoids (c) Anti-inflammatory (b) heal jaundice (b) as laxative, to halt scientific vomiting,dizziness (c) Suja et al., 2004;
c
ys zeylanica (L.) (a) hemorrhage (b) information to Yamauchi et al., 2013
Hook determine an
appropriate
range of doses
a
Burseraceae: Dried Aqueous Mukulol, E- and Z- Treatment of As an expectorant, treatment of Treatment of oleo-gum Minor effects such as Atal et al.,1975;
b
Commiphora oleo-gum extract, guggulsterones, hepatotoxicity, diarrhoea, fatigue, headache, atherosclerosis, resin 3–4.5 g mild diarrhoea, Kotiyal et al., 1980;
c
berryi (Arn.) resin(a) ethanol- guggulsterols-I, -II and hyperlipidaemia and rheumatic in two or restlessness, not Malhotra and Ahuja,
Engl water, -III, cembrene (b) hypercholesterolaemia conditions, cough, three divided recommended during 1971; dVerma and
(c) sore throat doses pregnancy (d) Bordia, 1988; eKotiyal
ethylacetate Jaundice, tropical treatment of burns, as and menopausal (30, 32); et al., 1984
extract (a) an insecticide and insect repellent (d). symptoms. As an petroleum
emmenagogue (e) ether extracts
of the oleo-
gum resin 500

107
mg two or
three times (c)
a
Convolvulaceae: Seed (a) Ethanol- flavonols (a subclass of Hepatoprotective and To recover different circumstances of antioxidant, 6~12 grams High dose may cause Bao et al., 2002;
b
Cuscuta water extract flavonoids), lignans and Antioxidant activity (c) liver and kidney (c) anticancer and (d) insomnia (d) Umehara et al., 2004;
c
chinensis Lam. (a) quinic acid (b) immune Williamson et al.,
stimulatory effects 2005; dYe et al., 2005
(c)
a
Cyperaceae: Rhizome, Ethanol-ether Flavonoids, glycosides, Antidiabetic, anthelmintic, stomachic expectorant, used as refrigerant, No No information available Narayan et al., 2005;
b
Cyperus mindorensis leaves (a) extract (a) triterpenoids (b) hypoglycemic, antidiarrhoeal and diuretic uses (c) demulcent and information Somasundaram et al.,
(Steud.) Huygh hepatoprotectant (c) tonic (c) available 2010; cBharathi et al.,
2011
a
Euphorbiaceae: Stem (a) Aqueous diterpenoids, Hepato-protective Gastrointestinal ulcers, stomach cancers, improves taste, 25 to 50 mg Excess dose causes Pudhom et al., 2007;
b
Croton persimilis extract (a) crotocembraneic acid, activity (b) decreasing chronic liver enlargement useful in dry extract or purgation leading to Kumar et al., 2014;
c
Roxb. neocrotocem-braneic and in remittent fever (b) anorexia,strong 10-20 ml of abdominal cramps and Qadrie et al., 2015
acid, and piercing,bathes decoction (c) dehydration (a)
neocrotocembrana ( b) intestine (b)
a
Euphorbia fusiformis Root, Ethanol- Protopine (alkoloid), As Hepatoprotective to treat hepatotoxicity (b) To treat skin Daily dose of nausea and vomiting (a) Natarajan et al., 2005;
b
Buch.-Ham.ex leaves, water extract adlumidiceine, antimicrobial, anti- diseases, headache, 0.2-0.3 ml of Anusuya and Raju,
D.Don latex (a) (a) copticine, fumariline, inflammatory and diarrhea, joint pain, liquid extract 2010
perfumine (b) antiarthritic agents (b) to reconcile wounds or 120-
and cracks (b) 300 mg of
infusion (a)
a
Phyllanthus amarus Leaves (a) Aqueous, Hypophyllanthin, Hepatoprotective (c) To treat jaundice (c) Liver tonic (c) 4~6 grams of No side effect has been Khatoon et al., 2006;
b
alcoholic- phyllanthin (c) dry leaf reported (d) Naaz et al., 2007;
c
extract (b) powder (d) Prajapati et al., 2015;
d
Asare et al., 2011
(continued on next page)
Journal of Ethnopharmacology 216 (2018) 104–119
 Table 1 (continued)

Scientific names as Plant part Preparation Active constituents Clinical use Traditional use Folk use Posology Contradiction/ References
used in medicinal used used Toxicology
B. Sultana et al.

plant references

a
Fabaceae: Dried Water extract Ononitol monohydrate, Reduce hepatotoxicity Antitumor, antioxidant and anti- Expectorant, 1–2 g of leaf Abdominal pain, Youngken, 1950;
b
Cassia fistula L. leaflets, (a) hydroxyanthracene and occasional inflammatory activity antidysenteric, skin daily at bed Long term use need Leng-Peschlow, 1986;
c
dried ripe glycosides, sennosides constipation (b) disease, dyspepsia, time(a) medical supervision © Bradley, 1992a,
fruit (a) (b) haemorrhoids (b) 1992b
a
Senna occidentalis Dried ripe Methanol sennosides A and B (b) Hepatoprotective Antidote, blood purifier, detoxifying as wound dressing, 1–2 g of fruit Mild abdominal Huang, 1994; bLeng-
(L.) Link fruit(a) extract (a) activity(c). liver an antidysenteric, daily at discomfort © Peschlow, 1986;
c
as carminative bedtime (c). Bradley, 1992b
agent, treatment of
gonorrhoea, (a,b).
a
Senna tora Dried Alcoholic Ononitol, Hepatoprotective (b) Antioxidant, antigenotoxic (b) Cures ulcer (b) 20 mg per kg No adverse effects (c) Dhanasekaran et al.,
leaflets (a) extract (a) anthraquinones, (b) of body 2009; bZhu et al.,
weight (c) 2008; cDhanasekaran
et al., 2009
a
Fumariaceae: Whole Water- Perfumine, Protopine ameliorate bile duct as liver protective agent (b) blood purifier, 3–6 g dry Large dose may cause Gilani et al., 2005;
b
Fumaria indica plant (a) ethanol (alkoloid), blockage and act as diuretic, laxative, powder or diarrhea ( b) Rathi et al., 2008
(Hausskn.) extract (a) adlumidiceine, hepatoprotectant (b) sedative, and decoction
Pugsley copticine, fumariline (b) diaphoretic (b) 50–100 ml in
divided dose
per day (a)
a
Ginkgoaceae: Dried leaf Water- Bilobanone Treatment of hepatitis, None Vermifuge, 120–240 mg Headaches, skin allergy DeFeudis, 1991;
b
Ginkgo biloba L. (a) acetone (b) Shikimic acid mild to moderate treatment of daily in 2 or 3 (c) Squires, 1995;
c
ginkgetin cerebrovascular arthritis, divided doses; Kleijnen and
isoginkgetin insufficiency,Raynaud oedema,chilblains 40 mg extract Knipschild, 1992
ginkgolide M© disease, acrocyanosis(a) (b) is equivalent

108
to 1.4–2.7 g
leaves ©
a
Orobanchaceae: Fruit (a) Alcoholic Kankanoside, acteoside, Hepatoprotective, Anti- treatment of impotence, prevention of Treatment of liver daily dose of No acute or chronic Shimoda et al., 2009;
b
Cistanche extract (a) cistanosides, aging, immune system hepatotoxicity, and gastrointestinal disease, coughs, dried root toxicity (c) Morikawa et al.,
tubulosa echinacosides (c) modulator, antifatigue, disorders such as gastritis and ulcers (b) fever, tuberculosis, 0.5–2 g by 2010; cKamil and Naji,
(Schenk) Wight strong aphrodisiac (b) rheumatism, decoction (c) 2011
ex Hook.f. vomiting of
pregnancy,
hypothermia,
dyspnoea, and
nervous disorders
(d)
a
Primulaceae: Stem (a) Methanol quinones, flavonoids, To reduce inflammation anti-inflammatory, anti-rheumatic, anti- To heal ulcers and No No information available Xu et al., 2004;
b
Aegiceras -water (a) lignans, phenolic acids, of liver (c) diabetic, and anti-asthmatic uses (c) other hepato information Zhang et al., 2005;
c
corniculatum saponins, sterols, injuries © available Wang et al., 2006
(L.) Blanco tannins and triterpenes
(b)
a
Rosaceae: Fuit juice, Aqueous Malvidin, Hepatoprotective (a) Chronic inflammation, peptic ulcer, treat 5–10 ml of No reported toxicity (c) Han et al., 2005; cLala
extract (a) proanthocyanidine (b) liver failure (b) fruit juice et al., 2006;
c
Aronia melanocarpa Dry colorectal cancer (a) daily (c) Wu et al., 2006
berries (a)
a
Rutaceae: Clausena Leaves Methanol- Clausenamide and Hepatoprotective (c) Treat coughs, asthma, hepatitis and Gastrointestinal 3–10 g crude Mild skin allergy (b) Fletcher, 2001;
b
lansium (Lour.) and seeds water extract clausenacoumarine (b) dermatological diseases (c) ailments such as dry extract Adebajo et al., 2009;
c
Skeels (a) (a) ulcers and chronic daily (b) Zhao et al., 2004
inflammation (c)
(continued on next page)
Journal of Ethnopharmacology 216 (2018) 104–119
 Table 1 (continued)

Scientific names as Plant part Preparation Active constituents Clinical use Traditional use Folk use Posology Contradiction/ References
used in medicinal used used Toxicology
B. Sultana et al.

plant references

a
Zanthoxylum Bark (a) Ethanol- fargesin, asarinin, Hepatoprotective (b) antifungal, anthelmintic and toothache, colic, No No information available Tiwary et al., 2007;
b
armatum DC. water (a) armatamid, antibacterial properties (b) and rheumatism (b) information Ranawat et al., 2010
xanthoplanine, available
dictamine and berberine
(b)
a
Schisandraceae: dried ripe Water soluble schizandrin, treatment of psychosis, As an astringent, antitussive, Treatment of Average daily Minor effects like Cheng et al., 2013;
b
Schisandra fruits (a) deoxyschizandrin, gastritis, hepatitis and antidiarrhoeal, expectorant and sedative chronic cough and dose: heartburn, Wang et al., 2000;
c
chinensis gomisin N, gomisin A fatigue (d) (d) asthma, diabetes, 1.5–6.0 g of Hancke et al., 1999
and urinary tract the dried
Water- ( ± )–schizandrin(c) disorders (d) fruits (d) stomach pain, skin
ethanol (b) allergy (c)
a
Scrophulariaceae: dried Aqueous Kutkoside, iridoid Hepatoprotective To treat anaemia, asthma, obesity, To treat fever, 1–3 g of the No information was Girish et al., 2009;
b
rhizome extract, glycosides, cucurbitacin activity © malaria, stomach ache, as an anti- immune disorders, powdered found Yadav and
with root alcoholic inflammatory agent, a cathartic, a skin diseases, crude drug (c) Khandelwal, 2008;
c
Picrorhiza kurroa (a) extract (a) triterpenes, apocynin, cholagogue and as emmenagogue (d) bronchial asthma, Tiwari et al., 2012;
(b) viral hepatitis (d) Saleh, 2007; dHussain
et al., 2009
a
Solanaceae: Fruit (a) Aqueous Kukoamine, zeaxanthin, Hepatoprotective (b) Liver tonic (b) Antioxidant (b) Not reported No information available Ahna et al., 2014; bHa
Lycium chinese extract (a) zeaxanthin dipalmitate et al., 2005
(a)
a
Urticaceae: Roots (a) Methanol- Rhoifolin. stearic acid, Hepatoprotective, As fiber source (c) As diuretic, No No information available Sancheti et al., 2011;
b
Boehmeria nivea water (a) boehnic acid, β- hyperlipidemia, antipyretic and liver information Huang et al., 2006;
c
(L.) Guadich sitosterol (b) hyperglycemia agent (c) protective agent (c) available Coon and Ernst, 2004

109
9
8
7
6
4
3
2
1

21
20
19
18
17
16
15
14
13
12
11
10
2011).

Sr #
Table 2

Livol
Livin
Livex

Adliv

Hepex

Vimlin
Livarin
Livodin

Acilvan
Hefiaye

Legalon
Triguliv

Ginseng
Hepa-10
Livomap

Livatona
Amlycure

Livomycin
Hepatomed
formulation

Jaundex syrup
Marketed Herbal

2.3.2. Cynara cardunculus

Fig. 2. Lupeol.

A. gmelinii extract hypersensitivity (Table 1).

Cassia fistula L.

Fig. 1. Andrographolide.
Ginkgo biloba L.
Acorus calamus L.

Boerhavia diffusa L.
Justicia adhatoda L.

Cassytha filiformis L.
Glycyrrhiza glabra L.
Aloe vera (L.) Bum.f.
Achillea millefoiliven L.

and Solanum nigrum L.

Artemisia absinthium L.

Senna alexandrina Mill.

Zingiber officinalis Roscoe

Senna occidentalis (L.) Link
Plant used in formulation

Silybum marianum (L.) Gaertn.

Calotropis gigantea (L.) Dryand.

Picrorhiza Kurroa Royle ex benth.

Andrographis paniculate (Burm.f.) Nees

Phyllanthus amarus Schumach. &Thonn.

Aconitum heterophyllum Wall. ex. Royle

Cichorium intybus L., Eclipta prostrata (L.) L.

perennial thistle. This plant is common in Southern Europe where it is

Cynara cardunculus L. (Asteraceae) generally known as Artichoke is
Herbal formulations commercially being used in liver complications (Suralkar et al.,
Journal of Ethnopharmacology 216 (2018) 104–119
B. Sultana et al. Journal of Ethnopharmacology 216 (2018) 104–119

Fig. 8. Silybin.
Fig. 3. Stigmasterol.

Fig. 4. Scopoletin.

Fig. 9. Silychristin.

Fig. 5. Naringenin.

Fig. 10. Ellagic acid.

Fig. 6. Eudesmane.

Fig. 11. Dulcitol.

Fig. 7. Silymarin.

consumed as vegetable and also formulated in herbal tea. However,

younger leaf and tender artichokes are preferable for consumption. Due
to its great nutritive values that aids in digestion, this plant also
strengthens the liver and gall bladder functions (Shen et al., 2010). The Fig. 12. Mukulol.
key components of artichoke elixir are naringenin, apigenin glycosides
and luteolin-7-glucoside. Naringenin primarily exerts antihepatotoxic
effect (Fratianni et al., 2007).

110
B. Sultana et al. Journal of Ethnopharmacology 216 (2018) 104–119

Fig. 17. Ononitol.

Fig. 13. Quinic Acid.

Fig. 18. Parfumine.

Fig. 14. Neocrotocembranal.

Fig. 19. Bilobanone.

Fig. 15. Phyllanthin.

Fig. 20. Shikimic acid.

Fig. 16. Ononitol monohydrate (6-methoxycyclohexane-1.2.3.4.5-pentaol hydrate).

Clinically extract of C. cardunculus was found effective remedy to

treat hepatitis. Traditionally diabetes, rheumatism and urinary stones
has also been treated using C. cardunculus extracts (Table 1). In a trial
Fig. 21. Malvidin.
leaf extract of C. cardunculus at 0.25 g/kg in albino rats increased the

111
B. Sultana et al.
Fig. 22. Clausenamide.
Fig. 23. Fargesin.
Fig. 24. Schizandrin A.
Fig. 25. Kutkoside.
112
Journal of Ethnopharmacology 216 (2018) 104–119
H
O
H
O
O
O
O H
O
H
O O O
H
O
O
H
O O
H
O
H
Fig. 27. Rhoifolin.
levels of biochemical markers. Antioxidant components in the extract
are responsible for therapeutic potential of C. cardunculus L. against
paracetamol hepatic damage in albino rats (Diab et al., 2013). Hy-
persensitivity has also been reported by using high doses of the extract
(Petrowicz et al., 1997) Usually 1–2 g of a dried aqueous extract has
been found effective range of crude drug (Table 1).
2.3.3. Laggera crispata
Laggera crispata (vahl) Hepper & J.R.I. Wood (Asteraceae) histori-
cally being applied to cure hepatic ailments. Various parts of this plant
have anti-inflammatory, antiviral, antibacterial and antileukemia
properties with no side effects or reported toxicity (Wu et al., 2007)
(Table 1). Bioactive components like eudesmane (responsible for he-
patoprotective effect), pterodondiol, ilicic acid, artemitin and chrysos-
plenetin have been found in the ethanolic extract of L. pterodonta (Shi
et al., 2008).
Ethnomedical rationale of L. pterodonta methanolic leaf extract at
200–400 mg/kg revealed not only its anti-hyperalgesia effect but also
showed anti-nociceptive chattels attributed to existence of tannins, sa-
ponins and carbohydrates. The extract dose of 400 mg/kg exhibited a
significant analgesic activity of about 19.75% (Olurishe and Fatima,
2014).
2.3.4. Silybum marianum
Silybum marianum (L.) Gaertn. (Asteraceae) is an important medic-
inal plant. The hepato-protective constituent of S. marianum is sily-
marin which is obtained from its fruit. Silymarin complex is a rich
mixture of silychristin, silybin, and silymarim (Freitag et al., 2015).
Silybin is highly effective in targeting the membranes of liver cells re-
sulting into regeneration of cells (Rambaldi et al., 2007; Greenlee et al.,
2007). In hepatoprotectivity silymarin primarily performs four levels of
action: 1) scavenges free radicals (antioxidant activity); 2) regulates the
Fig. 26. Kukoamine A.
B. Sultana et al.
membrane permeability, provides membrane protection against drug
injury; 3) stimulates DNA polymerase-I, regulate DNA transcription
which increases the synthesis of ribosomal RNA; 4) important role in
regeneration of liver cells and protein synthesis (Vargas-Mendoza et al.,
2014). The active constituents of this plant have also been reported to
break down gall stones. This plant is also important for diabetes, hay
fever, constipation and amenorrhoea (Table 1).
In a number of randomized studies conducted on alcohol-induced
hepatic patients, 420 mg/day of silymarin was found to be very effec-
tive in restoration of liver functions. The silymarin efficacy is mainly
attributed to inhibit the fibrotic activity. Silymarin is being marketed as
capsule formulations of 200 mg concentrated extract of S. marianum,
each capsule contains 140 mg of silymarin (Saleh, 2007). Legalon is
commercially available product of S. marianum being used in liver ail-
ments. Mild laxative effects have been reported in patients with sily-
marim sensitivity (Table 1).
2.4. Asclepiadaceae
2.4.1. Decalepis hamiltonii
Decalepis hamiltonii Wight & Arn. (Asclepiadaceae) is a climber bush.
Cylindrical fleshy roots are used as pickles and culinary spice. The roots
are also of major concern due its manifold health attributes. Roots have
therapeutic potential to fix liver disorders as well as stomach ache
(Srivastava and Shivanandappa, 2010). These also possess anti-in-
flammatory, antipyretic, antifungal activities. These act as potent ap-
petizers and blood purifier. Most of the medicinal benefits are mainly
associated with antioxidant properties of root extract (Srivastava et al.,
2007). Some major antioxidants are 2-hydroxymethyl-3-methox-
ybenzaldehyde, 14-aminotetradecanoic acid, 4-hydroxyisophthalic
acid, ellagic acid, 4-(1-hydroxy-1-methylethyl)-1-methyl-1,2,4,8 trihy-
droxybicyclo [3.2.1] octan-3-one and 2-cyclohexane diol (Srivastava
et al., 2006).
Rats with ethanol induced hepathopathy were treated with aqueous
extract of roots of D. hamiltonii Wight & Arn. at 50, 100, 200 mg/kg b.w
for seven days. Significant inhibition of ethanol induced oxidative stress
occurred by root extract due to suppression of protein carbonylation
and lipid peroxidation without causing any toxicity in the subject
(Srivastava and Shivanandappa, 2010).
2.5. Botrychiaceae
2.5.1. Helminthostachys zeylanica
Helminthostachys zeylanica (L.) Hook (Botrychiaceae) is an herbac-
eous medicinal plant. It possesses aphrodisiac, antiviral and hepato-
protective properties and used for the treatment of various hepatic
disorder. Plant rhizome comprises of different phenolics like dulcitol,
ugonin (A, B, C, D) fucosterol and stigmasterol (Au et al., 2011). The
plant extract exhibits pain relieving properties, helpful in sciatica, acts
as moderate laxative, and has been used to halt hemorrhage. Rhizome
elixir traditionally being used to treat impotency, administrated orally
to heal jaundice. Leaf juice mitigate tongue blisters (Bhawna and
Kumar, 2009) but vomiting and nausea have been reported under over
dose (Table 1).
2.6. Burseraceae
2.6.1. Commiphora berryi
Commiphora berryi (Arn.) Engl. (Burseraceae) is a small tree like
spiny shrub well distributed throughout the Asia. This plant has potent
hepatoprotective effects (Gowrishankar et al., 2004b). The biological
attributes of this plant include antibacterial, anti-inflammatory, anti-
oxidant and antiulcer activities (Gowrishankar et al., 2004a). The chief
phytoconstituents of C. berryi ethanolic extract are phytosteroids, gums,
proteins, tannins and phenolics. Mukulol is key component which fights
against jaundice and also potent in the treatment of
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Journal of Ethnopharmacology 216 (2018) 104–119
hypercholesteralaemia. Certain studies also reveal that the plant extract
has also been used as an emmenagogue (Kotiyal et al., 1984) (Table 1).
Regular oral intake of C. berryi methanolic extract at the dosage rate
of 100 and 200 mg/kg bw for 15 days produce significant hepatopro-
tective function by reducing the serum enzymes of liver (Shankar et al.,
2008). As its continuous usage causes restlessness and mild diarrhea, it
is avoided during pregnancy (Verma and Bordia, 1988) (Table 1).
2.7. Convolvulaceae
2.7.1. Cuscuta chinensis
Cuscuta chinensis Lam.(Convolvulaceae) is commonly used Chinese
herb recommended widely for kidney disorders. Seed of this plant has
high content of flavonoids and has long been used traditionally in Asian
countries to recover different poor conditions of liver and kidney (Bao
et al., 2002). C chinensis exhibits antioxidant, anticancer and immune
stimulatory effects (Umehara et al., 2004). Pharmacologically active
components of C chinensis are flavonols (a subclass of flavonoids), lig-
nans and quinic acid (Williamson et al., 2005; Ye et al., 2005) that have
been identified in ethanolic extract not in aqueous extracts.
Nanoparticle system is now being practiced for poorly soluble
herbal medicine and to reduce treatment dosage. Due to poor solubility
of active constituents of C. chinensis a nanosuspension of C. chinensis
Lam. was prepared and compared in activity and dosage range with
methanolic extract of C. chinensis Lam. Nanosuspension at 25 and
50 mg/kg gave better antioxidant and hepatoprotective function as
compared to dose of methanolic extract (125 and 250 mg/kg) which is
five times higher than amount of nanosuspension (Yen et al., 2008). Its
reduce dosage is mandatory as its heavy dose lead to insomnia (Ye
et al., 2005) (Table 1).
2.8. Cyperaceae
2.8.1. Cyperus mindorensis
Cyperus mindorensis (Steud.) Huygh (Cyperaceae) commonly known
as white water sedge is a perennial herb distributed all over the world.
Ethnomedical studies showed that this plant possesses anthelmintic,
stomachic expectorant, antidiarrhoeal and diuretic activities (Narayan
et al., 2005). Tumors, diabetes, fever and splenopathy can also be
treated using C. mindorensis. Rhizome of this plant possesses glycosides,
phenols, flavonoids, lipids, saponins and terpenes (Raju et al., 2008).
Antioxidant components present in C. mindorensis extract might be the
cause of its hepatoprotective effect.
Ethnomedicine reviewed the use of ethanolic and ethereal extract of
Cyperus mindorensis rhizome. Both extracts at 100–200 mg/kg, p.o. for 7
days showed significant hepatoprotection compared to control
(Silymarin). Histopathological studies also revealed liver protection
from injury (Somasundaram et al., 2010). In literature, no contradiction
has been found on the usage of this plant (Table 1).
2.9. Euphorbiaceae
2.9.1. Croton persimilis
Croton persimilis mull. Arg. (Euphorbiaceae) is medium-sized tree
found mostly in dry places. Medicinal properties of C. persimilis are
tremendous ranging from treating various gastrointestinal ulcers, sto-
mach cancers, in remittent fever to cure chronic liver enlargement
(Kumar et al., 2014). Aerial parts show hypotensive activity and in
chronic hepatitis paste of aerial parts applied externally to the hepatic
region. Active constituents are diterpenoids, crotocembraneic acid,
neocrotocem-braneic acid, and neocrotocembranal (Qadrie et al.,
2015). But in some cases, its high doses led to dehydration and ab-
dominal cramps (Pudhom et al., 2007) (Table 1).
2.9.2. Euphorbia fusiformis
Euphorbia fusiformis Buch.-Ham.ex D.Don (Euphorbiaceae) is a
B. Sultana et al.
perennial herb, grows wildly in tropic regions of the world.
Traditionally tuberous roots of the plant are being used to treat hepa-
totoxicity (Anusuya and Raju, 2010). Superficial application of plant’s
sap heals skin diseases, reconcile wounds and cracks. To relieve head-
ache crushed leaf paste is applied on forehead. Although dried powder
of rhizome is orally given to treat diarrhea and joint pain but nausea
and vomiting have been reported as toxicity under same circumstances
(Natarajan et al., 2005) (Table 1). Extensive pharmacological research
has showed that E. fusiformis possess antimicrobial, anti-inflammatory
and antiarthritic properties (Natarajan et al., 2005).
The ethanol extract of E. fusiformis Buch.-Ham.ex D.Don tuber at
250 mg/kg p.o. show amazing hepatoprotectivtiy against rifampicin
(wistar albino rats; model animal). The histological profile of rat liver
attests safer use of ethanol extract even at higher dose (LD (50)
10,000 mg/kg bw) (Anusuya and Raju, 2010). The hepatoprotective
effect is due to a combination of different mechanisms of antioxidant
compounds.
2.9.3. Phyllanthus amarus
Plants of family Euphorbiaceae have wide medicinal importance.
Phyllanthus amarus Schumach & Thonn. (Euphorbiaceae) traditionally
being used by practitioners for the treatment of jaundice. It has been
found that aqueous extract of its leaves performs hepatoprotective
functions by acting at two levels: 1) block the reaction between the
antibody and antigen of hepatitis B virus; 2) inhibit endogenous DNA
polymerase of HBV which is necessary for HBV replication. (Khatoon
et al., 2006). The chief constituents of P. amarus are hypophyllanthin
and phyllanthin that exhibit antihepatotoxicity against D-galactosa-
mine and carbon tetrachloride induced toxicity (Naaz et al., 2007). In
the market of herbal medicine hepex is the herbal product of P. amarus
being used by hepatic patients (Table 2).
Oral intake of aqueous and alcoholic P. amarus extracts exhibit
chemoprotective effect against azaserine induced pancreatic cancer in
Wistar rats (Prajapati et al., 2015). In another test toxicity of P. amarus
plant extract was determined on female Sprague-Dawley rats. Two
groups of rats weighing (150–200 g) were treated with oral gavage of
aqueous leaf extract ranging from 2000 to 5000 mg/kg b.w. within
24 h. A third group of rats was treated with drinking water only. Bio-
chemical and hematological examinations of various body organs did
not show any abnormality. Among the experimental groups results did
not differ significantly and LD50 for aqueous extract is less than
5000 mg/kg per body weight (Asare et al., 2011). 4–6 g of dried leaf
powder promotes healthy effect on liver with no reported toxicity
(Table 1)
2.10. Fabaceae
2.10.1. Cassia fistula
Cassia fistula L. (Fabaceae) commonly known as golden shower. All
parts of the plant especially dried leaves and ripe fruit have medicinal
importance in hepatic disorders (Table 1). C. fistula possess numerous
biological activities including aperient, laxative, astringent, and pur-
gative. The plant also has antioxidant, anti-inflammatory, antitumor
and hepatoprotective activities (Manonmani et al., 2005). Therefore,
plant has been found to be effective in the treatment of several dis-
orders like treatment of abdominal, stomach, liver, and throat tumors.
It is also used for burns, constipation, diarrhea, epilepsy, pimples,
malaria, and liver ailments. Bioactive components are free and glyco-
side flavonoids (kaempferol, anthroquinone, bianthroquinone glyco-
side) (Dawada et al., 2012). Ononitol monohydrate is the active con-
stituent responsible for hepato-activity. Famous herbal product derived
from C. fistula is livarin (Table 2).
Alcoholic root extract of C. fistula was investigated against acute and
massive state of hepatopathy in male albino rats. The extract possess
dose dependent (200 mg/kg and 100 mg/kg/b.w) protective function.
All the marker enzymes were significantly decreased. The dose of
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Journal of Ethnopharmacology 216 (2018) 104–119
200 mg/kg was found to be quite promising and gave comparable re-
sults with a standard drug, Silymarin (Dawada et al., 2012). 1–2 g of
dry leaf powder daily at bed time is the effective intake form of C.
fistula. Mild abdominal pain is a possible side effect of C. fistula and its
long term use need medical supervision (Table 1).
2.10.2. Senna occidentalis
Senna occidentalis (L.) Link (Fabaceae), is a communal wild plant. Its
dried ripe fruit is used in a variety of herbal formulations (Mohammed
et al., 2012) (Table 1). The plant has anti-inflammatory, anti-malarial,
analgesic, antipyretic activities. Unani practitioners use this plant for
multipurpose therapy such as an antidote, expectorant, blood purifier,
anti-inflammatory agent and in liver treatment (Sheebarani et al.,
2010). It is mainly used as liver detoxifier to strengthens the liver.
Bioactive constituents are mainly sennosides A and B, anthraquinones,
flavaaonoids, phytosterol and polysaccharides (Sadiq et al., 2012).
Oral intake of methanolic fraction of S. occidentalis at 200 mg/kg bw
help in the restoration of serum enzymatic levels of albino rats having
paracetamol induced hepatotoxicity. Histopathological test and nor-
malization of Vit-C, Vit-E, SOD, GSH levels further confirmed the he-
patoprotective function of S. occidentalis methanolic extract (Rani et al.,
2010). Hepatic drug derived from S. occidentalis is aclivan (Table. 2).
1–2 g of dry fruit taken at bed time is usually found effective for
medication. Mild abdominal discomfort are its reported adverse effects
(Table 1).
2.10.3. Senna tora
Senna tora (L.) Roxb. (Fabaceae) is a shrub widely practiced for
curing ulcers. S. tora leaves have been found to be very useful in healing
liver disorders (Table 1). This plant show antioxidant and anti-
genotoxicity. Hepatoprotective agent isolated from this plant is ono-
nitol (a class of glycoside) (Dhanasekaran et al., 2009). Other beneficial
components are anthraquinones (Zhu et al., 2008).
Ononitol separated from the leaves of S. tora was given to male rats
at the rate of 20 mg/kg bw for about eight days. Silymarin taken as
reference drug administrated at the same rate (20 mg/kg bw for 8
days). Experimental results reflect that ononitol is more potent hepa-
toprotectant compared with silymarin. Histopathological tests revealed
ononitol with no adverse side effect (Dhanasekaran et al., 2009).
2.11. Fumariaceae
2.11.1. Fumaria indica
Fumaria indica (Hausskn.) Pugsley (Fumariaceae) known as ‘‘par-
pata’’ is a small annual herb widely grow in plains and lower hills. It has
long been used as liver protective agent. It also possesses various other
medicinal attributes like, blood purifier, diuretic, laxative, sedative, and
diaphoretic (Gerbes et al., 2006). Protopine (alkoloid), adlumidiceine,
copticine, fumariline, perfumine are regarded as active component
(Rathi et al., 2008).
F. indica water-ethanol extract (50%) was compared with butanol,
hexane and chloroform fractions. Among fractions maximum hepato-
protection (90%) was achieved with butanol fraction. Because in bu-
tanol fraction active constituent alkaloid protopine was highly quanti-
fied (0.2 mg/g). The protopine in concentration range upto 10–20 mg
p.o. shows proportionate effect to silymarine (reference drug) at 25 mg
p.o. (Rathi et al., 2008) Over dose may caused diarrhea (Rathi et al.,
2008) (Table 1).
2.12. Ginkgoaceae
2.12.1. Ginkgo biloba
Ginkgo biloba L. (Ginkgoaceae) leaves are considered as one of the
most used herbal medication. Although leaves and seeds both have
medicinal value however, seed ingestion poisoning has been reported.
Currently research is being focused on the medical applications of its
B. Sultana et al.
green leaves. Ginkgo widely used to cure dementia (DeKosky et al.,
2008). This plant has cardioprotective, antiasthmatic, antoxidant, an-
tidiabetic and hepatoprotective activities (Shenoy et al., 2002; Naik and
Panda, 2008). Moreover, it also has nootropic properties therefore used
as memory enhancer (Mahadevan and Park, 2008). Active components
are flavonol glycosides (quercetin, kaempferol, and isorhamnetin),
shikimic acid, bilobanone and ginkgolides. Oral intake of G. biloba
phytosomes at 25 mg/kg & 50 mg/kg, i.p. for seven days produce re-
markable hepatoprotection proportionate to silymarin (200 mg/kg,
p.o.) (Naik and Panda, 2008). Ginseng is widely used drug derived from
Ginkgo biloba (Table 2). In certain cases, it caused skin allergy (Kleijnen
and Knipschild, 1992) (Table 1).
2.13. Orobanchaceae
2.13.1. Cistanche tubulosa
Cistanche tubulosa (Schenk) Wight ex Hook.f. (Orobanchaceae) is a
perennial plant mostly found in Arabia, Asia and North Africa. Due to
lacking in chlorophyll this plant grows on the roots of Calotropis species
to get nutrients. Use of ripe fruit is effective in hepatitis, constipation,
infertility and body weakness (Table 1). Several bioactive components
like, phenylethanoids iridoids and kankanosides are main hepatoactive
constituents isolated from C. tubulosa (Morikawa et al., 2010).
The kidney tonifying potential of 70% alcoholic extract of C. tubu-
losa was clinically tested for hepatoprotective function. According to
clinical trial the single oral dose of extract at 4470, 4869, 5308 and
6400 mg/kg, p.o. did not produce any hostile effect in mice. The tested
dose of plant extract did not produce any abnormal sign of salvation,
constipation, nasal liberation, diarrhea, lacrimation, tremors, or death
during the observation time. The LD 50 was implicit to be > 6.4 g/kg
(Kamil et al., 2011).
2.14. Primulaceae
2.14.1. Aegiceras corniculatum
Aegiceras corniculatum (L.) Blanco (Primulaceace) is commonly used
in the handling of ulcers and other hepato injuries (Xu et al., 2004).
Stems extract possess anti-inflammatory, anti-rheumatic, anti-diabetic,
and anti-asthmatic activities (Gurudeeban et al., 2012). Bioactive
components responsible for above mentioned activities are mainly poly
phenols including quinones, triterpenes, lignans, tannins, phenolic
acids, sterols, saponins and flavonoids (Zhang et al., 2005; Wang et al.,
2006). Hepatoprotective and anti-inflammatory actions of its stem ex-
tracts are correlated with the antioxidants present in it (Roome et al.,
2008). The hepatoprotective effect is due to a combination of different
mechanisms of antioxidant compounds.
In an in vivo (rat paw edema) and in vitro study (human platelets)
highly polar methanolic extract (100 mg/kg) of A. corniculatum (L.)
Blanco. exhibited strong anti-inflammatory potential by stimulating
multiple mechanisms. Like the reduction of carrageenan-induced cell
intrusion in rat and increased release of histamine and serotonin au-
thenticate its traditional use against inflammation (Roome et al., 2008).
No information till now is available regarding effective posology
and adverse reactions of A. corniculatum extract (Table 1).
2.15. Rosaceae
2.15.1. Aronia melanocarpa
Aronia melanocarpa (Michx.) Elliott (Rosaceae) is a woody shrub. It
is also known as black chokeberry. Chokeberries are effective in chronic
inflammation (Han et al., 2005), colorectal cancer (Lala et al., 2006),
peptic ulcer and liver failure (Valcheva-Kuzmanova et al., 2004). Phy-
tochemicals responsible for medicinal activities are considered as
polyphenols. The fruits are rich in polyphenols especially anthocyanin
(flavonoids). Total anthocyanin and proanthocyanidine contents in
chokeberries are 1480 and 664 mg per 100 g of fresh fruit (Wu et al.,
115
Journal of Ethnopharmacology 216 (2018) 104–119
2004, 2006). Malvidin is an important anthocyanin responsible for its
bioactivity.
Oral intake of A. melanocarpa fruit juice (5, 10 and 20 ml kg−1) for
four days to rats suspected with acute CCl4 liver damage shows dose
dependent reduction in necrotic changes. Fruit juice increase the level
of GSH content in liver as well as control the levitation of MDA for-
mation (Valcheva-Kuzmanova et al., 2004). Daily intake of 5–10 ml of
fruit juice is effective remedy for liver malfunctioning (Table 1).
2.16. Rutaceae
2.16.1. Clausena lansium
Clausena lansium (Lour.) Skeels (Rutaceae) commonly known as
Wampee, is a scented attractive shrub/small tree (3–8 m tall) having
quite grapelike fruits that are comparatively similar to citrus fruits. It is
generally grown in China, Indonesia, Malaysia, Vietnam and
Philippines. This plant has a number of medical applications. Leaves
and seeds are used for gastro-intestinal diseases. Moreover, leaves have
also been used for curing asthma. The immature fruit, stem and dried
roots are being used for the treatment of malaria and respiratory dis-
orders and (Zhao et al., 2004). Its topical use is avoided as it caused
mild skin allergy (Adebajo et al., 2009).
Beside multiple medical consequences; this plant is also used in the
healing of severe kind of hepatitis. Hepatoprotective attributes relate to
the presence of amides and coumarins like clausenacoumarine, clau-
senamide which are extracted from the leaf (Adebajo et al., 2007).
Methanolic extract of C. lansium show substantial outcome against
hepatotoxicity and diabetes. After 30 min of administration methanolic
extract at 100 mg/kg persuaded anti-hyperglycaemic activity of about
15.8%. In commensurate to control insulin level of plasma was in-
creased up to 38.5% after 60 min of extract intake. Its antidiabetic
activity is attributed by stimulating the release of insulin.
Administration of 100–200 mg/kg i.p. of methanolic extract diminished
hepatotoxicity by reducing phenobarbitone-sleeping time (5.3–8.4%),
by reversing serum liver proteins (7.0–8.8%) and by preventing the
increase of ALP, ALT and AST activities of plasma (13.2–83.8%). This
potential of C. lansium validate its pharmacon for hepatitis, bronchitis
and gastro-intestinal inflammation (Adebajo et al., 2009). 3–5 g of
crude dry extract is recommended dose range. Mild skin allergy has
been reported if C. lansium intake exceeds the limit (Table 1).
2.16.2. Zanthoxylum armatum
Zanthoxylum armatum DC. (Rutaceae) is being used in Ayurvedic for
many years. It is sub-deciduous shrub having anthelmintic, stomachic
and carminative properties. Besides this, extracts of this plant have
displayed prominent antifungal, anthelmintic and antibacterial prop-
erties (Tiwary et al., 2007). Active components having phytopharma-
ceutical importance are amyrins, fargesin, dictamine and berberine
(Naveen et al., 2005). Intake of ethanolic bark extracts (100, 200,
400 mg/kg) for seven days enhanced the level of glutathione, catalase
and superoxide dismutase (antioxidants) which reduced the level of
AST, ALT, ALP and serum enzymes (causing hepatotoxicity) and led to
the recovery of damaged cells in Wistar rats. (Ranawat et al., 2010). Not
any kind of adverse effect has yet been reported regarding its usage.
2.17. Schisandraceae
2.17.1. Schisandra chinensis
Schisandra chinensis (Turcz.) Baill. (Schisandraceae) is very effective
medicinal plant commonly used in liver ailments. The whole plant is
valuable but dry berries are used for curing liver intoxication. Dry
berries not only provide hepatic protection but also aids in revival of
normal hepatic functions. Traditional and folk uses of this plant are for
the treatment of asthma, as an astringent, antitussive, antidiarrhoeal,
expectorant and sedative effects (Table 1). Bioactive components of this
plants are schizandrins (A, B, C, D and γ) (Chen et al., 2013).
B. Sultana et al.
Water and alcoholic extract of S. chinensis have significant effect on
the rat liver microsomal enzymes. In an in vivo and in vitro study, it
was found that multiple dosing of water (100–500 µg × ml−1) and
alcoholic (28–120 µg x ml−1) extracts for about seven days exhibited
significant inhibition of microsomal enzymes. The possibility of inter-
action depends on amount of extract and subtype of microsomal en-
zyme (Wang et al., 2000).
The effective dose of daily intake ranges from 1.5 to 6.0 g of the
dried fruits. Minor side effects like heartburn, stomach pain and skin
allergy have been reported (Table 1).
2.18. Scrophulariaceae
2.18.1. Picrorhiza kurroa
Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae) is one of the
oldest medicinal plants. Rhizome extract of P. kurroa showed strong
protection against hepatic damage (Girish et al., 2009). The elixir of P.
kurroa rhizome contains powerful anti-inflammatory agents like apoc-
ynin, picroside I, kutkoside, cucurbitacins, iridoid glycosides, picroside
II, and iridoid glycosides, which reduce platelet aggregation. A mixture
of kutkoside and picroside I also known as ‘picroliv’ possesses strong
hepatoprotective activity against galactosamine, paracetamol, aflatoxin
and thioacetamide induced hepatotoxicity (Yadav and Khandelwal,
2008). During acute and chronic toxicity picroliv function in three
ways; faster the revival of liver parenchyma cells, stimulates protein
and nucleic acid synthesis and possess immune stimulatory response. It
has also been studied in detail that picroliv has antiviral activity (Tiwari
et al., 2012). Historically, P. kurroa is well reported for traditional and
folk use in the treatment of anaemia, asthma, obesity, malaria, stomach
ache, as an anti-inflammatory agent, a cathartic, a cholagogue, to treat
fever, immune disorders, skin diseases, bronchial asthma, viral hepatitis
(Table 1).
The semisolid alcoholic extract of P. kurroa was used for the for-
mulation of P. kurroa capsules. Each capsule contains 100 mg of con-
centrated extract and using these two times per day reduced number of
hepatic disorders (Saleh, 2007). Vimilin is another herbal product of P.
kurroa accessible to liver patients (Table 2). Rats with artificially in-
duced diabetes were treated with aqueous extract of P. kurroa with dose
range from 100 to 200 mg/kg, p.o. for fourteen days. After treatment,
measurement of blood glucose level and lipid profile shows that plant
extract greatly reduced glucose level of blood and increase the glucose
tolerance (Hussain et al., 2009). The part of P. kurroa concerned with
medication is 1–3 g of the powdered crude drug. No information has
been available regarding P. kurroa extract hypersensitivity (Table 1).
2.19. Solanaceae
2.19.1. Lycium chinense
Lycium chinense Mill. (Solanaceae) traditionally known for pro-
moting long life and hepatoprotective activity. Antihepatotoxic com-
ponent isolated from the berries of L. chinense are kukoamine A, zeax-
anthin and zeaxanthin dipalmitate which act as liver tonic by revival of
normal liver action after toxin exposure. The level of sorbitol dehy-
drogenase (SDH) and glutamic pyruvic transaminase (GPT) sig-
nificantly reduced in response to zeaxanthin dipalmitate (Ahna et al.,
2014).
L. chinense Mill fruit extract (LFE) showed a dose dependent (IC50 =
83.6 μg/ml) radical scavenging effect against CCl4 hepatotoxicity in
rats. The LFE found to have strong antioxidant and enzyme expressional
regulation effect. The LFE also found to lower serum aspartate, alanine
aminotransferase, and alkaline phosphatase (ALP) which is related to
its hepatoprotective function (Ha et al., 2005). No toxicity or not any
side effects till now have been reported for L. chinense hypersensitivity
(Table 1).
116
Journal of Ethnopharmacology 216 (2018) 104–119
2.20. Utricaceae
2.20.1. Boehmeria nivea
Boehmeria nivea (L.) Guadich. (Urticaceae) known as Ramie grass is
a perennial shrub widely spread across China, India, Taiwan, Nepal and
Bhutan (Huang et al., 2006). This plant is a source of fiber for textile
industry. However, it also possesses different medicinal benefits in-
cluding; diuretic, antipyretic, and hepatoprotective. Especially roots are
more effective and clinically tested for the treatment of liver (Table 1).
Bioactive compounds are mainly fatty acids including stearic acid,
boehnic acid, and palmatic acid. Furthermore, rhoifolin isolated from B.
nivea leaves was found to play protective role in liver ailments (Coon
and Ernst, 2004). In the market of medicine triguliv is eminent herbal
formulation of B. nivea (Table 2).
In an animal study (rat model) the effect of variable doses (125,
250, 500 mg/kg) of 80% methanolic extract of B. nivea was screened for
about twenty-one days. The extract amount of 500 mg/kg produce good
results which are proportionate to glibenclamide, taken as reference
drug. The administrated amount of 500 mg/kg reduce FBS (fasting
blood glucose), triglycerides, cholesterol, aspartate, urea level of blood,
aminotransferase, urine ketone and sugar level of urine in diabetic rats
at the end of 21 days. The study suggested the supplementation of diet
with root extract of B. nivea for treating hyperlipidemia, hyperglycemia
and boosting antioxidant system (Sancheti et al., 2011). Not any po-
tential side effect of B. nivea has been reported (Table 1).
3. Short summary
Considering the enormous biodiversity of medicinal plants and the
high incidence of liver complications the present review extensively
focuses on data collected from plants which are claimed as liver pro-
tective agents due their phytoconstituents, part used and herbal for-
mulations. Liver is a vital human organ engaged in recognition and
detoxification of intoxicants. Today, liver is more susceptible to infec-
tion and malfunctioning, consequently, due to increased pollution and
contaminated food than ever. No doubt, various approaches have been
developed to cure liver diseases but still they immunosuppressive or fail
to rehabilitate damaged liver cells completely. In this regard, plants
have been found to be hepatoprotective as they contain potential con-
stituents for the treatment of liver diseases with no or minor side ef-
fects. This review is enlisted with those medicinal plants that have
shown assertive effects in liver treatment especially Hepatitis. Hepatitis
has become a major cause of death in developing and under developed
countries. Herbal treatment as compared to synthetic drugs is preferred
today. That’s why, active components from these plants in purified form
are being used in traditional medicine system to cure Hepatitis and
other liver diseases. These components have been tested in vivo as well
as in vitro with specified amount. Data regarding safety, efficacy, pre-
paration used, extracts and active ingredients of numerous plant species
that have been scientifically evaluated for medical application is
gathered in this review. This data can be further used in countries
where herbal medicines market is poorly regulated, and herbal products
are often neither registered nor controlled. Since large population of the
world is still dependent on conventional therapies because of their low
cost and easy availability. Development of such herbal medicines with
standards of safety and efficacy can revitalise treatment of liver dis-
orders and hepatoprotective activity. A limited knowledge about such
plants drives researchers to search more such plants to cure liver dis-
eases along with other ailments to minimize the use of synthetic drugs.
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