Hepatotoxicity and the present herbal hepatoprotective scenario

Priyankar Dey, Manas Ranjan Saha, Arnab Sen


Most of the metabolic and physiological processes of our body as well as the detoxification of various drugs and xenobiotic
chemicals occur in the liver. During this detoxification process, the reactive chemical intermediates damage the liver severely. There are several commercially available drugs, consumption of which results in idiosyncratic drug reaction mediated hepatotoxicity. Drug induced hepatotoxicity is a burning problem in this regard and several drugs are withdrawn from the market due to their hepatotoxic nature. Today, worldwide search of non‑hepatotoxic drugs, especially potent hepatoprotective drugs have led towards the screening of numerous herbal products. Pharmaceutical companies and scientific communities have started to consider the therapeutic efficiency of the plant‑based hepatoprotective remedies. Different herbs are mentioned in various ethnopharmacological practices possessing hepatoprotective capacities and around the globe, such herbs are still used by people to cure certain liver diseases. Therefore, we have documented the various aspects of hepatotoxicity and an overview on the current scenario of the hepatoprotective herbal remedies.
Key words: Ayurveda, drug induced hepatotoxicity, ethnopharmacology, hepatoprotective, hepatotoxicity, herbal, idiosyncratic
drug reactions, liver

Full Text:



Liver transplant. Available from: http://www.nhs.uk/conditions/

Liver‑transplant/Pages/Introduction.aspx [Last accessed date

Jan 3].

Lynch T, Price A. The effect of cytochrome P450 metabolism on

drug response, interactions and adverse effects. Am Fam Physician


Blazka ME, Wilmer JL, Holladay SD, Wilson RE, Luster MI. Role

of pro‑inflammatory cytokines in acetaminophen hepatotoxicity.

Toxicol Appl Pharmacol 1995;133:43‑52.

Navarro VJ, Senior JR. Drug‑related hepatotoxicity. N Engl J Med


Kshirsagar AD, Mohite R, Aggrawal AS, Suralkar UR.

Hepatoprotective medicinal plants of ayurveda: A review. Asian

J Pharm Clin Res 2011;4:1‑8.

Sharma YK, Singh H, Mehera BL. Hepatoprotective effect of few

herbs in patients receiving antituberculus treatment. Indian J Tradit

Knowl 2004;3:391‑6.

Thyagarajan SP. Changing therapy: Treatment of viral hepatitis

in modern and alternative medicine systems. IAPJ Pract Pediatr


Guidelines for the Appropriate use of Herbal Medicines: The

role of herbal medicines. Available from: http://apps.who.int/

medicinedocs/en/d/Jh2945e/[Last accessed date 2013 May 12].

Malaysia’s national policy on biological diversity. Available from:



c‑8d0a‑afa7076c3663 [Last accessed date 2013 May 16].

Medicinal plants and extracts. Available from: http://www.

intracen.org/trade‑support/medicinal‑plants/[Last accessed date

Jan 27].

Singh VK, George CX, Gupta KP, Gupta BM. Antiviral activity of

plant extract Liv 52 in mice experimentally infected with semliki

forest encephatitis virus. Sci Cult 1983;49:354‑5.

Pramyothin P, Chirdchupunsare H, Rungsipipat A,

Chaichantipyuth C. Hepatoprotective activity of Thunbergia

laurifolia Linn extract in rats treated with ethanol: In vitro and

in vivo studies. J Ethnopharmacol 2005;102:408‑11.

Singh A, Handa SS. Hepatoprotective activity of Apium graveolens

and Hygrophila auriculata against paracetamol and thioacetamide

intoxication in rats. J Ethnopharmacol 1995;49:119‑26.

Srivastava A, Shivanandappa T. Hepatoprotective effect of the root

extract of Decalepis hamiltonii against carbon tetrachloride‑induced

oxidative stress in rats. Food Chem 2010;118:411‑7.

Gujrati V, Patel N, Rao VN, Nandakumar K, Gouda TS,

Shalam MD. Hepatoprotective activity of alcoholic and aqueous

extracts of leaves of Tylophora Indica (Linn.) in rats. Indian J

Pharmacol 2007;39:43‑7.

Gupta AK, Misra N. Hepatoprotective activity of aqueous ethanolic

extract of Chamomile capitula in paracetamol intoxicated albino rats.

Am J Pharmcol Toxicol 2006;1:17‑20.

Amat N, Upur H, Blazekovic B. In vivo hepatoprotective

activity of the aqueous extract of Artemisia absinthium L. against

chemically and immunologically induced liver injuries in mice.

J Ethnopharmacol 2010;131:478‑84.

Hewawasam RP, Jayatilaka KA, Pathirana C, Mudduwa LK.

Hepatoprotective effect of Epaltes divaricata extract on carbon

tetrachloride induced hepatotoxicity in mice. Indian J Med Res


Zeashan H, Amresh G, Singh S, Rao CV. Hepatoprotective activity

of Amaranthus spinosus in experimental animals. Food Chem

Toxicol 2008;46:3417‑21.

Manoharan S, Jaswanth A, Sengottuvelu S, Nandhakumar J,

Duraisamy R, Karthikeyan D, et al. Hepatoprotective activity of

Aerva Lanata Linn against paracetamol induced hepatotoxicity in

rats. Res J Pharm Tech 2008;1:398‑400.

Ahmed B, Alam T, Varshney M, Khan SA. Hepatoprotective activity

of two plants belonging to the apiaceae and the euphorbiaceae

family. J Ethnopharmacol 2002;79:313‑6.

Singhal KG, Gupta GD. Hepatoprotective and antioxidant

activity of methanolic extract of flowers of Nerium oleander

against CCl4 induced liver injury in rats. Asian Pac J Trop Med


Rahiman F, Kumar R, Mani T, Niyas M, Kumar S, Phaneendra P,

et al. Hepatoprotective activity of Asparagus racemosus root on liver

damage caused by paracetamol in rats. Indian J Novel Drug Del


Kamat JP, Boloor KK, Devasagayam TP, Venkatachalam SR.

Antioxidant properties of Asparagus racemosus against damage

induced by G‑Radiation in rat liver mitochondria. J Ethnopharmacol


Olaleyea MT, Rocha BT. Acetaminophen‑induced liver damage in

mice: Effects of some medicinal plants on the oxidative defence

system. Exp Toxicol Pathol 2008;59:319‑27.

Ahsan MR, Islam KM, Bulbul IJ, Musaddik MA, Haque E.

Hepatoprotective activity of methanol extract of some medicinal

plants against carbon tetrachloride‑induced hepatotoxicity in rats.

Eur J Sci Res 2009;37:302‑10.

Aliyu R, Okoye ZS, Shier WT. The hepatoprotective cytochrome

p‑450 enzyme inhibitor isolated from the nigerian medicinal

plant Cochlospermumplanchonii is a zinc salt. J Ethnopharmacol


Jain A, Soni M, Deb L, Jain A, Roult AP, Gupta VB, et al. Antioxidant

and hepatoprotective activity of ethanolic and aqueous extracts of

Momordica dioica Roxb. leaves. J Ethnopharmacol 2008;115:61‑6.

Sathesh Kumar S, Ravi Kumar B, Krishna Mohan G.

Hepatoprotective effect of Trichosanthescucumerina var cucumerina

L. on carbon tetrachloride induced liver damage in rats.

J Ethnopharmacol 2009;123:347‑50.

Aghela N, Rashidib I, Mombeinia A. Hepatoprotective activity of

Capparis spinosa root bark against CCl4 induced hepatic damage

in mice. Iran J Pharm Res 2007;6:285‑29.

Zhou D, Ruan J, Cai Y, Xiong Z, Fu W, Wei A. Antiantioxidant

and hepatoprotective activity of ethanol extract of Arachniodes

exilis (Hance) Ching. J Ethnopharmacol 2010;129:232‑7.

Wadekar RR, Supale RS, Tewari KM, Patil KS, Jalalpure SS.

Screening of roots of Baliospermum montanum for hepatoprotective

activity against paracetamol induced liver damage in albino rats.

Int J Green Pharm 2010;2:220‑3.

Chandan BK, Saxena AK, Shukla S, Sharma N, Gupta DK,

Singh K, et al. Hepatoprotective activity of Woodfordia fruticosa

Kurz flowers against carbon tetrachloride induced hepatotoxicity.

J Ethnopharmacol 2008;119:218‑24.

Lim H, Kim H, Choi H, Oh S, Choi J. Hepatoprotective effects

of bergenin, a major constituent of Mallotus japonicus, on carbon

tetrachloride‑intoxicated rats. J Ethnopharmacol 2000;72:469‑74.

Harish R, Shivanandappa T. Antioxidant activity and

hepatoprotective potential of Phyllanthus niruri. Food Chem


Khatri A, Garg A, Agrawal SS. Evaluation of hepatoprotective

activity of aerial parts of Tephrosia purpurea L. And stem bark of

Tecomella undulate. J Ethnopharmacol 2009;122:1‑5.

Bhakta T, Mukherjee PK, Mukherjee K, Banerjee S, Mandal SC,

Tapan TK, et al. Evaluation of hepatoprotective activity of Cassia

fistula leaf extract. J Ethnopharmacol 1999;66:277‑82.

Chaudhari NB, Chittam KP, Patil VR. Hepatoprotective activity

of Cassia fistula seeds against paracetamol‑induced hepatic injury

in rats. Arch Pharm Sci Res 2009;1:218‑21.

Tung YT, Wu JH, Huang CC, Peng HC, Chen YL, Yang SC, et al.

Protective effect of Acacia confusa bark extract and its active

compound gallic acid against carbon tetrachloride‑induced chronic

liver injury in rats. Food Chem Toxicol 2009;47:1385‑92.

Orhana DD, Aslana M, Aktay G, Ergunc E, Yesiladaa E, Erguna F.

Evaluation of hepatoprotective effect of Gentiana olivieriherbs on

subacute administration and isolation of active principle. Life Sci


Huang B, Ban X, He J, Zeng H, Zhang P, Wang Y. Hepatoprotective

and antioxidant effects of the methanolic extract from Halenia

elliptica. J Ethnopharmacol. 2010;1131:276‑81.

Abdel‑Razik AF, Elshamy AS, Nassar MI, El‑Kousy SM, Hamdy H.

Chemical constituents and hepatoprotective activity of Juncus

subulatus. Rev Latinoam Quím 2009;37:70‑84.

Chin JH, Hussin AH, Ismai S. Anti‑hepatotoxicity effect of

Orthosiphon stamineus Benth against acetaminophen‑induced liver

injury in rats by enhancing hepatic GST activity. Pharmacogn Res


Akah PA, Odo CL. Hepatoprotective effect of the solvent fractions

of the stem of Hoslundia opposite Vahl (Lamiaceae) against carbon

tetrachloride and paracetamol induced liver damage in rats. Int J

Green Pharm 2010;4:54‑8.

Chattopadhyay RR, Sarkar SK, Ganguly S, Medda C, Basu TK.

Hepatoprotective activity of Ocimum sanctum leaf extract against

paracetamol induced hepatic damage in rats. Indian J Pharmacol


Chandan BK, Saxena AK, Shukla S, Sharma N, Gupta DK, Suri KA,

et al. Hepatoprotective potential of Aloe barbadensis Mill. against

carbon tetrachloride induced hepatotoxicity. J Ethnopharmacol


Sunilson JA, Jayaraj P, Mohan MS, Kumari AA, Varatharajan R.

Antioxidant and hepatoprotective effect of the roots of Hibiscus

esculentus Linn. Int J Green Pharm 2008;2:200‑3.

Chattopadhyay RR, Bandyopadhyay M. Possible mechanism of

hepatoprotective activity of Azadirachta indica leaf extract against

paracetamol‑induced hepatic damage in rats: Part III. Indian J

Pharmacol 2005;37:184‑5.

Tabassum N, Agrawal SS. Hepatoprotective activity of Emebelia

ribes against paracetamol induced acute hepatocellular damage

in mice. Exp Med 2003;10:43‑4.

Rawat KS, Mehrotra S, Tripathi SC, Shome U. Hepatoprotective

activity of Boerhaavia diffusa L. roots-a popular Indian

ethnomedicine. J Ethnopharmacol 1997;56:61‑6.

Bo H, Xiaoquan B, Jingsheng H, Jing T, Jun T, Youwei W.

Hepatoprotective and antioxidant activity of ethanolic extracts

of edible lotus (Nelumbo Nucifera Gaertn.) leaves. Food Chem


Matsuda H, Ninomiya K, Morikawa T, Yasuda D, Yamaguchi I,

Yoshikawa M. Hepatoprotective amide constituents from the fruit

of Piper chaba: Structural requirements, mode of action, and new

amides. Bioorg Med Chem 2009;17:7313‑23.

Patel JA, Shah US. Hepatoprotective activity of Piper longum.

Traditional milk extract on carbon tetrachloride induced liver

toxicity in wistar rats. Boletín Latinoamericano y del Caribe de

Plantas Medicinales y Aromáticas 2009;8:121‑9.

Shi Y, Sun J, He H, Guo H, Zhang S. Hepatoprotective effects of

Ganoderma lucidum peptides against D‑galactosamine‑induced

liver injury in Mice. J Ethnopharmacol 2008;117:415‑9.

Daba MH, Abdel‑Rahman MS. Hepatoprotective activity of

thymoquinone in isolated rat hepatocytes. Toxicol Lett 1998;95:23‑9.

Rao GM, Rao CV, Pushpangadan P, Shirwaikar A. Hepatoprotective

effects of rubiadin, a major constituent of Rubia cordifolia Linn.

J Ethnopharmacol 2006;103:484‑90.

Singh R, Rao HS. Hepatoprotective effect of the pulp/seed of Aegle

marmelos Correa e ×. Roxb. against carbon tetrachloride induced

liver damage in rats. Int J Green Pharm 2008;2:232‑4.

Ranawat LS, Bhatt J, Patel J. Hepatoprotective activity of ethanolic

extracts of bark of Zanthoxylum armatum DC in CCl4 induced

hepatic damage in rats. J Ethnopharmacol 2010;127:777‑80.

Kharpate S, Vadnerkar G, Jain D, Jain S. Evaluation of

hepatoprotective activity of ethanol extract of Ptrospermum

acerifloium Ster leaves. Indian J Pharm Sci 2007;69:850‑2.

Praveen TK, Dharmaraj S, Bajaj J, Dhanabal SP, Manimaran S,

Nanjan MJ, et al. Hepatoprotective activity of petroleum ether,

diethyl ether and methanol extract of Scoparia dulcis L. against

CCl4‑induced acute liver injury in mice. Indian J Pharmacol


Lee HS, Ahn HC, Ku SK. Hypolipidemic effect of water extracts

of Picrorrhiza rhizoma in PX‑407 induced hyperlipemic ICR

mouse model with hepatoprotective effects: A prevention study.

J Ethnopharmacol 2006;105:380‑6.

Wang L, Cheng D, Wang H, Di L, Zhou X, Xu T, et al. The

hepatoprotective and antifibrotic effects of Saururus chinensis

against carbon tetrachloride induced hepatic fibrosis in rats.

J Ethnopharmacol 2009;126:487‑91.

Arthika S, Shanthammal Y, Sheryl Igal1 N, Elankini P, Pramod

Reddy G, Gaidhani SN, et al. Hepatoprotective activity of the

ethanolic extract of Azima tetracantha against paracetamol‑induced

hepatotoxicity in wistar albino rats. J Adv Pharm Health Res


Wang BJ, Liu CT, Tseng CY, Wu CP, Yu ZR. Hepatoprotective

and antioxidant effects of Bupleurum kaoi Liu (Chao Et Chuang)

extract and its fractions fractionated using supercritical CO2 on

CCl4‑induced liver damage. Food Chem Toxicol 2004;42:609‑17.

Gopal N, Sengottuvelu S. Hepatoprotective activity of Clerodendrum

inerme against CCl4 induced hepatic injury in rats. Fitoterapia


Manjunatha BK, Vidya SM. Hepatoprotective activity of Vitex

trifolia against CCl4 induced hepatic damage. Indian J Pharm Sci


Orhan DD, Orhan N, Ergun E, Ergun F. Hepatoprotective effect of

Vitis vinifera L. leaves on carbon tetrachloride‑induced acute liver

damage in rats. J Ethnopharmacol 2007;112:145‑51.

Oliveira FA, Chaves MH, Almeida FR, Lima RC Jr, Silva RM,

Maia JL, et al. Protective effect of α‑ and β‑amyrin, a triterpene

mixture from Protium heptaphyllum (Aubl.) March. trunk wood

resin, against acetaminophen‑induced liver injury in mice.

J Ethnopharmacol 2005;98:103‑8.

Yoshikawa M, Xu F, Morikawa T, Ninomiya K, Matsuda H.

Anastatins A and B, new skeletal flavonoids with hepatoprotective

activities from the desert plant Anastatica hierochuntica. Bioorg Med

Chem Lett 2003;13:1045‑9.

Matsuda H, Morikawa T, Xu F, Ninomiya K, Yoshikawa M. New

isoflavones and pterocarpane with hepatoprotective activity from

the stems of Erycibe expansa. Planta Med 2004;70:1201‑9.

Amin H, Mingshi W, Hong YH, Decheng Z, Lee KH.

Hepatoprotective triterpenes from Sedum sarmentosum. Phytochem


Janbaz KH, Saeed SA, Gilani AH. Protective effect of rutin

on paracetamol and CCl4‑induced hepatotoxicity in rodents.

Fitoterapia 2002;73:557‑63.

Morita T, Jinno K, Kawagishi H, Arimoto Y, Suganuma H, Inakuma T,

et al. Hepatoprotective effect of myristin from nutmeg (Myristica

fragrans) on lipopolysaccharide/d‑galactosamine‑induced liver

injury. J Agric Food Chem 2003;51:1560‑5.

Lin CC, Lee HY, Chang CH, Namba T, Hattori, M. Evaluation

of the liver protective principles from the root of Cudrania

cochinchinensisvar. gerontogea. Phytother Res 2003;10:13‑7.

Song EK, Kim JH, Kim JS, Cho H, Nan JX, Soku DH, et al.

Hepatoprotective phenolic constituents of Rhodiola sachalinensison

tacrine‑induced cytotoxicity in Hep G2 cells. Phytother Res


Visen PK, Shukla B, Patnaik GK, Kaul S, Kapoor NK, Dhawan BN.

Hepatoprotective activity of picroliv, the active principle of

Picrorhiza kurrooa, on rat hepatocytes against paracetamol toxicity.

Drug Dev Res 1991;22:209‑19.

Hase K, Li J, Basnet P, Xiong Q, Takamura S, Namba T, et al.

Hepatoprotective principles of Swertia japonicaon D‑galactosamine/

lipopolysaccharide‑induced liver injury in mice. Chem Pharm Bull


Yoshikawa M, Ninomiya K, Shimoda H, Nishida N, Matsuda H.

Hepatoprotective and antioxidative properties of Salacia

reticulata: Preventive effects of phenolic constituents on

carbontetrachloride‑induced liver injury in mice. Biol Pharm Bull


Oh H, Kim JS, Song EK, Cho H, Kim DH, Park SE, et al.

Sesquiterpenes with hepatoprotective activity from Cnidium

monnierion tacrine‑induced cytotoxicity in Hep G2 cells. Planta

Med 2002;68:748‑9.

Park EJ, Zhao YZ, Kim YH, Lee JJ, Sohn DH. Acanthoic acid from

Acanthopanax koreanumprotects against liver injury induced by

tert‑butyl hydroperoxide or carbon tetrachloride in vitro and

in vivo. Planta Med 2004;70:321‑7.

Shim SB, Kim NJ, Kim DH. β‑Glucuronidase inhibitory activity

and hepatoprotective effect of 18β‑glycyrrhetinic acid from the

uralensis. Planta Med 2002;66:40‑3.

Hase K, Kasimu R, Basnet P, Kadota S, Namba T. Preventive

effect of lithospermate B from Salvia miltorhizaon experimental

hepatitis induced by carbon tetrachloride or D‑galactosamine/

lipopolysaccharide. Planta Med 1997;63:22‑6.

Kinoshita S, Inoue Y, Nakama S, Ichiba T, Aniya Y. Antioxidant and

hepatoprotective actions of medicinal herb Terminalia catappa L.

from Okinawa Island and its tannin corilagin. Phytomedicine


Chander R, Srivastava V, Tandon JS, Kapoor NK. Antihepatotoxic

activity of diterpenes of Andrographis paniculata (Kal‑megh)

against Plasmodium berghei induced hepatic damage in Mastomys

natalensis. Int J Pharmacogn 1995;33:135‑8.

Garg HS, Bhandari SP, Tripathi SC, Patnaik GK, Puri A,

Saxena R, et al. Antihepatotoxic and immunostimulant

properties of iridoid glycosides of Scrophularia koelzii. Phytother

Res 1994;8:224‑8.

Pradhan SC, Girish C. Hepatoprotective herbal drug, silymarin

from experimental pharmacology to clinical medicine. Indian J

Med Res 2006;124:491‑504.

Valan MF, Britto JD, Venkataraman R. Phytoconstituents with

hepatoprotective activity. Int J Chem Sci 2010;8:1421‑32.

Teschke R, Eickhoff A, Wolff A, Frenzel C, Schulze J. Herbal

hepatotoxicity and WHO global introspection method. Ann

Hepatol 2013;12:11‑21.

LiverTox: Clinical and research information on drug‑induced liver

injury. Available from: http://www.livertox.nih.gov/ [Last accessed

date 2013 Apr 4].

Larson AM, Chopra S, Travis AC. Hepatotoxicity due to herbal

medications and dietary supplements. Available from: http://www.


s‑and‑dietary‑supplements [Last accessed date 2013 Mar 28].

Shaw D, Leon C, Koleu S, Murray V. Traditional remedies and

food supplements. A five‑year toxicological study (1991-1995).

Drug Saf 1997;17:342‑56.

Guidelines for the assessment of herbal medicines. Available from:

http://whqlibdoc.who.int/hq/1991/WHO_TRM_91.4.pdf [Last

accessed date 2013 Jan 24].

WHO regional director for the western Pacific region working

group on herbal medicines. Available from: http://apps.who.

int/medicinedocs/en/d/Jh2945e/14.html [Last accessed on 2013

Feb 11].

DOI: http://dx.doi.org/10.22377/ijgp.v7i4.333


  • There are currently no refbacks.