AVS GLOSSARY EXPERIMENTS

5-HETE: 5-Hydroxyeicosatetraenoic acid is an endogenous eicosanoid. 5-HETE is an

intermediate in the pathway of leukotriene synthesis.

Akt: is a serine/threonine protein kinase that plays a key role in multiple cellular processes such
as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration.

BAD: The Bcl-2-associated death promoter protein is a pro-apoptotic member of the Bcl-2 gene
family which is involved in initiating apoptosis.

Beta-catenin: is a protein that in humans is encoded by the CTNNB1 gene. β-catenin is part of a
complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation
and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. β-
catenin also anchors the actin cytoskeleton and may be responsible for transmitting the contact
inhibition signal that causes cells to stop dividing once the epithelial sheet is complete.

Calpain: is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine

proteases (proteolytic enzymes) expressed ubiquitously in mammals and many other organisms.
Although the physiological role of calpains are still poorly understood, they have been shown to
be active participants in processes such as cell mobility and cell cycle progression, as well as
cell-type specific functions such as long-term potentiation in neurons and cell fusion in
myoblasts. Under these physiological conditions, a transient and localized influx of calcium into
the cell activates a small local population of calpains (for example, those close to Ca2+
channels), which then advance the signal transduction pathway by catalyzing the controlled
proteolysis of its target proteins. Other reported roles of calpains are in cell function, helping to
regulate clotting and the diameter of blood vessels, and playing a role in memory. Calpains have
been implicated in apoptotic cell death, and appear to be an essential component of necrosis.

CD95: see FAS ligand

CHOP: is the acronym for a chemotherapy regimen used in the treatment of non-Hodgkin
lymphoma. CHOP stands for cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin
(vincristine), and prednisone/prednisolone.

c-Myc: codes for a protein that binds to the DNA of other genes and is therefore a transcription
factor. When a gene like Myc is altered to cause cancer, the cancerous version of the gene is
called an oncogene. The healthy version of the gene that it is derived from is called a proto-
oncogene.

Cyclin-D1: is a protein that in humans is encoded by the CCND1 gene. The protein encoded by
this gene belongs to the highly conserved cyclin family, whose members are characterized by a
dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as
regulators of CDK kinases which are involved in the regulation of the cell cycle and in the
regulation of transcription and mRNA processing.

Cytokine: are small cell-signaling protein molecules that are secreted by the glial cells of the
nervous system and by numerous cells of the immune system and are a category of signaling
molecules used extensively in intercellular communication. Cytokines can be classified as
proteins, peptides, or glycoproteins; the term "cytokine" encompasses a large and diverse family
of regulators produced throughout the body by cells of diverse embryological origin.

ERKs: extracellular-signal-regulated kinases or classical MAP kinases are widely expressed

protein kinase intracellular signalling molecules which are involved in functions including the
regulation of meiosis, mitosis, and postmitotic functions in differentiated cells. Many different
stimuli, including growth factors, cytokines, virus infection, ligands for heterotrimeric G protein-
coupled receptors, transforming agents, and carcinogens, activate the ERK pathway.

FAS ligand (CD95L): is a type-II transmembrane protein that belongs to the tumor necrosis
factor (TNF) family. Its binding with its receptor induces apoptosis. Fas ligand/receptor
interactions play an important role in the regulation of the immune system and the progression of
cancer.

Fos protein: is a cellular proto-oncogene belonging to the immediate early gene family of
transcription factors.

Freund's adjuvant: is a solution of antigen emulsified in mineral oil and used as an

immunopotentiator (booster). The complete form (CFA or FCA) is composed of inactivated and
dried mycobacteria (usually M. tuberculosis), whereas the incomplete form (IFA or FIA) lacks
the mycobacterial components (hence just the water in oil emulsion). It is named after Jules T.
Freund.

GI50: The concentration needed to reduce the growth of treated cells to half that of untreated
cells.

Glycogen synthase kinase 3 beta: also known as GSK3B, is an enzyme which in humans is
encoded by the GSK3B gene which is involved in energy metabolism, neuronal cell
development, and body pattern formation.

GRP78: glucose-related protein. One of the stress related proteins, identical to endoplasmin.

IC50: The half maximal inhibitory concentration is a measure of the effectiveness of a compound
in inhibiting biological or biochemical function.
IkappaB kinase (IKK): also CHUK, IKBKA, IKBKB, IKK, IKK-1, IKK-2, inhibitor of
NFkappaB kinase, inhibitor of NF-kappaB kinase, STK12, TANK-binding kinase 1, and TBK1
is a human enzyme involved in 15 metabolic pathways related to metabolism: MapK signaling
pathway, apoptosis, Toll-like receptor signaling pathway, T cell receptor signaling pathway, B
cell receptor signaling pathway, Insulin signaling pathway, Adipocytokine signaling pathway,
Type 2 diabetes mellitus, epithelial cell signaling in helicobacter pylori, pancreatic cancer,
prostate cancer, chronic myeloid leukemia, acute myeloid leukemia, and small cell lung cancer.

IL-10: Interleukin-10, also known as human cytokine synthesis inhibitory factor (CSIF), is an
anti-inflammatory cytokine. In humans IL-10 is encoded by the IL10 gene.This cytokine is
produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has
pleiotropic effects in immunoregulation and inflammation. It is capable of inhibiting synthesis of
pro-inflammatory cytokines like IFN-γ, IL-2, IL-3, TNFα and GM-CSF made by cells such as
macrophages and the Type 1 T helper cells. IL-10 also displays potent abilities to suppress the
antigen presentation capacity of antigen presenting cells. However, it is also stimulatory towards
certain T cells, mast cells and stimulates B cell maturation and antibody production.

IL-1beta: interleukin-1 refers to a group of three polypeptides (interleukin-1 alpha (IL-1α),

interleukin-1 beta (IL-1ß) and interleukin-1 receptor antagonist (IL-1Ra)), that play a central role
in the regulation of immune and inflammatory responses.

IL-2: Interleukin-2 is a type of cytokine immune system signaling molecule, which is a

leukocytotrophic hormone that is instrumental in the body's natural response to microbial
infection and in discriminating between foreign (non-self) and self. IL-2 mediates its effects by
binding to IL-2 receptors, which are expressed by lymphocytes, the cells that are responsible for
immunity. IL-2 is necessary for the development of T cell immunologic memory, one of the
unique characteristics of the immune system. IL-2 is also necessary during T cell development in
the thymus for the maturation of a unique subset of T cells that are termed regulatory T cells (T-
regs) which prevent other T cells from recognizing and reacting against "self antigens", which
could result in "autoimmunity".

IL-4: Interleukin-4, is a cytokine that induces differentiation of naive helper T cells (Th0 cells)
to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. It has
many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and
the differentiation of CD4+ T-cells into Th2 cells. It is a key regulator in humoral and adaptive
immunity. IL-4 induces B-cell class switching to IgE, and up-regulates MHC class II production.
Overproduction of IL-4 is associated with allergies.

IL-6: is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is

secreted by T cells and macrophages to stimulate immune response to trauma, especially burns
or other tissue damage leading to inflammation.

Interferon-gamma (IFN-γ): is a dimerized soluble cytokine that is the only member of the type
II class of interferons. IFN-γ, or type II interferon, is a cytokine that is critical for innate and
adaptive immunity against viral and intracellular bacterial infections and for tumor control.
Aberrant IFN-γ expression is associated with a number of autoinflammatory and autoimmune
diseases. The importance of IFN-γ in the immune system stems in part from its ability to inhibit
viral replication directly, and most importantly from its immunostimulatory and
immunomodulatory effects.

JNK: c-Jun N-terminal kinases, originally identified as kinases that bind and phosphorylate c-
Jun on Ser63 and Ser73 within its transcriptional activation domain, are mitogen-activated
protein kinases which are responsive to stress stimuli, such as cytokines, ultraviolet irradiation,
heat shock, and osmotic shock, and are involved in T cell differentiation and apoptosis.

Kd value: a dissociation constant is a specific type of equilibrium constant that measures the
propensity of a larger object to separate (dissociate) reversibly into smaller components, as when
a complex falls apart into its component molecules, or when a salt splits up into its component
ions. The dissociation constant is usually denoted Kd and is the inverse of the association
constant. It is commonly used to describe the affinity between a ligand (such as a drug) and a
protein.

LD50:the median lethal dose, LD50 (abbreviation for “Lethal Dose, 50%”), LC50 (Lethal
Concentration, 50%) or LCt50 (Lethal Concentration & Time) of a toxic substance or radiation is
the dose required to kill half the members of a tested population after a specified test duration.
LD50 figures are frequently used as a general indicator of a substance's acute toxicity. The test
was created by J.W. Trevan in 1927.

Lipopolysaccharides (LPS): also known as lipoglycans, are large molecules consisting of a lipid
and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-
negative bacteria, act as endotoxins and elicit strong immune responses in animals.

LY294002: is a morpholine derivative of quercetin. It is a potent inhibitor of phosphoinositide 3-

kinases (PI3Ks) which are a family of enzymes involved in cellular functions such as cell
growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in
turn are involved in cancer.

MCP-1: Monocyte chemotactic protein-1, a member of the small inducible gene (SIG) family,
plays a role in the recruitment of monocytes to sites of injury and infection. MPC1 has been
found in the joints of people with rheumatoid arthritis where may serve to recruit macrophages
and perpetuate the inflammation in the joints. MPC1 has also been found elevated in the urine of
people with lupus as a sign warning of inflammation of the kidney. MCP1 has also been called
small inducible cytokine A2 (SCYA2) and monocyte chemotactic and activating factor (MCAF).

MCP-3: monocyte chemotactic protein-3 is produced by a variety of tumor cell lines and
regulates protease secretion by macrophages; its production may contribute, therefore, to
invasion and metastasis of cancer cells.

MIP-2: macrophage inflammatory protein-2-gamma is a potent chemoattractant for neutrophils,

and weaker for dendritic cells, known mainly because of its chemotactic activity
Mitogen-activated protein (MAP): kinases are serine/threonine-specific protein kinases that
respond to extracellular stimuli (mitogens, osmotic stress, heat shock and proinflammatory
cytokines) and regulate various cellular activities, such as gene expression, mitosis,
differentiation, proliferation, and cell survival/apoptosis.

mPGES-1: microsomal prostaglandin E synthase-is a key enzyme in the formation of PGE2.

NBT: Nitro blue tetrazolium is a chemical compound composed of two tetrazole moieties. It is
used in immunology for sensitive detection of alkaline phosphatase with 5-Bromo-4-chloro-3-
indolyl phosphate (BCIP). NBT serves as the oxidant and BCIP is the AP-substrate and gives
dark blue dye.

Nuclear factor-kappa B (NF-κB): Is a protein complex that controls the transcription of DNA.
It is found in almost all animal cell types and is involved in cellular responses to stimuli such as
stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral
antigens and plays a key role in regulating the immune response to infection.

p21: also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1 is a protein

that in humans is encoded by the CDKN1A gene located on chromosome 6 (6p21.2). The p21
(WAF1) protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus
functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly
controlled by the tumor suppressor protein p53, through which this protein mediates the p53-
dependent cell cycle G1 phase arrest in response to a variety of stress stimuli.

p38: are a class of mitogen-activated protein kinases which are responsive to stress stimuli, such
as cytokines, ultraviolet irradiation, heat shock, and osmotic shock, and are involved in cell
differentiation and apoptosis.

p53: is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is important
in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor
suppressor that is involved in preventing cancer.

p65: Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit, is a
pleiotropic transcription factor which is present in almost all cell types and is involved in many
biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis
and apoptosis.

PI 3 Kinase: phosphoinositide 3-kinases are a family of enzymes involved in cellular functions

such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking,
which in turn are involved in cancer.

PMBC: a peripheral blood mononuclear cell is any blood cell having a round nucleus; a
lymphocyte, a monocyte or a macrophage. These blood cells are a critical component in the
immune system to fight infection and adapt to intruders.
P-selectin: is a cell adhesion molecule (CAM) on the surfaces of activated endothelial cells,
which line the inner surface of blood vessels, and activated platelets. In unactivated endothelial
cells, it is stored in granules Weibel-Palade bodies, and α-granules in unactivated platelets.
P-selectin plays an essential role in the initial recruitment of leukocytes (white blood cells) to the
site of injury during inflammation. When endothelial cells are activated by molecules such as
histamine or thrombin during inflammation, P-selectin moves from an internal cell location to
the endothelial cell surface.

PUMA: The p53 upregulated modulator of apoptosis, is a pro-apoptotic member of the Bcl-2
protein family. Bcl-2 family members can form hetero- or homodimers, and they act as anti- or
pro-apoptotic regulators that are involved in a wide variety of cellular activities. The expression
of PUMA is regulated by the tumor suppressor p53, and PUMA has been shown to be involved
in p53-mediated apoptosis.

SGPT: Serum glutamic pyruvic transaminase, an enzyme that is normally present in liver and
heart cells. SGPT is released into blood when the liver or heart are damaged. Also called alanine
aminotransferase (ALT).

Sp 1: is a human transcription factor involved in gene expression in the early development of an

organism. Sp1 has been used as a control protein to compare with when studying the increase or
decrease of the aryl hydrocarbon receptor and/or the estrogen receptor, since it binds to both and
generally remains at a relatively constant level.

TF: Transfer factors are immune molecules that cause antigen-specific cell-mediated immunity,
primarily delayed hypersensitivity and the production of lymphokines, as well as binding to the
antigens themselves.

TNF alpha: tumor necrosis factor (cachexin or cachectin and formerly known as tumor necrosis
factor-alpha) is a cytokine involved in systemic inflammation and is a member of a group of
cytokines that stimulate the acute phase reaction.The primary role of TNF is in the regulation of
immune cells. TNF is able to induce apoptotic cell death, to induce inflammation, and to inhibit
tumorigenesis and viral replication.

Topoisomerases: are enzymes that unwind and wind DNA, in order for DNA to control the
synthesis of proteins, and to facilitate DNA replication.

Transaminase: or an aminotransferase is an enzyme that catalyzes a type of reaction between an

amino acid and an α-keto acid. Transamination involves removing the amino group from the
amino acid, leaving behind an α-keto acid, and transferring it to the reactant α-keto acid and
converting it into an amino acid.

VEGF: Vascular endothelial growth factor is a signal protein produced by cells that stimulates
the growth of new blood vessels. It is part of the system that restores the oxygen supply to tissues
when blood circulation is inadequate.
WOMAC: The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a set
of standardized questionnaires used by health professionals to evaluate the condition of patients
with osteoarthritis of the knee and hip. It can be self-administered and was developed at Western
Ontario and McMaster Universities. It assesses the pain, joint stiffness, physical, social &
emotional function of a person with osteoarthritis in determining the overall level of disability.

Wortmannin: a furanosteroid metabolite of the fungi Penicillium funiculosum, Talaromyces

(Penicillium) wortmannii, is a specific, covalent inhibitor of phosphoinositide 3-kinases (PI3Ks)
which are a family of enzymes involved in cellular functions such as cell growth, proliferation,
differentiation, motility, survival and intracellular trafficking, which in turn are involved in
cancer.

Devils claw

5-LOX: Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase

activating protein, or FLAP, is a protein that in humans is encoded by the ALOX5AP gene.
FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of
leukotrienes. It is an integral protein within the nuclear membrane. FLAP is necessary in
synthesis of leukotriene, which are lipid mediators of inflammation that is involved in respiratory
and cardiovascular diseases. FLAP functions as a membrane anchor for 5-lipooxygenase and as
an amine acid-bind protein. How FLAP activates 5-lipooxygenase is not completely understood,
but there is a physical interaction between the two.

AUC: a measure of total drug concentration in the blood plasma over a period of time.

Cochran-Armitage test: named for William Cochran and Peter Armitage, is used in categorical
data analysis when the aim is to assess for the presence of an association between a variable with
two categories and a variable with k categories. It modifies the chi-square test to incorporate a
suspected ordering in the effects of the k categories of the second variable. For example, doses of
a treatment can be ordered as 'low', 'medium', and 'high', and we may suspect that the treatment
benefit cannot become smaller as the dose increases. The trend test is often used as a genotype-
based test for case-control genetic association studies.

COX: Cyclooxygenase is an enzyme that is responsible for formation of important biological

mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane.
Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and
pain. Non-steroidal anti-inflammatory drugs, such as aspirin and ibuprofen, exert their effects
through inhibition of COX. The names "prostaglandin synthase (PHS)" and "prostaglandin
endoperoxide synthetase (PES)" are still used to refer to COX.

COX-2: Cyclooxygenase-2, a protein acts as an enzyme and specifically catalyzes (speeds) the
production of certain chemical messengers called prostaglandins. Some of these messengers are
responsible for promoting inflammation. When Cox-2 activity is blocked, inflammation is
reduced. Unlike cox-1, cox-2 is active only at the site of inflammation, not in the stomach.

DPPH: an organic chemical compound 2,2-diphenyl-1-picrylhydrazyl. It is a dark-colored

crystalline powder composed of stable free-radical molecules. DPPH has two major applications,
both in laboratory research: one is a monitor of chemical reactions involving radicals and another
is a standard of the position and intensity of electron paramagnetic resonance signals.

Freund's adjuvant: is a solution of antigen emulsified in mineral oil and used as an

immunopotentiator (booster). The complete form (CFA or FCA) is composed of inactivated and
dried mycobacteria (usually M. tuberculosis), whereas the incomplete form (IFA or FIA) lacks
the mycobacterial components (hence just the water in oil emulsion). It is named after Jules T.
Freund.

Gene expression: is the process by which information from a gene is used in the synthesis of a
functional gene product. These products are often proteins, but in non-protein coding genes such
as rRNA genes or tRNA genes, the product is a functional RNA. The process of gene expression
is used by all known life - eukaryotes (including multicellular organisms), prokaryotes (bacteria
and archaea) and viruses - to generate the macromolecular machinery for life. Several steps in
the gene expression process may be modulated, including the transcription, RNA splicing,
translation, and post-translational modification of a protein. Gene regulation gives the cell
control over structure and function, and is the basis for cellular differentiation, morphogenesis
and the versatility and adaptability of any organism. Gene regulation may also serve as a
substrate for evolutionary change, since control of the timing, location, and amount of gene
expression can have a profound effect on the functions (actions) of the gene in a cell or in a
multicellular organism.

HAQ: The Health Assessment Questionnaire was originally developed in 1978 by James F.
Fries, MD, and colleagues at Stanford University. It was one of the first self-report functional
status (disability) measures and has become the dominant instrument in many disease areas,
including arthritis. It is widely used throughout the world and has become a mandated outcome
measure for clinical trials in rheumatoid arthritis and some other diseases.

Hot Plate Test: Mice are brought to the testing room and allowed to acclimatize for 10 minutes
before the test begins. Pain reflexes in response to a thermal stimulus are measured using a Hot
Plate Analgesia Meter. The surface of the hot plate is heated to a constant temperature of 55oC,
as measured by a built-in digital thermometer with an accuracy of 0.1oC and verified by a surface
thermometer. Mice are placed on the hot plate (25.4 cm x 25.4 cm), which is surrounded by a
clear acrylic cage (19 cm tall, open top), and the Start/Stop button on the timer is activated. The
latency to respond with either a hindpaw lick, hindpaw flick, or jump (which ever comes first) is
measured to the nearest 0.1 seconds by deactivating the timer when the response is observed.
The mouse is immediately removed from the hot plate and returned to its home cage. If a mouse
does not respond within 30 seconds, the test is terminated and the mouse is removed from the hot
plate. Animals are tested one at a time and are not habituated to the apparatus prior to testing.
Each animal is tested only once.
IL-1beta: interleukin-1 refers to a group of three polypeptides (interleukin-1 alpha (IL-1α),
interleukin-1 beta (IL-1ß) and interleukin-1 receptor antagonist (IL-1Ra)), that play a central role
in the regulation of immune and inflammatory responses.

IL-6: is an interleukin that acts as both a pro-inflammatory and anti-inflammatory cytokine. It is

secreted by T cells and macrophages to stimulate immune response to trauma, especially burns
or other tissue damage leading to inflammation.

iNOS: Nitric oxide synthases are a family of eukaryotic enzymes that catalyze the production of
nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule, having a vital
role in many biological processes. NOS is an enzyme in the body that contributes to transmission
from one neuron to another, to the immune system and to dilating blood vessels. It does so by
synthesis of nitric oxide (NO) from the terminal nitrogen atom of arginine in the presence of
NADPH and dioxygen (O2). NOS is the only known enzyme that binds flavin adenine
dinucleotide (FAD), flavin mononucleotide (FMN), heme, tetrahydrobiopterin (BH4) and
calmodulin.

Interleukin-1[beta]IL-1beta: interleukin-1 refers to a group of three polypeptides (interleukin-1

alpha (IL-1α), interleukin-1 beta (IL-1ß) and interleukin-1 receptor antagonist (IL-1Ra)), that
play a central role in the regulation of immune and inflammatory responses.

LD50:the median lethal dose, LD50 (abbreviation for “Lethal Dose, 50%”), LC50 (Lethal
Concentration, 50%) or LCt50 (Lethal Concentration & Time) of a toxic substance or radiation is
the dose required to kill half the members of a tested population after a specified test duration.
LD50 figures are frequently used as a general indicator of a substance's acute toxicity. The test
was created by J.W. Trevan in 1927.

Lequesne index: is a 10-question interview-style survey given to patients with osteoarthritis of

the knee. It has 5 questions pertaining to pain or discomfort, 1 question dealing with maximum
distance walked, and 4 questions about activities of daily living. The total questionnaire is scored
on a 0 to 24 scale, with lower scores meaning less functional impairment.

Leukotrienes are fatty molecules of the immune system that contribute to inflammation in
asthma and allergic rhinitis. Leukotriene antagonists are used to treat these diseases.
Leukotrienes are naturally produced eicosanoid lipid mediators. Leukotrienes use both autocrine
signalling and paracrine signalling to regulate the body's response. Leukotrienes are produced in
the body from arachidonic acid by the enzyme 5-lipoxygenase. Their production usually
accompanies the production of histamine. Leukotrienes produced within a cell convey signals
that act either on the cell producing them (autocrine signalling) or on neighboring cells
(paracrine signalling) to regulate the immune response.

Lipopolysaccharides (LPS): also known as lipoglycans, are large molecules consisting of a lipid
and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-
negative bacteria, act as endotoxins and elicit strong immune responses in animals.
MMPs: Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are
adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known
as the metzincin superfamily. Collectively they are capable of degrading all kinds of extracellular
matrix proteins, but also can process a number of bioactive molecules. They are known to be
involved in the cleavage of cell surface receptors, the release of apoptotic ligands (such as the
FAS ligand), and chemokine/cytokine in/activation. MMPs are also thought to play a major role
on cell behaviors such as cell proliferation, migration (adhesion/dispersion), differentiation,
angiogenesis, apoptosis and host defense.

Nitric oxide (NO): Nitric oxide (common name) or nitrogen monoxide (systematic name) is a
chemical compound with chemical formula NO. This gas is an important signaling molecule in
the body of mammals, including humans. NO is an important messenger molecule involved in
many physiological and pathological processes within the mammalian body both beneficial and
detrimental. Appropriate levels of NO production are important in protecting an organ such as
the liver from ischemic damage. However sustained levels of NO production result in direct
tissue toxicity and contribute to the vascular collapse associated with septic shock, whereas
chronic expression of NO is associated with various carcinomas and inflammatory conditions
including juvenile diabetes, multiple sclerosis, arthritis and ulcerative colitis.

Nuclear factor-kappa B (NF-κB): Is a protein complex that controls the transcription of DNA.
It is found in almost all animal cell types and is involved in cellular responses to stimuli such as
stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral
antigens and plays a key role in regulating the immune response to infection.

Permeation: in physics and engineering, is the penetration of a permeate (such as a liquid, gas,
or vapor) through a solid, and is related to a material's intrinsic permeability. Permeability is
tested by permeation measurement, for example by a minipermeameter.

p-value: In statistical significance testing, the p-value is the probability of obtaining a test
statistic at least as extreme as the one that was actually observed, assuming that the null
hypothesis is true. A closely related concept is the E-value, which is the average number of times
in multiple testing that one expects to obtain a test statistic at least as extreme as the one that was
actually observed, assuming that the null hypothesis is true. When the tests are statistically
independent the E-value is the product of the number of tests and the p-value. The lower the p-
value, the less likely the result is if the null hypothesis is true, and consequently the more
"significant" the result is, in the sense of statistical significance. One often accepts the alternative
hypothesis, (i.e. rejects a null hypothesis) if the p-value is less than 0.05 or 0.01, corresponding
respectively to a 5% or 1% chance of rejecting the null hypothesis when it is true.

Tail-flick Test: The Tail Flick Test is used to measure a rodent’s sensitivity to changing
temperature.  The test subject is restrained in a conical polypropylene tube with an opening
through which its tail is exposed.  In one version of the test, the tail is exposed to a heat lamp and
the amount of time taken for the animal to move (flick) its tail away from the heat is recorded. 
Another version of the tail flick test is the water immersion method.  In that test, approximately
one third of the rodent’s tail from the tip is immersed into a 52OC ± 0.2 water bath and the
amount of time until the rodent flicks or removes its tail is recorded. 
TNF alpha: tumor necrosis factor (cachexin or cachectin and formerly known as tumor necrosis
factor-alpha) is a cytokine involved in systemic inflammation and is a member of a group of
cytokines that stimulate the acute phase reaction.The primary role of TNF is in the regulation of
immune cells. TNF is able to induce apoptotic cell death, to induce inflammation, and to inhibit
tumorigenesis and viral replication.

VAS: A visual analogue scale is a psychometric response scale which can be used in
questionnaires. It is a measurement instrument for subjective characteristics or attitudes that
cannot be directly measured. When responding to a VAS item, respondents specify their level of
agreement to a statement by indicating a position along a continuous line between two end-
points. This continuous (or "analogue") aspect of the scale differentiates it from discrete scales
such as the Likert scale.

WOMAC: The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a set
of standardized questionnaires used by health professionals to evaluate the condition of patients
with osteoarthritis of the knee and hip. It can be self-administered and was developed at Western
Ontario and McMaster Universities. It assesses the pain, joint stiffness, physical, social &
emotional function of a person with osteoarthritis in determining the overall level of disability.

Crataeva nurvala

12-O-tetradecanoyl-phorbol acetate (TPA): also commonly known as tetradecanoylphorbol

acetate, tetradecanoyl phorbol acetate, and phorbol 12-myristate 13-acetate (PMA), is diester of
phorbol and a potent tumor promoter often employed in biomedical research to activate the
signal transduction enzyme protein kinase C (PKC).

Alkaline phosphatase (ALP, ALKP): is a hydrolase enzyme responsible for removing

phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids.
The process of removing the phosphate group is called dephosphorylation. As the name
suggests, alkaline phosphatases are most effective in an alkaline environment. It is sometimes
used synonymously as basic phosphatase. Normal: 30-120 U/L. High ALP levels can show that
the bile ducts are blocked or cholestasis. Also, other related conditions, like bile duct
inflammation (cholecystitis), cholangitis, fatty liver, hepatitis and various other infectious and
non-infectious diseases and conditions of the liver. Other diseases that affect the skeletal system
also reflect in these test results, as high alkaline phosphatase levels may also signify the presence
of Paget's disease, renal osteodystrophy, fractured bone, osteomalacia, rickets,
hyperparathyroidism etc. Other conditions included in the differential diagnosis also include
pregnancy, myelofibrosis, polycythemia vera, seminoma etc.
Ayurveda: Ayurvedic medicine is a system of traditional medicine native to the Indian
subcontinent and practiced in other parts of the world as a form of alternative medicine. In
Sanskrit, the word ayurveda consists of the words āyus, meaning "longevity", and veda, meaning
"related to knowledge" or "science".

Beta-glucuronidases: are members of the glycosidase family of enzymes that catalyze

breakdown of complex carbohydrates. Human β-glucuronidase is a type of glucuronidase that
catalyzes hydrolysis of β-D-glucuronic acid residues from the non-reducing end of
mucopolysaccharides such as heparan sulfate. Human β-glucuronidase is located in the
lysosome. In the gut, brush border β-glucuronidase converts unconjugated bilirubin to the
conjugated form for reabsorption. β-glucuronidase is also present in breast milk, and its action
contributes to neonatal jaundice. Deficiencies in β-glucuronidase result in the non recessive
inherited metabolic disease known as Sly syndrome.

Cyclophosphamide: A synthetic alkylating agent chemically related to the nitrogen mustards

with antineoplastic and immunosuppressive activities. In the liver, cyclophosphamide is
converted to the active metabolites aldophosphamide and phosphoramide mustard, which bind to
DNA, thereby inhibiting DNA replication and initiating cell death.

Detrusor contraction: Normal coordinated function of the bladder with sustained contractions
of the bladder matched by simultaneous relaxation of the sphincteric outlet mechanisms to empty
the bladder.

Gamma-glutamyltransferase or gamma-glutamyl transpeptidase (also γ-

glutamyltransferase, GGT, GGTP, gamma-GT): is an enzyme that transfers gamma-glutamyl
functional groups. High concentrations of GGT are found in renal, prostatic, pancreatic, and
hepatobiliary tissue; smaller amounts are found in all other tissues except muscle. A test that
measures the amount of GGT in the blood is used to detect diseases of the liver, bile ducts, and
kidney; and to differentiate liver or bile duct (hepatobiliary) disorders from bone disease.
Normal: 0-30 U/L. Elevated levels of GGT may indicate congestive heart failure, cholestasis,
cirrhosis, hepatitis, liver ischemia, liver necrosis, liver tumor, chronic pancreatitis, hepatotoxic
drugs. Serum GGT levels are also related to insulin sensitivity and secretion in patients with
abnormal glucose regulation.

Glycolate oxidase (or (S)-2-hydroxy-acid oxidase): This enzyme belongs to the family of
oxidoreductases, specifically those acting on the CH-OH group of donor with oxygen as
acceptor. This enzyme participates in glyoxylate and dicarboxylate metabolism. It employs one
cofactor, Flavin mononucleotide (FMN).

Glycolic acid (or hydroxyacetic acid): is the smallest α-hydroxy acid (AHA). This colorless,
odorless, and hygroscopic crystalline solid is highly soluble in water. It is metabolized to oxalic
acid, which makes it dangerous if ingested. It is a strong irritant.

Hyperoxaluria: is defined as excessive urinary oxalate, is a common abnormal finding in

patients with calcium oxalate kidney stones.
Interleukin-1β (IL-1 β): refers to a group of three polypeptides (interleukin-1 alpha (IL-1α),
interleukin-1 beta (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra)), that play a central role
in the regulation of immune and inflammatory responses.

Lactate dehydrogenase (LDH): An enzyme that catalyzes the conversion of lactate to pyruvate.
This is an important step in energy production in cells. Many different types of cells in the body
contain this enzyme. Some of the organs relatively rich in LDH are the heart, kidney, liver, and
muscle. As cells die, their LDH is released and finds its way into the blood. Normal LDH levels
vary with age, being higher in childhood due to bone growth. Analysis of LDH has not been
standardized and normal ranges vary greatly between laboratories. Generally, the upper limit of
normal for adults is in the range of 200 units/liter. Nearly every type of cancer, as well as many
other diseases, can cause LDH levels to be elevated. LDH levels can be used to monitor
treatment of some cancers, including testicular cancer, Ewing's sarcoma, non-Hodgkin's
lymphoma, and some types of leukemia. Elevated LDH levels can be caused by a number of
noncancerous conditions, including heart failure, hypothyroidism, anemia, kidney disease,
pancreatitis, infectious mononucleosis, and lung or liver disease.

Na+/K+-ATPase: also known as the Na+/K+ pump, sodium-potassium pump, or simply sodium
pump, for short, is an enzyme located in the plasma membrane (to be specific, an electrogenic
transmembrane ATPase) in all animals. The Na+/K+-ATPase helps maintain resting potential,
avail transport, and regulate cellular volume.[citation needed] It also functions as signal
transducer/integrator to regulate MAPK pathway, ROS, as well as intracellular calcium. For
most animal cells, the Na+/K+-ATPase is responsible for 1/3 of the cell's energy expenditure.
For neurons, the Na+/K+-ATPase is responsible for 2/3 of the cell's energy expenditure.

N-acetyl beta-D glucosaminidase: catalyzes the hydrolysis of terminal, non-reducing 2-

acetamido-2-deoxy-beta-glucose residues in chitobiose and higher analogs as well as in
glycoproteins. Has been used widely in structural studies on bacterial cell walls and in the study
of diseases such as mucolipidosis and various inflammatory disorders of muscle and connective
tissue. It cannot pass into glomerular ultrafiltrate due to its high molecular weight. However, this
enzyme shows high activity in renal proximal tubular cells, and leaks into the tubular fluid as the
ultrafiltrate passes through proximal tubules. When proximal tubular cells are injured due to to
any disease process including glomerular proteinuria, nephrolithiasis, hyperglycemia, interstitial
nephritis, transplant rejection or nephrotoxic agents such as antibiotics, antiepileptics, or
radiocontrast agents, its urine level increases and thus is used as a reflection of proximal tubular
cell necrosis.

Oxalate (ethanedioate): sometimes abbreviated as ox when a ligand, is the dianion with formula
C2O42− also written (COO)22−. Many metal ions form insoluble precipitates with oxalate, a
prominent example being calcium oxalate, the primary constituent of the most common kind of
kidney stones. Those with kidney disorders, gout, rheumatoid arthritis, or certain forms of
chronic vulvar pain (vulvodynia) are typically advised to avoid foods high in oxalic acid. The
calcium oxalate crystals or precipitate and can obstruct the kidney tubules. An estimated 80% of
kidney stones are formed from calcium oxalate.
Prostaglandin E2 (PGE2): One of the prostaglandins, a group of hormone-like substances that
participate in a wide range of body functions such as the contraction and relaxation of smooth
muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation
of inflammation. Prostaglandin E2 (PGE-2) is released by blood vessel walls in response to
infection or inflammation that acts on the brain to induce fever. The enzyme mPGES-1 is
involved in the production of PGE2 and is an important "switch" for activating the fever
response.

p-value: In statistical significance testing, the p-value is the probability of obtaining a test
statistic at least as extreme as the one that was actually observed, assuming that the null
hypothesis is true. A closely related concept is the E-value, which is the average number of times
in multiple testing that one expects to obtain a test statistic at least as extreme as the one that was
actually observed, assuming that the null hypothesis is true. When the tests are statistically
independent the E-value is the product of the number of tests and the p-value. The lower the p-
value, the less likely the result is if the null hypothesis is true, and consequently the more
"significant" the result is, in the sense of statistical significance. One often accepts the alternative
hypothesis, (i.e. rejects a null hypothesis) if the p-value is less than 0.05 or 0.01, corresponding
respectively to a 5% or 1% chance of rejecting the null hypothesis when it is true.

Pyrophosphatase (or inorganic pyrophosphatase): is an enzyme that catalyzes the conversion

of one molecule of pyrophosphate to two phosphate ions. The functionality of this enzyme plays
a critical role in lipid metabolism (including lipid synthesis and degradation), calcium absorption
and bone formation, and DNA synthesis, as well as other biochemical transformations.

TNF alpha: tumor necrosis factor (cachexin or cachectin and formerly known as tumor necrosis
factor-alpha) is a cytokine involved in systemic inflammation and is a member of a group of
cytokines that stimulate the acute phase reaction.The primary role of TNF is in the regulation of
immune cells. TNF is able to induce apoptotic cell death, to induce inflammation, and to inhibit
tumorigenesis and viral replication.

Triterpenes: are terpenes consisting of six isoprene units and have the molecular formula C30H48.
The pentacyclic triterpenes can be classified into lupane, oleanane or ursane groups.