A Review on Hepatoprotective herbs for treatment of various liver Disorders

 

Tarasankar Maity1*,Ayaz  Ahmad1, Nilanjan Pahari2, Subarna Ganguli2

1Department of Pharmaceutical science, NIMS University, Shobha Nagar, Delhi Highway, Jaipur - 303121, Rajasthan, India.

2Department of Pharmacy, Calcutta Institute of Pharmaceutical Technology and AHS. Uluberia, Howrah-711316, West Bengal, India

*Corresponding Author E-mail: tarasankar8@gmail.com

 

ABSTRACT:

The liver plays a central role in transforming and clearing chemicals. Liver has one of the highest value of importance for the systemic detoxification and deposition of endogenous and exogenous substances. Liver diseases are considered to be serious health disorders.  Liver dysfunction that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. Drug-induced liver injury (DILI) possesses a major clinical problem. DILI has become the leading cause of acute liver failure and transplantation in Western countries. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure the organ. Other chemical agents, such as those used in laboratories (Thioacetamide, alcohol etc) and industries, natural chemicals (eg. microcystins)  are  induce hepatotoxicity. Modern medicines have little to offer for alleviation of hepatic diseases also they lead further damage to the liver. Hence plant based preparations which are employed for their treatment of liver disorders. Therefore, many folk remedies from plant origin are tested for its potential antioxidant and hepatoprotective liver damage in experimental animal model. Therefore the present review is aimed at compiling data based on pharmacologically active phytochemicals from medicinal plants that have been investigated in various hepatotoxicity animals  models.

 

KEYWORDS: Hepatotoxicity, microcystins, thioacetamide, antioxidant, phytochemicals.

 


INTRODUCTION:

Liver is the key organ, which plays a vital role in regulating various physiological processes in the body. It is involved in various vital functions, such as metabolism, secretion, storage supply of nutrients and energy. It has great capacity to detoxication and deposition of endogeneous substances1,2. The liver is expected not only to perform physiological functions but also to protect against the hazards associated with harmful drugs and chemicals3-5. It is widely exposed to xenobiotics, hepatotoxins, and chemotherapeutic agents that lead to impairment of its functions. Most common causes of liver diseases are viral infections, 6,7 drugs, 8,9 toxic chemicals, excess consumption of alcohol and autoimmune disorders. Most of the hepatotoxic chemicals damage liver cells due to lipid peroxidation as well as other oxidativedamages.10,11 Liver diseases are regarded as one of the serious health disorders.

 

Steroids, vaccines and antiviral drugs that are recommended as therapy for liver diseases. Those therapies have many adverse effects especially when administered for long periods of time. There is a worldwide trend for use of traditional system herbal medicines for the treatment of several liver diseases. Natural remedies from plant sources have been found as potential hepatoprotective agents with diverse chemical structures.  The Indian Traditional Medicine like Ayurveda, Siddha and Unani are based on the use of plant materials. Herbal drugs have lucrative importance and universal popularity in recent years due to of their safety, efficacy and cost effectiveness. In spite of the significant popularity of these medicinal systems, still there are some lacunas in treatment management for chronic liver diseases. The limiting factors are (i) lack of standardization of the herbal drugs;(ii) lack of randomized placebo controlled clinical trials (iii) lack of traditional toxicological evaluations and (iv) lack of identification of active chemical constituents.12

 

Hepatotherapeutic herbal medicines

The use of herbal medicine can be first started back to 2100 BC in ancient China at the time of Xia dynasty, and in India during the Vedic period. The first written books are timed to 600 BC with Charaka samhita of India.13There are more than 300 preparations in the Indian tradional systems of medicine for the treatment of jaundice and chronic liver diseases. In India more than 87 medicinal plants are used in different combinations as herbal drugs for liver diseases.14The development of herbal products clearly isolate and elucidate the active constituents as well as determine the mechanism based pharmacological activities. This would lead to quicker development of herbal medicinal sector. A semi-synthetic analogue of such compounds also be useful in pharmaceutical sector. Drugs discovered from herbs will give good therapeutic medicines with fewer side effects and lower cost. Significant number of herbals show promising activity for hepatotoxicity treatment like Aegle marmelos and Eclipta alba15 in alcohol induced hepatitis, Flacourtia indica16 to treat in ccl4 induced hepatitis also a number of herbal combinations from China and Japan that deserve testing in appropriate studies. The present review is based on reported research works on hepatoprotective phytochemicals from diverse medicinal plants that have been assayed in various hepatotoxicity models.     

 

Cissaampelos pareira17

The hepatoprotective effect of ethanolic root extract of Cissaampelos pareira on different dosages 100 mg/kg, 100 mg/kg and 100 mg/kg were assyed in ccl4 induced hepatotoxicity in rats. Liver functions were investigated by determination of SGOT, SGPT, ALP and bilirubin. In this model hepatotoxicity can be developed by inducing ccl4 with olive oil (2ml/kg body weight, I.P.). It has been observed that serum biochemical parameters like SGOT, SGPT, ALP and bilirubin levels are markedly elevated in hepatotoxic group. The treatment of ethanolic root extract of Cissaampelos pareira exhibited significant protective effect by lowering the serum biochemical parameters near to normal control rats. Histopathological studies also revealed that the administration of root extract with ccl4, exibited protective phenomenon on the liver.

 

Benincasa hispida18

The protective role of aqueous extract of pulps of Benincasa hispida was studied on diclofenac sodium- induced hepatotoxicity model in adult male albino rats. Hepatotoxicity in rats was produced by diclofenac sodium at a dose of 10 mg /ml/kg body weight for 28 days. After twenty eight days diclofenac sodium treatment group, the serum glutamate oxaloacetate Transaminase(SGOT),serum glutamate pyruvate transaminase(SGPT), AlkalinePhosphatase(ALP),superoxide dismutase(SOD) catalase(CAT) activities, reduced glutathione(GSH) and lipid  peroxidation (LPO) levels were estimated. There were a significant rise in SGOT, SGPT and ALP activities in the diclofenac sodium treated experimental animals as compared to the normal control group. The SGOT, SGPT and ALP activities were significantly decreased in Benincasa hispida treated group when compared to the diclofenac sodium treated experimental group. The hepatic oxidative stress parameters like LPO, GSH,CAT, SOD were also shown reverse values in Benincasa hispida treated animals as compared to diclofenac treated group. The findings indicated that the aqueous extract of pulps of Benincasa hispida provide a chief source of antioxidants that could offer potential protective effects against diclofenac induced hepatotoxicity.

 

Embelia tsjeriam-cottam19

The hepatotherapeutic role of both alcoholic and aquous fruit extracts of Embelia tsjeriam-cottam were investigated in isoniazid induced liver damage in rats. The groups treated with isoniazid(50gm/kg, for 30days) showed significantly elevated level of ALT, AST, billirubin and significantly decreased total protein content as compared to  normal control animals. The animals treated with aqueous, alcoholic extract showed significant reverse action in all the biochemical parameters. In vivo lipid peroxidation study reveals that rats of isoniazid treated group showed significant rise in malondialdehyde (MDA) when compared with rats of normal control group. The administration of alcoholic and aqueous extracts were significantly lowered the MDA level. There was a decrease in the level of GSH and the activities of SOD and CAT in isoniazid treated group when compared with normal control group. The GSH level and activities of SOD and CAT were significantly increased in alcoholic and aqueous extract treated group. Histopathological examination of liver from control group showed normal hepatic cells and natural hepatic morphology. The liver of the rats intoxicated with isoniazid there was vacuolation, sinus congestion, mild inflammation and centrilobular degeneration of hepatic cells with centrilobular necrosis. Both alcoholic extract and aqueous extract of Embelia tsjeriam-cottam were minimised the isoniazid induced liver toxicity.

 

Citrus reticulate20

The essential oil of Citrus reticulate was evaluated for hepatoprotective properties. Hepatotoxicity was produced by isoniazid (50gm/kg, p.o. for 30days). The essential oil (200mg/kg, p.o.) was administered every 24 hrs for thirty days, while standard group received Liv52. At the end of the study serum biochemical parameters were estimated. The group treated with isoniazid alone showed significantly sharp rise in ALT, AST, bilirubin and significantly decreased total protein content as compared to normal control (not treated with isoniazid) animals. The animals treated with essential oil of Citrus reticulata and Liv52 showed significantre reduction in all the biochemical parameters. So this above result suggested that the plant Citrus reticulate possesses strong hepatoprotective activity against isoniazid induced liver damage.

 

Phyllanthus polyphyllus21

Hepatoprotective and antioxidant activities of methanolic extract of Phyllanthus polyphyllus was evaluated against acetaminophen induced hepatotoxicity in rats. The plant extract showed a potent liver protective as well as antioxidant activity against acetaminophen produced hepatotoxicity  in rats.  Animals treated with acetaminophen (750 mg/kg p.o.) showed sharp rise in aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a remarkable reduction of total protein(TP), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione S-transferase (GST). Treatment of rats with different doses of plant extract (200 and 300 mg/kg,p.o.) significantly reversed serum marker enzymes and antioxidant levels to near normal rats when compared to acetaminophen treated rats. Histopathological changes of liver sample were compared with all groups. Histopathological reports showed that the Phyllanthus polyphyllus treated rats provide a sign of protection against acetaminophen-induced hepatotoxicity in rats. Above results indicated that the herbal plant Phyllanthus polyphyllus having potent hepatoprotective and antioxidant properties.

 

Bombax ceiba L.22

Bombax ceiba (Bombacaceae) is a potent medicinal plant of tropical and subtropical India. Its therapeutic usage has been reported in the traditional systems of medicine such as Ayurveda, Siddha and Unani. Liver protective activity of methanolic extract of flowers of Bombax ceiba L. was assayed against Isoniazid and Rifampicin produced hepatotoxicity in Wistar strain male albino rats. Hepatotoxicity in rats was produced by combination of two anti-tubercular drugs Isoniazid and Rifampicin for 10 and 21 days through intraperitoneal route in rats. Three graded dose of Bombax ceiba L. (150, 300 and 450 mg/kg i.p.) were administered to study the hepatoprotective activity. It has been observed that there were a significant rise in AST, ALT, ALP,  Total Bilirubin and markedly decreased in total protein level for Isoniazid and Rifampicin treated rats when compared to normal control rats. Different dosage administration of Bombax ceiba L. significantly altered the serum enzymes levels. This plant markedly lowered the level of TBARS and elevated the level of GSH at all doses as compared to normal control. Histology of the liver section of the animals treated with Bombax ceiba L.  protected the liver damage caused by isoniazid and rifampicin. Except hepatotoxicity this plant also widely used in Inflammation23, hypertension, antiangiogenic and antioxidant activities.24

 

Calotropis gigantean25

The ethanolic flower extract of Calotropis gigantean was investigated for hepatoprotective properties. Liver damage was produced by ethanol. The elevated levels of AST, ALT, ALP, LPO, and very lowered level of vitamin C were indicated that severe liver damage occurred in alcohol treated animals. Pretreatment with 250 and 500 mg/kg body weight of Calotropis gigantean extract significantly decreased the levels of enzyme markers, lipid peroxidation and markedly increased serum vitamin C level. The pharmacological effect of the extract may be due to its antioxidant ability to inhibit lipid peroxidation as well as prevent the depletion of vitamins C.

 

Tecomella undulate26

The methanolic extract of folk herbal plant, Tecomella undulate leaves was studied against alcohol and paracetamol induced liver damage of albino rats. Levels of serum marker enzymes like AST, ALT, ALP , GGT (gamma glutamyl transpeptidase) and total bilirubin in serum alongwith the activities of LPO (lipid peroxidation), SOD (superoxide dismutase), CAT (catalase), GSH (reduced glutathione) and GPx (glutathione peroxidase) in liver from treated rats were assayed accordingly. The histopathological changes of liver sections were also compared with the respective controls. Serum marker enzymes hepatic oxidative stress parameters (SOD, CAT, GSH and GPx) were significantly (P<0.001) increased and LPO markedly reduced in 30% alcohol and paracetamol induced rats. Oral treatment with Tecomella undulate (100 mg/kg, 200mg/kg, b. wt / day) altered to all the serum and liver parameters in 30% alcohol and paracetamol treated rats. The biochemical results were also compared with the standard drug silymarin (25 mg/kg b. wt/day). These findings indicate the hepatoprotection offered by Tecomella undulate leaves against liver damage might be due to the presence of flavonoids, quinones and other antioxidents.

 

Pisonia aculeate27

 The effect of methanolic extract of leaves of Pisonia aculea showed a significant hepatoprotection and antioxidant activity against Rifampicin and Isoniazid induced hepatotoxicity as judged from the serum marker enzymes and antioxidant levels in liver tissues. Rifampicin and Isoniazid induced animals showed  a significant rise in aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a reduction of total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), reduced glutathione (GSH), Glutathione reductase (GR), Vitamin C and E. Treatment of rats with different doses of methanolic extract of leaves of Pisonia aculea  (250 and 500 mg/kg) significantly (P<0.001) reversed the levels of serum marker enzymes and antioxidant enzymes to near normal control rats when compared to Rifampicin and Isoniazid induced hepatotoxicity rats. This extract also altered the drug metabolizing enzymes such as NADPH Cytochrome C reductase, Cytochrome P450, and glutathione S transferase. In this stydy hepatoprotective ability of the extract at dose of 500 mg/kg was well comparable to the standard drug, silymarin (50 mg/kg, p.o.). Histopathological changes of liver sample were compared with respective control. Results indicate the hepatoprotective and antioxidant properties of Pisonia aculeata against rifampicin and isoniazid -induced hepatotoxicity in rats. This medicinal plant also effective against ccl4 induced hepatotoxicity model.28The findings indicated that the methanolic extract of leaves of Pisonia aculea retain a chief source of bioactive constituents that could offer protective effects against rifampicin and isoniazid induced hepatotoxicity.

 

Pyrenacantha staudtii29

The protective effect of ethanol extract of Pyrenacantha staudtii leaves on carbon tetrachloride (CCl4) induced hepatotoxicity in rats was investigated in experimental model. Sixteen male wistar rats of 100-170g body weight equally divided into four groups, designated as group I, II, III and IV. Groups II, III and IV were injected intraperitoneally with 5ml/kg body weight of CCl4 where as normal control was injected with 5ml/kg body weight corn oil. After 48hrs, groups III and IV were administered with ethanol extract of Pyrenacantha staudtii (750mg/kg and 1500mg/kg body weight) respectively. Then rats were sacrificed after 5 days. Based on the experimental study showed that both ethanolic extract (750mg/kg and 1500mg/kg body weight) significantly lowered the levels of liver enzymes- alanine aminotransferase (ALT) and Aspartate aminotransferase (AST), which were markedly elevated in ccl4 treated rats. CCl4 induced animals increased in total and conjugated bilirubin as compared to normal rats. But both ethanolic extracts were also significantly altered the bilirubin levels in dose dependent manner. The extract of Pyrenacantha staudtii leaves has hepatoprotective effect against CCl4 induced hepatotoxicity toxicity and damage due to presence of flavonoids and other bioactive chemical constituents.

 

Orthosiphon stamineus30

Orthosiphon stamineus is an important herbal plant traditionally used in Malaysia for treatment of various types of liver disorders. The ethanol extracts were used to study the hepatotherapeutic effects in a thioacetamide-induced hepatotoxicity model in Sprague Dawley rats. Forty rats were taken for experimental model. Five groups of adult rats(each group contain eight animals) were arranged as follows: Group 1 (normal control group), Group 2 Thioacetamide as positive control (hepatotoxic group), Group 3 Silymarin as a well-known standard drug (hepatoprotective group), and Groups 4 and 5 as high and low dose (treatment groups). After 2 month treatment, all rats were sacrificed. The hepatotoxic group showed a significant increase in serum liver biochemical parameters (ALT, AST, ALP, and Bilirubin) and the level of liver Malondialdehyde (MDA), accompanied by a significant decrease in the level of total protein and Albumin, when compared with that of the normal group animals. The high-dose treatment with ethanol extracts of  Orthosiphon stamineus  (200mg/kg) significantly altered the elevated liver function enzymes near to normal value.Histopathological studies also support the sign of protection. These experimental reports revealed that the Orthosiphon stamineus is a vital ayurvedic plant which exerted hepatoprotection effect against thioacetamide-induced hepatotoxicity in rats.

 

Chenopodium album Linn31

The present review describes hepatoprotective activities of dried whole plant of Chenopodium album Linn against paracetamol induced liver damage. Liver injury was produced by applying 2.5ml/kg oral route of pracetamol in equal proportion with dimethysulfoxide (DMSO). Acetone and Methanol extract at lower and higher dose (200 and 400 mg/kg), offered significant (P<0.001) hepatoprotective action by lowering the levels of serum marker enzymes like serum glutamate oxaloacetate (SGOT), serum glutamate transaminase (SGPT), serum alkaline phosphatase (ALP), serum acid phosphatase (ACP) and serum bilirubin as compared to hepatotoxic group.  With the administration of methanol and acetone extract of Chenopodium album Linn. Levels of oxidative stress parameters were restored to normal value.  Histopathological studies further confirmed the hepatoprotection by those extracts when compared with Paracetamol treated control groups. The pharmacological investigations were compared with silymarin (100mg/kg; oral) as the standard drug.

 

Ziziphus mauritiana32

The protective effects of aqueous extract of Ziziphus mauritiana leaf on alcohol induced hepatotoxicity in rats was investigated. Thirty six male Wistar albino rats weighing between 100-120 g were equally distributed into six groups of six rats respectively and treated for six weeks. Hepatotoxicity can be achieved by Chronic administration of alcohol at (40% v/v, 1ml/100g), for 6 weeks showed a significant (p<0.05) rise in levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) reduced levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase as compared to normal control rats. Whereas pretreatment of rats different doses 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin significantly (p<0.05) restored the levels of ALT, AST, ALP, and TB near to normal value. As well as the administration of Ziziphus mauritiana  markedly elevated those following antioxidant parameters like catalase,glutathione peroxidase, glutathione reductase and superoxide dismutase when compared to group treated with  alcohol only. Histopathology of rat liver treated with alcohol only showed in cell necrosis,fatty degeneration, etc which indicated severe liver damaged. Treatment with the aqueous extract of Ziziphus mauritiana or silymarin prevented the morphological changes as well as cell necrosis that are associated with chronic alcohol consumption. The protective activity of the plant Ziziphus mauritiana may be due to the presence of antioxidant constituent i.e tannins, saponins and phenolic compounds etc.

 

Aerva lanata33

The liver protective ability of hydro-alcholic extract of Aerva lanata was assayed on Paracetamol induced hepatotoxicity in rats. Liver damage can be achieved by paracetamol at the dose of 3gm/kg. The hepatic enzymes like as ALT, AST, ALP and bilirubin in serum were significantly (P <0.001) increased in paracetamol treated animals when compared to normal control. When treated with hydro-alcholic extract of Avera lanata, serum biochemical parameters were significantly (P < 0.01) altered the levels of AST, ALP and bilirubin P < 0.01) and ALT (P<0.001) when compared to paracetamol  treated animals. In this study hepatoprotective drug Silymarin (25 mg/kg) was used as standard also showed significant reduction in AST, ALT, ALP and bilirubin (P<0.001) levels when compared to paracetamol treated rats. From the above review it can be regarded as the medicinal plant Aerva lanata proved to be a hepatoprotective  herbal drug.

 

Allium cepa34

Cadmium(Cd) is a toxic heavy metal frequently used in various industries. Cadmium metal related with various tissue damage.35,36 Liver is the vital organs of the body system, helps to detoxify toxic substances such as Cd by generating detoxifying enzymes.37 The  extracts of Allium cepa was used to study the hepatotherapeutic effects in acadmium sulphate induced hepatotoxicity model in rats.  Administration of Cd sulphate (1.5mg/100kgBW/day) caused reduction in body weight gain, hepatic SOD activity, total serum protein and markedly increased in hepatic malondialdehyde (MDA) level, and serum alkaline aminotransferase (ALT), and alkaline aspartate aminotransferase (AST) activities. Treatment with extracts of Allium cepa  (1.0mml /100kgBW/ day) significantly restored the serum marker enzymes and oxidative stress parameters in normal level. So this plant shows hepatoprotection against Cd induced liver damage and it is proved to be a herbal remedies for liver ailment.

 

DISCUSSION

India is a diversity source of herbal plants and is one of the richest countries in the world with regard to genetic resources for medicinal plants. Increased awareness regarding herbal drugs is due to current widespread belief that ‘‘green medicine’’ is safe, more accessible and more affordable than costly synthetic drugs, many of which have adverse side effects.38 Liver disorder are some of the mortal disease in the world today. They propound a serious challenge to international public health. Modern medicines have little to offer for mitigation of liver complications. Now days plant bassed herbal preparations are very popular and those medicines are widely used globally due to their therapeutic efficacy. Those plant based drugs are contain many bioactive chemical constituents i.e flavonoids, tannins, polyphenolic copounds etc. responsible for antioxidant property. But there is not much drug available for the treatment of liver disorders.39That’s why many folk remedies are assayed to evaluate its hepatoprotective activity on different experimental animal models. Carbon tetrachloride induced hepatotoxicity model,40 Paracetamol induced hepatotoxicity model,41 Diclofenac induced hepatotoxicity model,42 Thioacetamide induced hepatotoxicity model,43cadmium induced hepatotoxicity model, Alcohol induced hepatotoxicity model,44 isoniazid induced induced hepatotoxicity model 45etc are widely used for the investigation  of the hepatoprotective efficacy of synthetic drugs as well as herbal drugs. Inspite of popularity of herbal drugs, there were some lacuna regarding herbal drug research. Many reports on adverse drug effects contradict the popular view that herbal drugs are natural and are harmless. A survey by the National Poison Information Service for the years 1991–1995 documented 785 cases of possible as well as confirmed adverse reactions associated with herbal drugs. Hence, safety studies are very essential to cultivate sufficient data that may help for future development of herbal drugs.46-50

 

CONCLUSION

Chronic hepatic disorders are regarded as burning health trouble in worldwide, associated with hepatitis, alcoholic liver diseases, fatty liver diseases, liver cancer etc. Use of modern synthetic medicines may cause diverse adverse drug reactions as well as those are  high cost. Hence treating liver complications with plant based bioactive constituents are more popular with low cost. In this review article has reported many hepatoprotective medicinal plants from India and abroad. It may be useful for the pharmaceutical professionals, health professionals and research scientists to grow an interest for  working in the field of phytomedicine to develop herbal medicine which will be  cured different kinds of liver disorders in man and animals.  

 

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Received on 05.04.2012          Modified on 28.04.2012

Accepted on 12.05.2012         © RJPT All right reserved

Research J. Pharm. and Tech. 5(5): May2012; Page 602-607