Published: 2020-05-21

Comparison of hepatoprotective effect of aqueous and ethanolic extracts of Berberis lycium Royale (Sumbloo) in isoniazid induced hepatotoxicity in male mice model

Saima Rafique, Khalida Ajmal, Uzma Naeem, Akbar Waheed, Ayesha Afzal, Attiya Munir, Iffat Ara


Background: The objective of the study was to compare the hepatoprotective effect of aqueous and ethanolic extracts of stem bark of Berberis lycium Royle in isoniazid (INH) induced hepatotoxicity in mice model.

Methods: This randomized controlled in-vivo study conducted in male mice model from 10th April 2014 till 10th May 2014 at National Institute of Health, Islamabad. Group (C) was given normal diet and water. Group (D) was given isoniazid (50 mg/kg BW) to produce hepatotoxicity. Group (LA) and (HA) were given isoniazid (INH) plus low and high dose of aqueous extract of stem bark of Berberis lycium Royle respectively. Group (L.E) and (H.E) were given INH plus low and high dose of ethanolic extract of stem bark of Berberis lycium Royle respectively.

Results: Hepatotoxicity produced by INH was shown by raised serum liver function tests (LFT’s), marked hepatocytic ballooning, significant steatosis and inflammation. Mice receiving simultaneous treatment of INH, low and high dose of aqueous extract of Berberis lycium Royle showed decrease serum LFT’s and their liver sections showed improved histological picture but more significant reduction in hepatotoxic effects were observed in animals receiving low and high doses of ethanolic extract.

Conclusions: Hepatotoxicity of INH can be more fully reversed by simultaneous use of INH with ethanolic extract as it has better hepatoprotective potential in dose dependent manner as compare to aqueous extract of stem bark of Berberis lycium Royle.


Berberis lycium Royale, Aqueous extracts, Ethanolic extracts, Hepatoprotective, Isoniazid, LFT’s

Full Text:



Jagielski T, Minias A, Ingen VJ, Rastogi N, Brzostek A, Zaczek A, et al. Methodological and clinical aspects of the molecular epidemiology of Mycobacterium tuberculosis and other mycobacteria. Clin Microbiol Rev. 2016;29(2):239-90.

Phelan E, Gammal EA, Connor OTM. Tuberculosis. In: Encyclopedia of Environmental Health; 2019.

Murray JF, Schraufnagel DE, Hopewell PC. Treatment of tuberculosis: a historical perspective. Annals Am Thoracic Society. 2015;12(12):1749-59.

Jenkin G, Sheffield D. Isoniazid, In: Kucers the Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, Seventh Edition; 2017.

Isa SE, Ebonyi AO, Shehu NY, Idoko P, Okopi AJA, Simji G, et al. Antituberculosis drugs and hepatotoxicity among hospitalized patients in Jos, Nigeria. Int J Mycobacteriology. 2016;5(1):21-6.

Wang P, Pradhan K, Zhong XB, Ma X. Isoniazid metabolism and hepatotoxicity. Acta Pharmaceutica Sinica B. 2016;6(5):384-92.

Amir M, Khan MA, Ahmad S, Akhtar M, Mujeeb M, Ahmad A, et al. Ameliorating effects of Tamarindus indica fruit extract on anti-tubercular drugs induced liver toxicity in rats. Nat Prod Res. 2016;30(6):715-9.

Gourishankar A, Navarro F, Roy DAN, Smith KC. Isoniazid hepatotoxicity with clinical and histopathology correlate. Ann Clin Lab Sci. 2014;44(1):87-90.

Jahan S, Imran S, Ahsan N. Isoniazid Induced Liver Damage. Prof Med J. 2018;25(07):1124-8.

Kilmer PD. Book review: development theory and practice: critical perspectives. J Theory Pract Crit. 2010;11(3):369-73.

Murad W, Ahmad A, Gilani SA, Khan MA. Indigenous knowledge and folk use of medicinal plants by the tribal communities of Hazar Nao forest, Malakand district, North Pakistan. J Med Plants Res. 2011;58(4):697-704.

Id A, Author C. Antimicrobial and Anti-inflammatory Activities of Bark of Four Plant Species from Indian Origin Antimicrobial and Anti-inflammatory Activities of Bark of Four Plant Species from Indian Origin. Evid Based Complement Alternat Med. 2012;2012:1-14.

Yin J, Zhang H, Ye J. Traditional Chinese Medicine in Treatment of Metabolic Syndrome. Endocrine‚ Metab Immune Disord Targets. 2008;8(2):99-111.

Girish C, Koner BC, Jayanthi S, Rao RK, Rajesh B, Pradhan SC. Hepatoprotective activity of picroliv, curcumin and ellagic acid compared to silymarin on paracetamol induced liver toxicity in mice. Fundam Clin Pharmacol. 2009;23(6):735-45.

Basheer AS, Siddiqui A, Paudel YN, Hassan MQ, Imran M, Najmi AK, et al. Hepatoprotective and antioxidant effects of fish oil on isoniazid-rifampin induced hepatotoxicity in rats. Pharma Nutrition. 2017;5(1):29-33.

Khan MA, Jehanzeb, Shafiullah, Malik SA, Shafi M. Hepatoprotective effects of berberis lycium, galium aparine and pistacia integerrima in carbon tetrachloride (CCL4)-treated rats. JPMI - J Postgrad Med Inst. 2008;22(2):91-4.

Mashwani ZR, Khan MA, Irum S, Ahmad M. Antioxidant potential of root bark of Berberis lycium Royle. from Galliyat, western Himalaya, Pakistan. Pakistan J Bot. 2013;45:231-4.

Young DS. Effects of drugs on clinical laboratory tests. Am Association Clin Chemistry; 1995.

Pandit A, Sachdeva T, Bafna P. Drug-induced hepatotoxicity: a review. J Appl Pharm Sci. 2012;2(5):233-43.

Zuberi BF, Zuberi FF, Bader N, Alvi H, Salahuddin J. Comparison of British Thoracic Society and American Thoracic Society reintroduction guidelines for anti-tuberculous therapy induced liver injury. J Pak Med Assoc. 2014;64(8):896-9.

Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, et al. Official American thoracic society/centers for disease control and prevention/infectious diseases society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016;63(7):147-95.

Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci. 2015;16(11):26087-124.

Zumla A, Chakaya J, Centis R, Ambrosio DL, Mwaba P, Bates M, et al. Tuberculosis treatment and management: an update on treatment regimens, trials, new drugs, and adjunct therapies. Lancet Respir Med. 2015;3(3):220-34.

Hoareau L, DaSilva EJ. Medicinal plants: a re-emerging health aid. Electron J Biotechnol. 1999;2(2):3-4.

Jabeen N, Saleem A, Anwaar S, Hussain Z. Berberis lycium Royle (Royle, 1837): a threatened medicinal plant and Its biological activities. EC Agric. 2015;1(2):100-8.

Chand N, Durrani FR, Ahmad S, Khan A. Immunomodulatory and hepatoprotective role of feed‐added Berberis lycium in broiler chicks. J Sci Food Agric. 2011;91(10):1737-45.

Hwang JM, Wang CJ, Chou FP, Tseng TH, Hsieh YS, Lin WL, et al. Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat liver. Arch Toxicol. 2002;76(11):664-70.

Ojo OA, Oloyede OI, Olarewaju OI, Ojo AB, Ajiboye BO, Onikanni SA. In-vitro antioxidant and free radical scavenging activities of Ocimum Gratissimum. Wr J Pharma Res. 2013;2(6):1899-912.

Fayed AHM, Salama AAA, Ismaiel IE, Attia TA, Hassan A. Protective Effects of Solanium Nigrum Methanolic Extract Against Isoniazid/Rifampicin Induced Hepatotoxicity in Rats. J Appl Vet Sci. 2019;4(2):52-61.

Ahmad M. Hepato-curative effect of barriers lycium (Royle) in hepatotoxic rabbits. Gomal Univ J Res. 2008;24(1):1-9.

Ahmed A. Biochemical Studies on Berberis Lyceum Royal and Analysis of its Extracts for Bioactivity. Arid Agriculture University Rawalpindi, Pakistan; 2009.

Imber CJ, Peter SD, Handa A, Friend PJ. Hepatic steatosis and its relationship to transplantation. Liver Transplant. 2002;8(5):415-23.

Church RJ, Wu H, Mosedale M, Sumner SJ, Pathmasiri W, Kurtz CL, et al. A systems biology approach utilizing a mouse diversity panel identifies genetic differences influencing isoniazid-induced microvesicular steatosis. Toxicol Sci. 2014;140(2):481-92.

Livadariu RM, Danila R, Ionescu L, Ciobanu D, Timofte D. Study of Biochemical and Clinical Markers in Steatohepatitis Related to Obesity. Rev Chim. 2018;69(6):1501-5.

Hassan AS, Ahmed JH, Haroon ASS. A study of the effect of Nigella sativa (black seeds) in isoniazid (INH)-induced hepatotoxicity in rabbits. Indian J Pharmacol. 2012;44(6):678.

Ahmed S, Shakeel F. Voltammetric determination of antioxidant character in Berberis lycium Royel, Zanthoxylum armatum and Morus nigra Linn plants. Pak J Pharm Sci. 2012;25(3):501-7.