Hepatotoxicity and Hepatoprotective agents : A Mini review

  • Mudasir Maqbool University of Kashmir
  • Shafiqa Rasool University of Kashmir
  • Mohmad Amin Dar University of Kashmir
  • Rabiah Bashir University of Kashmir
  • Misba Khan Mader-E-Meharban Institute of Nursing Sciences and Research
Keywords: Liver, Hepatotoxic, hepatoprotective, herbal formulations


The maintenance of a healthy liver is vital to overall health of the human beings. Since the liver is involved in almost all biochemical processes and there are many different diseases that will affect it. The liver is often abused by environmental toxins, which are eating habits, alcohol and overdose of certain drugs which can damage and weaken the liver and eventually lead to many diseases. Medicinal herbs are significant source of hepatoprotective drugs. Mono and poly-herbal preparations have been used in various liver disorders. According to one estimate, more than 700 mono and poly-herbal preparations in the form of decoction, tincture, tablets and capsules from more than 100 plants are in clinical use. From the literature review near about 178 medicinal plants are reported to possess a hepatoprotective activity. A drug having beneficial effect on the liver is known as hepatoprotective drug. On the other hand, drugs having toxic effect on the liver are better known as hepatotoxic drugs. The most commonly used parameters to assess the hepatoprotective activity are morphological e.g. Liver weight and volume, biochemical estimations, such as measurement of transaminase activity, SGPT, SCOT, alkaline phosphatase, serum bilirubin, total serum proteins, albumin, globulin and prothrombin time, functional parameters, pentobarbitone and hexobarbitone sleeping time and finally histopathological study regarding presence of necrosis, fatty degeneration and cirrhosis. In this review, we will briefly discuss hepatotoxicity and hepatoprotective agents.

Author Biographies

Mudasir Maqbool, University of Kashmir

Department of Pharmaceutical Sciences,
University of Kashmir,
Hazratbal Srinagar, Jammu and Kashmir, India

Shafiqa Rasool, University of Kashmir

Department of Pharmaceutical Sciences,
University of Kashmir,
Hazratbal Srinagar, Jammu and Kashmir, India

Mohmad Amin Dar, University of Kashmir

Department of Pharmaceutical Sciences,
University of Kashmir,
Hazratbal Srinagar, Jammu and Kashmir, India

Rabiah Bashir, University of Kashmir

Department of Pharmaceutical Sciences,
University of Kashmir,
Hazratbal Srinagar, Jammu and Kashmir, India

Misba Khan, Mader-E-Meharban Institute of Nursing Sciences and Research

Mader-E-Meharban Institute of Nursing Sciences and Research,
Jammu And Kashmir, India


1. Adikwu E. and Deo O. (2013) “Hepatoprotective Effect of Vitamin C (Ascorbic Acid)” Journal of Pharmacology & Pharmacy 4(1): 84-92.
2. Akila M. and Prasanna G. (2014) “Hepatoprotective Effect of Indigofera Linnael Ali. On Carbon Tetrachloride Induced Wistar Albino Rats” International Research Journal of Pharmacy 5(5): 392-395.
3. Adamska T., Młynarczyk W., Jodynis-Liebert J., Bylka W. Matławska I. (2003) “Hepatoprotective Effect of the Extract and Isocytisoside from Aquilegia vulgaris Phytotherapy Research 17(6): 691-696.
4. Bishayee, A., Sarkar, A. and Chatterjee (1995), Hepatoprotective activity of carrot (Daucus Carota) against carbon tetrachloride intoxication in mouse liver, J Ethnopharmacol, 47: 69-74.
5. Bedi O., Bijjem K.R.V., Kumar P., Gauttam V. (2016) “Herbal Induced Hepatoprotection and Hepatotoxicity: A Critical Review” Indian Journal of Physiological Pharmacology 60(1): 6-21.
6. Bahar E., Ara J., Hossain M., Nath B., Runi N. (2013) “Cytotoxic (In-Vitro) Effect of Methanol and Petroleum Ether Extracts of the Aerva lanata” Journal of Pharmacognosy and Phytochemistry 2(1): 92-100.
7. Bigoniya P., Singh C. S., Shukla A., (2009) “A Comprehensive Review of Different Liver Toxicants Used in Experimental Pharmacology” International Journal of Pharmaceutical Sciences and Drug Research 1(3): 124-135.
8. Chaudhury R.R. and Refei U.M. (2001) “Traditional Medicine in Asia” New Delhi, WHO Regional Office for South-East Asia, World Health Organization Regional Publication No.39, ISBN 92 9022 2247.
9. Chattopadhyay, R. R., Sarkar, S. K., Ganguly, S., Benerjee, R. N., Basu, T. K. and Mukherjee, A. (1994), Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats, Indian J Pharmacol, 26: 35-40.
10. Chattopadhyay, R. R., Sarkar, S. K., Ganguly, S., Medda, C. and Basu, T. K. (1992), Hepatoprotective activity of Ocimum sanctum leaf extract against paracetamol induced hepatic damage in rats. Indian J Pharmacol, 24: 163-165.
11. Chang C.Y and Schiano T.D. (2007) “Review Article: Drug Hepatotoxicity” Journal of Alimentary Pharmacology & Therapeutics 25(10): 1135-1151.
12. Dwivedi, Y., Rastogi, R., Garg, N. K. and Dhawan, B. N. (1991), Prevention of paracetamol induced hepatic damage in rats by picroliv, the standard active fraction from Picrorhiza kurroa, Phytother Res, 5:115-119.
13. Das A., Biswas P., Chakrabarty P. (2011) “Hepatotoxicity and Hepatoprotective Herbs: Herbal Remidies” International Journal of Research in Ayurveda and Pharmacy 2(4): 1073-1078.
14. Fatma N. and Uphadhyay R.P. (2015) “Euphorbia Nivulia Buch. Ham.: A Boon for Jaundice (A Case Study)” Annals of Plant Sciences 4(6): 1137-1139.
15. Flatland B. (2003) “Botanicals, Vitamins, and Minerals and the Liver: Therapeutic Applications and Potential Toxicities” Compendium on Continuing Education for the Practising Veterinarian Practitioners 25(7): 514-524.
16. Flora K., Hahn M., Rosen H., Benner K. (1998) “Milk Thistle (Silybum marianum) for the Therapy of Liver Disease” The American Journal of Gastroenterology 93(2): 139-143.
17. Gulati, R. K., Agrawal, S. and Agrawal, S. S. (1994), Hepatoprotective studies on Phyllanthus emblica Linn and quercetin, Ind J Expt Biol, 33: 261- 268.
18. Gawhare V.S. (2013) “A Review on Guduchi through Ayurvedic Texts” International Ayurvedic Medical Journal 1(3): 1-7.
19. Gadgoll, C. and Mishra, S.H. (1995), Preliminary screening of Achillea millefolium, Cichorium intybus and Capparis spinosa for anti- hepatotoxic activity, Fitother, 66: 319-323.
20. Girish C., Koner B.C., Jayanthi S., Rao K.R., Rajesh B., Pradhan S.C. (2009) “Hepatoprotective Activity of Six Polyherbal Formulations in Paracetamol Induced Liver Toxicity in Mice” Indian Journal of Medical Research 129(5): 569-578.
21. Ho W. Y., Yeap S.K., Ho C.L., Rahim R.A., Alitheen N.B. (2012) “Hepatoprotective Activity of Elephantopus scaber on Alcohol-Induced Liver Damage in Mice” Evidence-Based Complementary and Alternative Medicine 417953: 8.
22. Hermenean A., Stan M., Ardelean A., Pilat L., Mihali C.V., Popescu C., Nagy L., Deak G., Zsuga M., Keki S., Bacskay I., Fenyvesi F., Costache M., Dinischiotu A., Miklos V. (2015) “Antioxidant and Hepatoprotective Activity of Milk thistle (Silybum marianum L. Gaertn.) Seed Oil” Life Sciences 10(1):225-236.
23. Handa S. S., Sharma. A. and Chakraborty, K. K. (1986), Natural products and plants as liver protecting drugs, Fitother, 57: 307-351.
24. Handa S. S. and Sharma. A. (1990), Hepatoprotective activity of andrograpolide against galactosamine and paracetamol intoxication in rats, Indian J Med Plant, 92: 284-292.
25. Hegde, K. and Joshi, A. B. (2009), Hepatoprotective effect of Carissa carandus Linn root extract against CCl4 and paracetamol induced hepatic oxidative stress, Indian j Expt Biol, 47: 660- 666.
26. Jayasekhar, P., Mohanan, P.V. and Rathinum, K. (1997), Hepatoprotective property of ethyle acetate extract of Acacia catechu, Indian J Pharmacol, 29: 426-428.
27. Johnson M., Olufunmilayo L.A., Anthony D.O., Olusoji E.O. (2015) “Hepatoprotective Effect of Ethanolic Leaf Extract of Vernonia amygdalina and Azadirachta indica against Acetaminophen-Induced Hepatotoxicity in Sprague-Dawley Male Albino Rats” American Journal of Pharmacological Sciences 3(3): 79-86.
28. Jia J.D., Bauer M., Cho J.J., Ruehl M., Milani S. Boigk G., Riecken E.O., Schuppan D. (2001) “Antifibrotic Effect of Silymarin in Rat Secondary Biliary Fibrosis is Mediated by Downregulation of Procollagenα1 (I) and TIMP-1” Journal of Hepatology 35(3): 392-398.
29. Lee W.M. (2003) “Drug-Induced Hepatotoxicity” The New England Journal of Medicine 349(5): 474-485.
30. Maheswari E., Saraswathy G.R., Thakur Santhranii T. (2014) “Hepatoprotective and Antioxidant Activity of N-acetyl Cysteine in Carbamazepine-Administered Rats” Indian Journal of Pharmacology 46(2): 211-215.
31. MeMahon B.J. (2005) “Epidemiology and Natural History of Hepatitis B” Seminars in Liver Disease 25(1): 3-8.
32. Mohd J., Akhtar A.J. Abuzer A., Tajuddin T.E., Sayeed S. (2012) “Hepatoprotective Evidence of Higher Altitude Medicinal Plant Picrorhiza kurroa Royle Ex Benth: Threatened with Extinction” Journal of Herbal Medicine and Toxicology 6 (2): 1-5.
33. Nasir A., Abubakar M.G., Shehu R.A., Aliyu U., Toge B.K. (2013) “Hepatoprotective Effect of the Aqueous Leaf Extract of Andrographis paniculata Nees against Carbon Tetrachloride Induced Hepatotoxicity in Rats” Nigerian Journal of Basic and Applied Science 21(1): 45-54.
34. Navarro V.J. and Senior J.R. (2006) “Drug-Related Hepatotoxicity” The New England Journal of Medicine 354(7): 731-739.
35. Onyije F. M. And Avwioro O. G. (2012) “Effect of Ethanolic Extract of Bauhinia Monandra Leaf on the Liver of Alloxan Induced Diabetic Rats” Journal of Physiology and Pharmacology Advances 2(1): 59-63.
36. Ostapowicz G., Fontana R.J., Schiodt F.V., Larson A., Davern T.J., Han S.H., McCashland T.M., Shakil A.O., Hay J.E., Hynan L. (2002) “Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States” Annals of Internal Medicine 137(12): 947-954.
37. Pandit A., Sachdeva T., Bafna P. (2012) “Drug-Induced Hepatotoxicity: A Review” Journal of Applied Pharmaceutical Science 2 (5): 233-243.
38. Papay J.I., Clines D., Rafi R., Yuen N., Britt S.D., Walsh J.S., Hunt C.M. (2009) Drug-Induced Liver Injury Following Positive Drug Rechallenge” Regulatory Toxicology and Pharmacology 54(1): 84-90.
39. Pascual C., Gonz R., Armesto J., Muriel P. (1993) “Effect of Silymarin and Silybinin on Oxygen Radicals” Drug Development Research 29(1): 73-77.
40. Pradhan S.C. and Girish C. (2006) “Hepatoprotective Herbal Drug, Silymarin from Experimentalpharmacology to Clinical Medicines” Indian Journal of Medical Research 124(5): 491-504.
41. Pandey S., Gujrati V.R., Shanker K., Singh N., Dhawan K.N. (1994) “Hepatoprotective Effect of Liv.52 Against CVl4-Induced Lipid Peroxidation in Liver of Rats” Indian Journal of Experimental Biology 32(9): 674-675.
42. Reddy, B. P., Murthy, V. N., Venkateshwarlu, V., Kokate, C. K. and Rambhau, D. (1993), Antihepatotoxic activity of Phyllanthus niruri, Tinospora cordifolia and Ricinus communis, Indian Drugs, 87: 401-404.
43. Ravikumar V., Shivashangari K.S., Devaki T. (2006) “Effect of Tridax procumbens on Liver Antioxidant Defense System during Lipopolsaccharid- Induced in Dgalactosomine Sensitized Rats” Molecular and Cellular Biochemistry 269(1-2): 131-136.
44. Rajaratnam M., Prystupa A., Lachowska-Kotowska P., Załuska W., Filip R. (2014) “Herbal Medicine for Treatment and Prevention of Liver Diseases” Journal of Pre-Clinical and Clinical Research 8(2): 55-60.
45. Sanmugapriya E. and Venkataraman S. (2006) “Studies on Hepatoprotective and Antioxidant Actions Ofstrychnos potatorum Linn. Seeds on CCl4-Induced Acute Hepatic Injury in Experimental Rats” 105(1-2): 154-160.
46. Saxena, A. K., Singh, B. and Anand, K. K. (1993), Hepatoprotective effects of Eclipta alba on sub cellular levels in rats, J Ethnopharmacol, 40: 155-161.
47. Shah, M., Patel, P., Phadke, M., Menon, S., Mary, F. and Sane, R. T. (2002), Evaluation of the effect of aqueous extract from powders of root , stem, leaves and whole plant of Phyllanthus debilis against CCl4 induced rat liver dysfunction, Ind Drugs, 39: 333- 337.
48. Sharma V. and Pandy D. (2010) “Protective Role Tinospora cordifolia against Lead-Induced Heptotoxicity” Toxicology 17(1): 12-17.
49. Sharma V. and Agrawal R.C. (2014) “In Vivo Antioxidant and Hepatoprotective Potential of Glycyrrhiza Glabra Extract on Carbon Tetrachloride (CCl4) Induced Oxidative-Stress Mediated Hepatotoxicity” International Journal of Research in Medical Sciences 2(1): 314-320.
50. Saller R., Meier R., Brignoli R. (2001) “The Use of Silymarin in the Treatment of Liver Diseases” Drugs 61(14): 2035-2063.
51. Sharma A., Singh R.T., Sehgal V., Handa S.S. (1991) “Antihepatotoxicity Activity of Some Plants Used in Herbal Formulations” Fitoterapia 62: 131-138.
52. Singh D., Cho W.C. and Upadhyay G. (2016) “Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview” Frontiers in Physiology 6: 363-381.
53. Sartor L.L. and Trepanier L.A. (2003) “Rational Pharmacologic Therapy of Hepatobiliary” Compendium on Continuing Education for the Practising Veterinarian 25(6): 432-445.
54. Singh A., Bhat T.K., Sharma O.P. (2011) “Clinical Biochemistry of Hepatotoxicity” Journal of Clinical Toxicology 4(1): 1-19.
55. Twedt D.C. (2004) “The Use of Nutraceutical in Liver Disease” Proceedings of the 28th Annual Royal Canin/OSU Symposium. Columbus, Oct 16-17: 63-66.
56. Vargas-Mendoza N., Madrigal-Santillan E, Morales-González A, Esquivel-Soto H, Esquivel-Chirino C, González-Rubio G.M., Gayosso-de-Lucio J.A. (2014) “Hepatoprotective effect of silymarin” World Journal of Hepatology 6(3): 144-149.
57. Wang F.S., Fan J.G., Zhang Z., Gao B., Wang H.Y. (2014a) “The Global Burden of Liver Disease: The Major Impact of China” Hepatology 60(6): 2099-2108.
58. Willett K.L., Roth R.A., Larry Walker L. (2004) “Workshop Overview: Hepatotoxicity Assessment for Botanical Dietary Supplements” Toxicological Sciences 79 (1): 4-9.
59. Yapar K., Kart A., Karapehlivan M., Atakisi O., Tunca R., Erginsoy S., Citil M. (2007) “Hepatoprotective Effect of L-Carnitine against Acute Acetaminophen Toxicity in Mice” Experimental and Toxicologic Pathology 59(2): 121-128.
How to Cite
Maqbool, M., Rasool, S., Dar, M., Bashir, R. and Khan, M. 2019. Hepatotoxicity and Hepatoprotective agents : A Mini review. PharmaTutor. 7, 9 (Sep. 2019), 34-40.

Most read articles by the same author(s)