HEPATOPROTECTIVE ACTIVITY A REVIEW

About Author:
SOWJANYA GUDUGUNTLA,
M.Pharmacy, Pharmaceutical Chemistry department
ANNAMACHRYA COLLEGE OF PHARMACY,
RAJAMPET, KADAPA Dist, A.P, INDIA.
Sowjanya09.pharma@gmail.com

1. INTRODUCTION:
The Greek word for liver is hepar, so medicinal terms related to liver often start with hepato or hepatic. Liver plays a pivotal role in metabolism, secretion and storage and is sometimes referred as the “ great chemical factory” of the  body, because the body depends on the liver to regulate, synthesize, store and secrete many important proteins, nutrients, chemicals and to purify and clear toxins or unnecessary  substances  from the body¹ . The bile secreted by the liver, among other things, plays an important role in digestion. The risk of the liver intoxication has recently increased by the higher exposure to environmental toxins, pesticides and frequent use of chemotherapeutics.

REFERENCE ID: PHARMATUTOR-ART-1701

Liver damage is always associated with cellular necrosis, increase in tissue lipid peroxidation  and depletion in the tissue glutathione (GSH) levels. In addition, serum levels of many biochemical markers like serum glutamate oxaloacetate transaminase (SGOT/AST) and serum glutamate pyruvate transaminase (SGPT/ALT) triglycerides, cholesterol, bilirubin and alkaline phosphatase are elevated ^2,3.

The following are some of the liver diseases that are commonly observed.
a) Necrosis
b) Cirrhosis
c) Hepatitis- may be of viral, toxic or deficiency type.
d) Hepatic failure - Acute or chronic
e) Liver disorders due to impaired metabolic function. Generally the disorders associated with fat (liposis) and bilirubin (jaundice) metabolisms are very commonly seen.
1. Disorders associated with fat metabolism: Fatty Liver
2. Disorders associated with bilirubin metabolism: jaundice or which may be of different types based upon mechanisms of action and etiology.
i. Hemolytic/Pre-hepatic jaundice.
ii. Obstructive (post-hepatic / cholestatic jaundice)
iii. Hepatogenous/ hepatic jaundice/cholestasis.
In these three conditions there occurs unconjugated hyperbilirubinaemia.
iv.  Hereditary jaundice or pure cholestasis: Gilbert’s syndrome, Dubin Johnson syndrome       and   Crigler-Najjar syndrome etc, Rotor’s syndrome  are some of the hereditary jaundice types.   

f) Chemical/Drug induced hepatotoxicity: Generally may be hepatitis, jaundice   and carcinogenesis.

1.1. HEPATOTOXICITY:
Hepatotoxin is atoxic chemical substance which damages the liver. Toxic liver injury produced by drugs and chemicals may virtually mimic any form of naturally occurring liver disease. Hepatoprotective effect was studied against chemicals and drugs induced hepatotoxicity in rats like alcohol, carbon tetrachloride, galactosamine, paracetamol, isoniazid and rifampicin, antibiotics, peroxidised oil, aflatoxin etc.

Severity of hepatotoxicity is greatly increased if the drug is continued after symptoms develop. Among the various inorganic compounds producing hepatotoxicity are arsenic, phosphorus, copper and iron. The organic agents include certain naturally occuring plant toxins such as pyrrolizidine alkaloids, myotoxins and bacterial toxins.

Liver injury caused by hepatotoxins, such as carbon tetra chloride (CCl₄), ethanol and acetaminophen, is characterised by varying degrees of hepatocyte degeneration and cell death via either apoptosis or necrosis. The generation of reactive intermediate metabolites from the metabolism of hepatotoxins  and the occurrence of reactive oxygen species (ROS) during the inflammatory reaction,  account for a variety of pathophysiologic pathways  leading to cell death, such as covalent binding, disordered cytosolic calcium homeostasis, GSH depletion, onset of mitochondrial permeability transition (MPT) and associated lipid peroxidation. The metabolism of hepatotoxins by cytochrome P-450 enzyme subtypes is a key step of the intoxication; therefore, enzyme inhibitors are shown to minimize the hepatotoxin-associated liver damage. Moreover, substantial evidence exists that MPT is involved in ROS-associated hepatocellular injury and new findings offer a novel therapeutic approach to attenuate cell damage by blocking the onset of MPT. Thus, oxidant stress and lipid peroxidation are crucial elements leading to hepatotoxin-associated liver injury. In addition to specific treatment for a given hepatotoxin, the general strategy for prevention and treatment of the damage includes reducing the production of reactive metabolites of the hepatotoxins, using anti-oxidative agents and selectively targeting therapeutics to Kupffer cells or hepatocytes for on-going processes, which play a role in mediating a second phase of the injury⁴ .

1.2. CLASSIFICATION OF HEPATOTOXINS:

A.Intrinsic
It consists of agents that are predictable hepatotoxins. They are recognized by high incidence of hepatic injury exposed individuals and in experimental animals. There is a consistant latent period between exposure to a particular agent and the development of hepatic injury and the injury appeared to be dose related^5,6.There are two types of intrinsic hepatotoxins:

1.Direct hepatotoxins:
It may be so called because they (metabolic products) produce direct injury to hepatocytes and its organelles, especially the endoplasmic reticulum. CCl₄, the prototype, produces peroxidation of the membrane lipids and other chemicals that lead to degeneration of the membranes.

2. Indirect hepatotoxins:
They are anti-metabolites and related compounds that produce hepatic injury by interference with the specific metabolic pathway or processes. The structural injury produced by indirect hepatotoxins, appear to be secondary to a metabolic region. While in that produced by direct hepatotoxins,  the metabolic dearrangement is secondary to the structural injury. The hepatic damage produced by indirect hepatotoxins may be mainly cytotoxic injury (by interfering with metabolic pathway or processes essential for parenchyma integrity) expressed as steatiosis or necrosis, or may be mainly cholestasis, interfering only or mainly with biliary secretion.

 B. Host idiosyncrasy:
It consists of agents that are not predictably hepatotoxic, but produces hepatic injury in only a small portion of exposed individual. Who are uniquely susceptible. In several instances auto antibodies directed against normal cellular constituents are detected. The injury does not appear to be dose related and is not reproducible in experimental animals and appears after a variable latent period^6,7 .

1.3. EVALUATION of HEPATOPROTECTIVE ACTIVITY:
A review of literature reveals that several chemical substances and drugs having specific actions on liver are used as hepatotoxins in experimental animals to simulate ideal diseased conditions. The hepatoprotective activity can be most easily evaluated /screened with the aid of several model systems of liver damage in experimental animals.

In all test model systems, conditions for liver damage are implemented and an attempt is made to counteract this toxicosis with the substance/preparation under test. The magnitude of the protective effect can be measured by estimating the enzyme activities and the rate of survival and can be verified histologically. The available methods are in vivo, ex vivo and in vitro methods⁸ . All these methods are used to study the protective or curative effects of any compound under test. In order to test for hepatoprotective activity the test substance and the hepatotoxin are administered simultaneously whereas in case of antihepatotoxic or curative activity the test substance is generally administered after induction of hepatotoxicity

a.      In vitromethods:
Hepatocytes are generally isolated by using in-situ, two step recirculating collagenase perfusion technique. These are then seeded in small containers and exposed to test samples and toxins. After a specified time period, the degree of toxicity or protection is assessed by viability tests and enzyme levels such as GOT and GPT. By employing primary culture hepatocytes  using  CCl₄, galactosamine, thioacetamide, ethanol, paracetamol (PCML) etc. as hepatotoxins several hepatoprotective screening models have been devised. These have a number of advantages over in vivo methods such as their ability to dispose numerous samples at a time, low cost with a small size, little variation  and reproducibility of results. The major disadvantage is that sometimes it may not reflect the events which occur in animals.

b.      Ex- vivo models:
In this model, after completion of preselected in vivo test protocol hepatocytes are isolated and the percentage of viable cells and biochemical parameters are determined as liver function tests. These methods are somewhat better correlated to clinical models than in vitro or in vivo methods.

c.       In vivomethods:
This method is used not only to study the nature of the given compound but also to study the mechanism of the toxicant. Hepatotoxicity  is produced  in experimental animals by the administration of  known dose of  hepatotoxins like CCl₄, galactosamine, thioacetamide, ethanol and paracetamol etc., which produce marked measurable  effects, the magnitude of which can be measured by carrying out various liver function tests viz. morphological, metabolic or functional, biochemical and histopathological  determinations.  Although it is a very convenient laboratory method, reproducibility of results is rather poor. The compounds having hepatoprotective claims are also  evaluated in general for their choleretic or anticholestatic activity in order to know whether the liver disorder is due to an abnormality of bilirubin metabolism or not. Choleretics are those agents which increase the out puts of bile by stimulating the liver where as anticholestatics are those which correct the retention and accumulation of bile due to intrinsic and extrinsic factors in the liver. These activities are evaluated by studying bile flow content in conscious and anaesthetized animals for 5 hours.

1.4 .Experimental modelS for hepatoprotectivE SCREENING:
Several chemical reagents and drugs which induce liposis, necrosis, cirrhosis, carcinogenesis and hepatobiliary dysfunctions in experimental animals are classified as hepatotoxins. The following are some of the experimental models explained by employing some of the important hepatotoxins.

1.      CCl₄ model:
A number of CCl₄ models are devised depending upon its dosage through different routes of administration.
a)      Acute hepatic damage: Acute liver damage, characterized by ischemia, hydropic degeneration and central necrosis is caused by oral or subcutaneous administration of CCl₄ (1.25ml/kg). The maximum elevation of biochemical parameters are found to be 24 hours after the CCl₄ administration normally administered as 50% v/v solution in liquid paraffin or olive oil⁹ .
b)      Chronic reversible hepatic damage: Administration of CCl₄ (1ml/kg S.C.) twice weekly for 8 weeks produces chronic, reversible liver damage ¹⁰.
c)      Chronic, irreversible hepatic damage: Administration of CCl₄ (1ml/kg S.C.) twice weekly for 12 weeks simulates chronic, irreversible liver damage¹¹.

2.Thioacetamide model:Thioacetamide (100mg/kg s.c.) induces acute hepatic damage after 48 hrs of administration by causing sinusoidal congestion and hydropic swelling with increased mitosis¹².

3.D-galactosamine model: D-galactosamine (800mg/kg i.p.) induces acute hepatotoxocity after 48 hrs of  administration with diffused necrosis and steatosis¹³.

4 .Paracetamol model:
Paracetamol induces acute hepatotoxicity depending upon its dosage through different routes of administration, such as
a. Paracetamol (800mg/kg i.p.) induces centrilobular necrosis without  steatosis ¹⁴.
b.Paracetamol at a single dose of 3g/kg p.o. stimulates acute hepatic damage. It takes 48 hrs to induce the toxicity¹⁵.

5.Chloroform model:
It produces hepatotoxicity with extensive central necrosis, fatty metamorphosis, hepatic cell degeneration and necrosis either by inhalation or by subcutaneous administration (0.4-1.5ml/kg)¹⁶ .

6.Ethanol model:
Ethanol induces liposis to a different degree depending upon its dose, route and period of administration as follows:
a.  A single dose of ethanol (1ml/kg) induces fatty degeneration¹⁷.
b. Administration of 40%v/v ethanol (2 ml/100g/day p.o.) for 21 days produces fatty liver¹⁸.
c.  Administration  of country made liquor (3ml/100 g/day p.o.) for 21 days produces liposis¹⁹.

Paracetamol induced hepatotoxicity
Paracetamol or acetaminophen (N-acetyl-P-aminophenol, APAP) induced hepatic injuries are commonly used models  for screening of hepatoprotective  drugs ^20,21 and it causes acute centrilobular necrosis in rats, mice, guinea pig, hamsters, rabbits, cats, dogs and²² pigs and centrizonal heamorrhagic necrosis in humans mostly characterized by pyknosis and eosinophilic cytoplasm^22,23 .

Paracetamol is one of the most widely used drug ²⁴ for   analgesic and antipyretic activity worldwide. It is one of the most common pharmaceutical associated with both intentional and accidental poisoning. It is a major cause of liver failure and causes death when taken in excess ²⁵  and is assumed to be safe in recommended doses. It produces hepatic necrosis at higher doses²² . Paracetamol is rapidly absorbed from the stomach and small intestine and metabolized by conjugation in the liver to non-toxic agents. Therapeutic doses of drug are metabolized mostly to sulphate and glucuronide conjugates. The rest is metabolized to a reactive intermediate which is detoxified by conjugation with glutathione. In acute overdose or when the maximum daily dose is exceeded over a prolonged period, the normal conjugative pathway of metabolism becomes saturated. Excess paracetamol is then oxidatively metabolized in the liver via the mixed function oxidase P450 system to a toxic metabolite N-acetyl-P-benzo-quinoneimine (NAPQI).  NAPQI has extremely, short half-life and is rapidly conjugated with glutathione, a sulphydryl donor. Under conditions of excessive NAPQI formation or reduced glutathione store, NAPQI covalently binds to vital proteins and the lipid bilayer of hepatocyte membranes. The result is hepatocellular death and centrilobular liver necrosis²⁵ . Small doses are eliminated by conjugation followed by excretion but when the conjugation enzymes are saturated, the drug is diverted to an alternative metabolic pathway, resulting in the formation of a hydroxylamine derivative by cytochrome P450 enzyme. The hydroxylamine derivative, a reactive electrophilic agent, reacts non-enzymatically with glutathione reacts with macromolecules and disrupts their structure and function. Extensive liver damage by paracetamol itself decreases its rate of metabolism and other substrates for hepatic microsomal enzymes. Induction of cytochrome P450 or depletion of hepatic glutathione is a prerequisite for paracetamol-induced toxicity²⁶ . In over dose, the sulphate and glucuronide conjugation pathways are saturated and more drugs are converted to the reactive metabolite. The glutathione available for its detoxification is rapidly depleted and the metabolites accumulated bind covalently to liver cell proteins, causing irreversible damage. Liver damage can be prevented by providing glutathione like substances, such as acetylcysteine, so that the reactive metabolite can be removed by conjugation and the liver cells are protected²⁷.

An alternative view is that oxidative stress has a role in hepatotoxicity. There are many characteristic features of oxidative stress in APAP hepatotoxicity, including lipid peroxidation, mitochondrial damage, ATP depletion, and formation of nitrotyrosine adducts in proteins, presumably owing to formation of superoxide-derived peroxynitrite²⁸ .However, these processes may be consequences of the damage  mediated by protein adduction rather than the direct effect of hepatotoxicity²⁹ .

 

Analysis of bio-chemical parameters to assess liver function
In keeping with the multiplicity of the liver function, a variety of tests are available to assess them. The choice of the test is influenced by its simplicity, reliability and sensitivity as well as the particular function, one is interested in assessing³⁰ .

1.      Serum enzyme parameters:
Transaminases  ³¹
A.Transamination is a process in which an amino group is transferred from an amino acid to an alpha- keto acid. It is an important step in the metabolism of amino acids. The enzyme responsible for  transamination  are called transaminases or amino-transferases. Two diagnostically useful transaminases are glutamate oxaloacetate transaminase SGOT/AST and glutamate pyruvate transaminase SGPT/ALT. These two enzymes are sensitive markers of hepato-cellular injury.

A.    Estimation of SGOT/AST:
SGOT is an enzyme found mainly in heart muscle, liver cells, skeletal muscle and kidneys. Injury to these tissues results in the release of the enzyme in blood. Elevated levels are found in myocardial infarction, cardiac operations, hepatitis, cirrhosis, acute pancreatitis, acute renal diseases and primary muscle diseases. Decreased levels may be found in pregnancy, Beri Beri and Diabetic ketoacidosis. Its normal serum level is 5-40 units/l.

Principle:
SGOT (AST) catalyzes the transfer of amino group between L-Aspartate and a Ketoglutarate to form Oxaloacetate and Glutamate. The Oxaloacetate formed reacts with NADH in the presence of Malate Dehydrogenase to form NAD. The rate of oxidation of NADH to NAD is measured as a decrease in absorbance which is proportional to the SGOT (AST) activity in the sample.

                                                    AST
L-Aspartate + α-ketoglutarate -------------->   Oxaloacetate +L-Glutamate

                                        MDH
Oxaloacetate+ NADH+H⁺ --------------> L- Malate + NAD⁺

SGOT levels are 10-200 fold elevated in patients with acute hepatic necrosis, viral hepatitis and drug induced poisoning. SGOT levels are also elevated by 10 fold in patients of post hepatic jaundice, intra hepatic cholestasis and less than 10 fold in alcoholic and hepatic steatosis. Very high levels are seen in extensive acute hepatic necrosis such as in severe viral hepatitis and acute cholestasis.

B.Estimation of ALT/SGPT:

ALT or SGPT is a cytosolic enzyme primarily present in the liver. Its normal serum level is 7-56 units/l.

Principle:

SGPT (ALT) catalyzes the transfer of amino group from L- alanine to alpha- ketoglutarate to yield pyruvate and L-glutamate. Lactate dehydrogenase then converts pyruvate and NADH into lactate and NAD. The conversion of  NADH to NAD decreases the absorption at 340 nm. The rate of decrease in absorbance is measured and is proportional to the SGPT activity.    

                                            ALT
L-alanine +α-ketoglutarate  --------------> pyruvate +L-Glutamate

 

                                   LDH
Pyruvate +NADH+H⁺  --------------> L-Lactate +NAD⁺

ALT activity is predominantly associated with liver tissues followed by comparatively lower levels in heart, muscles and kidneys.  Quantitation of ALT is a useful parameter in evaluating liver function.  Elevated levels of this enzyme are found in liver and kidney diseases such as infectious or toxic hepatitis, infectious mononucleosis and cirrhosis. Moderate increase is also found in obstructive jaundice, metastasis carcinoma, hepatic congestion and myocardial infarction.

Phosphatases ³¹
Phosphatases belong to the class of enzyme called hydrolases and they are characterized by their ability to hydrolyse a large variety of organic phosphate with the formation of an alcohol and phosphate ions.

Phosphatases of diagnostic significance are alkaline phosphatase and acid phosphatase. These are differentiated by their reaction in alkaline and acidic medium. The P_H for measuring the alkaline phosphatase activity is 10 and for acid phosphatase is 5.

Alkaline phosphatase (ALP) ^2,32,33
ALP is a membrane bound glycoprotein enzyme, produced by many tissues, especially bone, liver, intestine, placenta and is excreted into the bile. Elevation in activity of the enzyme can thus be found in diseases of bone, liver and in pregnancy. ALP levels in serum are abnormally high in biliary obstruction. Slight to moderate increase is seen in parenchymal liver diseases such as in hepatitis and cirrhosis and in metastatic liver disease.  Its normal serum level is 20-100 U/L.

Principle
The substrate, p- nitrophenyl phosphate (PNPP) is hydrolysed by ALP  to p- nitrophenol (PNP)(colourless) and phosphoric acid. PNPP is colorless in acid or alkaline medium while PNP is yellow in the alkaline medium and colourless in  acid medium and the concentration is determined by measuring the absorbance at 405 nm. 

     ALP

P-nitrophenyl phosphate + H₂O  --------------> P-nitrophenol + H₃PO₄ Colourless                                                                        Yellow   

Increased alkaline phosphatase activity  may be related to hepatobiliary and bone disease. Very high alkaline phosphatase activity in serum is seen in patient with bone cancer and marked increased also occur in obstructive jaundice and biliary cirrhosis. Modetrate elevations have been noted in case of Hodgkin’s disease, congestive heart   failure, infective hepatitis and abdominal problems.

 2) Bile pigments:
Bilirubin or hematoidin is the yellow breakdown product of normalheme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases. It is responsible for the yellow color of brusis, urine and the yellow discoloration injundice.
Bilirubin in serum would only react with diazo reagent in the presence of alcohol, after the proteins had been removed by precipitation. Normally 0.25mg/dl of conjugated bilirubin is present in the blood of an adult. Bilirubin rises in disease of hepatocytes, obstruction to biliary excretion into duodenum, in haemolysis, and defects of hepatic uptake and conjugation of bilirubin pigment such as Gilbert’s disease³⁴ .Estimation of bilirubin is one of the better liver function tests because the liver must take bilirubin away from the albumin to which it is bound in the circulation, conjugate it and excrete it into the bile-a truly complex series of reaction.        

Estimation of serum Total Bilirubin (TB) ³⁵.
The serum bilirubin level is one of the best tests of liver function.  Bilirubin is the metabolic product of the breakdown of heme derived from senescent red blood cells.  Each day about 7.5g of hemoglobin is catabolized with the corresponding production of 250 mg bilirubin.
Normally, 0.25 mg/dl of conjugated bilirubin is present in the blood of an adult.  Bilirubin level rises in diseases of hepatocytes, obstruction to biliary excretion into duodenum, in hemolysis and defects of hepatic uptake and conjugation of bilirubin treatment such as Gilbert’s disease.

Principle:
Bilirubin reacts with diazotized sulphanilic acid to form an azo compound, the color of which is measured at 546 nm (536-560 nm) and is proportional to the concentration of bilirubin.  The stability of final color of reaction of mixture is 10 minutes for total bilirubin and 5 minutes for direct bilirubin.

1.5.    Hepatoactive medicaments:
The literature review reveals that a large number of drugs of plant origin are endowed with hepatoprotective claims either directly or indirectly. In recent years, the usage of herbal drugs for the treatment of liver diseases has increased all over the world³⁶.The herbal drugs are believed to be harmless and free from serious adverse reactions, as they are obtained from nature  and are easily available. Also, the limited therapeutic options and disappointing therapeutic success of modern medicine including herbal preparations³⁷ .

In recent years many researchers have examined the effects of plants used traditionally by many folklore remedies from plant origin have long been used for the treatment of liver diseases  ³⁸indigenous healers and herbalists to support liver function and treat diseases of the liver. In most cases, research has confirmed traditional experience and wisdom by discovering the mechanisms and mode of action of these plants as well as reaffirming the therapeutic effectiveness of certain plants or plant extracts in clinical studies. Several hundred plants have been examined for use in a wide variety of liver disorders. Just a handful has been fairly well researched ³⁹

There are about 600 commercial herbal formulations, which are claimed to have hepatoprotective activity and many of them are being sold in market all over the world. In India, about 40 patented polyherbal formulations representing a variety of combinations of 93 herbs from 44 families are available⁴⁰. It has been reported that 160 phytoconstituents from 101 plants possess hepatoprotective activity⁴¹ . Liver protective herbal drugs contain a variety of chemical constituents like phenols, coumarins, lignans, essential oil, monoterpenes, carotenoids, glycosides, flavonoids, organic acids, lipids, alkaloids and xanthone  derivatives⁴⁰. Studies carried out in China and Japan resulted in the isolation of a hepatoprotective lignan, gomishin from the fruits of Chinese medicinal plant Schizandra chinensis. Gomishin is used for the treatment of chronic hepatitis. Studies carried out at Tropical Botanic Garden and Research Institute (TBGRI) have shown that Trichopus zeylanicus,Phyllanthus maderaspatensis and P. kozhikodianus are extremely active against paracetamol-induced liver damage in rats ^42,43,44. A recent report indicates that fumaric acid obtained from Sida cordifolia has significant anti-hepatotoxic activity in rat⁴⁵. Ursolic acid which occurs in many plants also showed promising hepatoprotection against paracetamol and CCl₄  induced liver damage in rats^46,47 .Some of the reported  constituents  with pharmacologically/therapeutically proved claims may be enlisted as silymarin, (+)- catechin, saikosaponins, curcumin, glycyrrhizin, picroside I and II gomisin etc⁴⁸ , acetyl bergenin ⁴⁹ and kolaviron⁵⁰ . Most commonly used plants in herbal formulations in India and scientifically validated in experimental animals are Andrographis paniculat)⁵¹, Boerhaavia diffusa, Eclipta alba, Picrorrhiza kurroa⁵² , Cichorium intybus, Tinospora cordifolia⁵³ .

Some of the polyherbal formulations are verified for their hepatoprotective action against chemical induced liver damage in experimental animals^54,55,56 : Liv.52^40,57, Liv.42, Liver cure, Tefroli ^51,58, Livol , Hepatomed⁵⁹ , Jigrine⁴⁰ , Stimuliv⁴⁴ , Koflet⁴⁰  and Icterine⁶⁰ .

Antioxidants can protect experimental animals and humans from oxidant mediated liver damages. This effect can be seen even in certain common vitamins, spices and vegetables (e.g. Vitamin-E and turmeric).Efficacy of the traditional and new herbal products should be tested by standard experimental methods. Also, there should be adequate data from in vivo and in vitro studies to validate the therapeutic potential claimed⁶¹.

Several plants have been reported  to have hepatoprotective acvity among those, a few plants tested against different experimental models  are listed  in below table.

2 . LIST OF HEPATOPROTECTIVE ACTIVITY HAVING MEDICINAL  

PLANTS:

BOTANICAL NAME	FAMILY	PLANT PARTS USED	SCREENING METHODS	REFERENCES
Acacia catechu	Leguminosae	Powdered pale catechu	Carbontetra chloride induced	62
Acacia confuse	Leguminosae	Bark	Carbon tetra chloride	63
Aegle marmelos Correa	Rutaceae	Leaves	Paracetamol Induced	64
Aerva lanata	Amaranthaceae	Coarce powder Plant	Paracetamol Induced	65
Alchornea cordifolia	Euphorbiaceae	Leaves	Paracetamol Induced	66
Alocasia indica Linn	Araceae	Leaves	Paracetamol Induced	67
Aloe barbadensis	Liliaceae	Dried aerial parts	Carbontetra chloride	68
Amaranthus spinosus	Amaranthaceae	Whole plant	Carbontetra chloride	69
Amaranthus caudatus Linn	Amaranthaceae	Whole plant	Carbontetrachloride Induced	70
Anisochilus carnosus Linn	Lamiaceae	Stems	Carbontetrachloride Induced	71
Apium graveolens	Apiaceae	Seeds	Paracetamol and thioacetamide	72
Arachiodes exilis	Dryppteridaceae	Rhizomes	Carbontetra chloride	73
Argemone mexicana	Solanaceae	Plant material	Carbontetra chloride	74
Asparagus racemosus Linn	Asparagaceae	Roots	Paracetamol induced	75
Azadirachta indica	Meliaceae	Leaf	Paracetamol Induced	76
Azitetracantha	Salvadoraceae	Leaves	Paracetamol induced	77
Baliospermum montanum	Euphorbiaceae	Roots	Paracetamol induced	78
Boerhaavia diffusa	Nyctaginaceae	Roots	Thioacetamide	79
Bupleurum kaoi	Umbelliferar	Dried roots	Carbontetra chloride	80
Byrsocarpus coccineus	Connaraceae	Leaf	Carbontetra chloride	81
Bixa orellana	Bixxaceae	Plant material	Carbontetra chloride	82
Cajanus cajan Linn	Leguminosae	Pigeon pea leaf	D-galactosamine	83
Cajanus scarabaeoide	Fabaeceae	Whole plant	Paracetamol induced	84
Carissa carindas Linn	Apocyanaceae	Root	Carbontetrachloride Induced	85
Carum copticum	Apiaceae	Seed	Carbontetra chloride,paracetamol	86
Calotropis procera	Asclepediaceae	Root bark	Carbontetrachloride Induced	87
Cassia  fistula	Leguminosae	Leaf	Carbontetrachloride Induced	88
Cassia tora	Caesalpiniaceae	Leaves	Carbontetra chloride	89
Cassia Occidentalis	Caesalpiniaceae	Leaves	Paracetamol and Ethyl alcoho	90
Chamomile capitula	Asteraceae	Fresh natural mature capitula	Paracetamol	91
Clerodendrum inerme	Verbenaceae	Leaves	Carbontetra chloride	92
Clitoria ternatea Linn	Fabaceae	Leaves	Paracetamol induced	93
Cleome viscose Linn	Capparidaceae	Leaf powder	Carbon tetra chloride	94
Cochlospermum planchoni	Coclospermaae	Rhizomes	Carbontetra chloride	95
Cichorium intybus	Asteraceae	Leaves	Thioacetamide	96
Cordia Macleodii	Boraginaceae	Leaves	Carbontetra chloride	97
Cuscuta chinensis	Convolvulaceae	Seeds	Acetaminophen	98
Decalepis hamiltonii	Asclepiadaceae	Roots	Carbontetra chloride	99
Elephrantopus scaber Linn	Asteraceae	Whole plant	D-galactosamine and acetaminophen	100
Equisetum arvense	equisetaceae	Aerial parts	Carbontetra chloride Induced	101
Embelia ribes	myrsinaceae	Fruits	Paracetamol induced	102
Enicostemma axillare	Gentianaceae	Whole plant	D-galactosamine	103
Euphorbia fusiformis	Euphorbiaceae	Tubers	Rifampicin	104
Ficus religiosa Linn	Moraceae	Stem bark	Paracetamol induced	105
Fructus schisandrae	Magnoliaceae	Dried fructus	Carbontetra chloride Induced	106
Fumaria indica	Papaveraceae	Whole plant	D-galactosamine	107
Ganoderma lucidum	Polyporaceae	Winter mushrooms	D-galactosamine	108
Ginkgo biloba	Ginkgoaceae	Dried extract	Carbontetra chloride Induced	109
Glyrrhiza glabra	Fabaceae	Root powder	Carbontetra chloride Induced	110
Gracinia indica Linn	Clusiaceae	Fruit rind	Carbontetrachloride Induced	111
Gmelina asiatica Linn	Verbenaceae	Aerial parts	Carbontetrachloride Induced	112
Gundelia tourenfortii	Asteraceae	Fresh edible stalk	Carbontetra chloride Induced	113
Halenia elliptica	Gentianaceae	Whole plant	Carbontetra chloride Induced	114
Hibiscus Sabdariffa	Malvaceae	Leaves	Paracetamol induced	115
Hibiscus esculentus	Malvaceae	Roots	Carbontetra chloride Induced	116
Hypericum japonicum	Clusiaceae	Whole plant	Carbontetra chloride Induced	117
Hygrophila auriculata	Acanthaceae	Root	Carbontetra chloride Induced	118
Hyptis suaveolens Linn	laminaceae	leaves	Acetaminophen induced	119
Hoslundia opposite	Lamiaceae	Stem	Carbontetra chloride And paracetamol Induced	120
Juncus subulatus	Juncaceae	Powdered tubers	Paracetamol  induced	121
Kalanchoe  pinnata	Crassulaceae	Leaves	Carbontetra chloride Induced	122
Lawsonia alba	Lythraceae	Whole plant	Carbon tetrachloride	123
Lactuca indica	Compositae	Aerial parts	Carbontetra chloride Induced	124
Luffa echinata	Curcubitaceae	Fruits	Carbontetra chloride Induced	125
Laggera  pterodonta	Asteraceae	Whole herb	Carbontetra chloride And  D-galactosamine Induced	126
Mallotus japonicas	Euphorbiaceae	Cortex	Carbontetra chloride Induced	127
Mamoridca subangulata	Cucurbitaceae	Leaf	Paracetamol  induced	128
Melia azhadirecta Linn	Piperaceae	Leaves	Carbontetrachloride, silymarin induced	129
Morinda citrifolia Linn	Rubiaceae	Fruit	Streptozotocin induced	130
Myoporum lactum Linn	myoporaceae	Leaves	Carbontetrachloride Induced	131
Myrtus communis Linn	Myrtaceae	Leaves	Paracetamol induced	132
Nelumbo nucifera	Nelumbonaceae	Leaves	Carbontetrachloride Induced	133
Nigella sativa	Ranunculaceae	Seeds	Tert –butyl hydroperoxide	134
Ocimum sanctum	Lamiaceae	Leaf	Paracetamol induced	135
Orthosiphan stamineus	Lamiaceae	Leaves	Acetaminophen	136
Phyllanthus amarus schum	Euphorbiaceae	Aerial part	Ehanol	137
Phyllanthus amarus	Euphorbiaceae	Whole plant except root	Aflatoxin b1 induced liver damage	138
Physalis minima	Solanaceae	Plant material	Carbontetra chloride	139
Phyllanthus niruri	Euphorbiaceae	Leaves and fruits	Carbontetrachloride Induced	140
Phyllanthus polyphullus	Euphorbiaceae	Leaves	Acetaminophen	141
Picrorhiza kurrooa	Scrophulariaceae	Root and rhizomes	Alcohol –carbon tetra chloride	142
Picrorrhiza rhizome	Scrophulariaceae	Dried underground stem	Poloxamer(PX)-407	143
Piper chaba	Piperaceae	Fruit	D-galactosamine	144
Piper longum	Piperaceae	Fruits and roots	Carbontetra chloride	145
Pittosporum neelgherrense	Pittospoaceae	Stem bark	Carbontetra chloride,  D-galactosamine and acetaminophen Induced	146
Plantago major	Plantaginaceae	Seeds	Carbontetra chloride	147
Pterocarpus marsupium	Papilionaceae	Stem bark	Carbontetra chloride	148
Ptrospermum acerifolium	Sterculiaceae	Leaves	Carbontetra chloride	149
Ricinus communis	Euphorbiaceae	Leaves	Carbon tetrachloride	150
Rubia cordifolia	Rubiaceae	Roots	Carbontetra chloride	151
Sarcostemma brevistigma	Asclepiadaceae	Stem	Carbontetra chloride	152
Saururus chinensis	Sauruaceae	Whole plant	Carbontetra chloride	153
Scoparia dulcis	Scrophulariaceae	Whole plant	Carbontetra chloride	154
Schouwia theebica	Arecaceae	Aerial part	Carbontetra chloride	155
Solanum nigram Linn	Solsnaceae	Fruits	Carbontetrachloride Induced	156
Tecomella undulate	Bignoniaceae	Stem bark	Thioacetamide	157
Tephrosia purpurea Linn	Fabaceae	Aerial parts	Thioacetamide	158
Thunbergia laurifolia	Acanthaceae	Leaves	Ethanol	159
Tridax procumbens	Asteraceae	Leaves	Carbontetrachloride Induced	160
Tylophora indica	Asclepiadaceae	Leaf  powder	Ethanol	161
Vitex trifolia	Verbenaceae	Leaves	Carbontetrachloride Induced	162
Vitis vinifera	Vitaceae	Leaves	Carbontetrachloride Induced	163

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