Document Type : Research Paper

Author

Himalayan Institute of Pharmacy & Research

Abstract

The liver is a vital organ that plays a major role in the metabolism and excretion of xenobiotics from the body. Liver injury or liver dysfunction is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. Liver cell injury caused by various toxic chemicals (certain antibiotics, chemotherapeutic agents, carbon tetrachloride, thioacetamide, excessive alcohol consumption, and microbes are well-studied. The available synthetic drugs to treat liver disorders in this condition also cause further damage to the liver. Hence, Herbal drugs have become increasingly popular and their use is widespread. Herbal medicines have been used in the treatment of liver diseases for a long time so the maintenance of a healthy liver is essential for the overall well-being of an individual. Various herbal medicines are available in the market. The liver is the largest solid organ in the upper abdomen that aids in digestion and removes waste products and worn-out cells from the blood. Liver injury or liver dysfunction is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. Liver injury induced by toxins is more common nowadays. Herbal remedies are focused in the pharmaceutical industry to evolve a safe route for liver disorders. The present review is aimed at compiling data on promising phytochemicals from medicinal plants that have been tested in hepatotoxicity models using the modern scientific system.

Keywords

Main Subjects

  1. References

     

    1. Abdel-razik AF, Elshamya A-SI, Nassar, MI, El-Kousy SM, Hamdy H. Chemical constituents and hepatoprotective activity of Juncus subulatus Rev. Latinoamer. Quim. 2009; 37: 70-84.
    2. Achuthan CR, Babu BH, Padikkala J. Antioxidant and Hepatoprotective effects of Rosa damascene. Pharmaceut Biol. 2003; 41: 357-361.
    3. Afaf I, Abuelgasim, Nuha HS, Mohammed AH. Hepatoprotective effect of Lepidium sativum against carbon tetrachloride-induced damage in rats. Res J Animal Veterinary Sci. 2008; 3: 20-23.
    4. Agarwal AK, Mehendale JK. Potentiation of carbon tetrachloride hepatotoxicity and lethality by chlordecone in female rats. Toxicol. 1983; 26:231-42.
    5. Agarwal SS. Development of hepatoprotective formulations from plant sources. In: Pharmacology and Therapeutics in the New Millennium. Edited by Gupta SK, Narosa Publishing House, New Delhi, 2001, 357-358.
    6. 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: 313–316.
    7. Ahsan R, Islam MK, Musaddik A, Haque E. Hepatoprotective Activity of Methanol Extract of Some Medicinal Plants Against Carbon Tetrachloride Induced Hepatotoxicity in Albino Rats. Global J Pharmacol. 2009; 3(3):116-122.
    8. Ajay KG, Neelam M. Hepatoprotective activity of aqueous and ethanolic extract of Chamomile capitula in Paracetamol-intoxicated albino rats. Am J Pharmacol Toxicol. 2006; 1(1): 17-20.
    9. Al Eid A, Al-Asmary SM. A Review of Hepatoprotective Plants Used in Saudi Traditional Medicine. Evid Based Complement Alternat Med. 2014; 2014: 890842.
    10. Ali AS, Gameel AA, Mohamed AH, Hassan T. Hepatoprotective activity of Capparis decidua aqueous and methanolic stems extracts against carbon tetrachloride induced liver histological damage in rats. J Pharmacol Toxicol. 2010; 6(1): 62-68.
    11. Ali M, Khan T, Fatima K, Ali QA, Ovais M, Khalil AT, Ullah I, Raza A, Shinwari ZK, Idrees M. Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions. Phytother Res. 2018; 32(2): 199–215. 
    12. Ali SA, Sharief NH, Mohamed YS. Hepatoprotective Activity of Some Medicinal Plants in Sudan. Evid Based Complement Alternat Med. 2019; 2019: 2196315.
    13. Aniya Y, Miyagi A, Nakandakari, Kamiya N, Imaizumi N, Ichiba T. Free radical scavenging action of the medicinal herb Limonium wrightii from the Okinawa islands. Phytomed. 2002; 9: 239-244.
    14. Ansari RA, Tripathi SC, Patnaik GK, Dhawan BN. Antihepatotoxic properties of picroliv: an active fraction from rhizomes of Picrorhiza kurrooa. J Ethnopharmacol. 1991; 34(1): 61-8.
    15. Anubha SS. Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against Paracetamol and thioacetamide intoxication in rats. J Ethnopharmacol. 1995; 49(3):119-126.
    16. Arulkumaran KS, Rajasekaran A, Ramasamy A, Jegadee-san M, Kavimani S, Somasundaram A. Cassia rox-burghii seeds protect liver against toxic effects of ethanol and carbontetrachloride in rats. Int J Pharm-Tech Res. 2009; 1(2): 273-246.
    17. Asha VV. Preliminary studies on the hepatoprotective activity of Mamordica subangulata and Naragamia alata. Indian J Pharmacol. 33; 2001: 276-279.
    18. Bahar A, Tanveer A, Shah AK. Hepatoprotective activity of Luffa echinata fruits. J Ethanopharmacol. 2001; 76:87-89.
    19. Bardhan P, Sharma SK, Garg NK. In vitro effect of an ayurvedic liver remedy on hepatic enzymes in carbon tetrachloride treated rats. Indian J Med Res, 1985; 82:359-364.
    20. Bhakta T, Banerjee S, Subhash C. M, Tapan K. Maity, Saha B.P, Pal M. Hepatoprotective activity of Cassia fistula leaf extract. Phytomed. 8; 2001: 220-24.
    21. Budavari S. The Merck Index: An Encyclopedia of Chemicals, Drugs and Biological, 12th Edition, New York Merck & Co. Inc, Whitehouse Station, 1996: 1674.
    22. Cameron GR, Thomas JC, Karunara the WAE. The pathogenesis of liver injury in carbon tetrachloride and thioacetamide poisioning. J Path Bact. 41; 1936: 41: 297
    23. Chander R, Dwivedi Y, Rastogi R, Sharma SK, Garg NK, Kapoor NK, Dhawan BN Evaluation of hepatoprotective activity of picroliv from Picrorhiza kurroa in Mastomys natalensis infected with Plasmodium berghei. Int J Medicinal Res. 92; 1990: 34-7.
    24. Chandra T, Sadique J, Soma Sundram S. Effect of Eclipta alba on inflammation and liver injury. Fitoterapia. 1987; 58(1): 23-32.
    25. Chang-Chi H, Hsun-Lang F, Wen-Chuan L. Inhibitory effect of Solanum nigrum on thioacetamide-induced liver fibrosis in mice. J Ethnopharmacol. 2008; 119: 117–121.
    26. Chaterjee TK. Medicinal Plants with Hepatoprotective Properties, Herbal Options, Books & Allied (P) Ltd, Calcutta, 2000:155.
    27. Chattopadhyay RR, Sarkar SK, Ganguly S, Banerjee RN, Basu TK, Mukherjee A. Hepatoprotective activity of Azadirachta indica leaves on Paracetamol induced hepatic damage in rats. Indian J Exp Biol. 1992; 30(8): 738-40.
    28. Chopra RN, Nayar SL, Chopra IC. In: Glossary of medicinal plants, SIR Publication, New Delhi, 1966: 104.
    29. Clawson GA. Mechanisms of carbon tetrachloride hepatotoxicity. Pathol Immunopathol Res, 1989; 8(2): 104-12.
    30. Daoudi NE, Bnouham M. Hepatoprotective Essential Oils: A Review. J Pharmacopuncture. 2020; 23(3): 124–141.
    31. Das PK, Prasanna P, Somya RP, Ranjan S. Hepatoprotective activity of plant argemon mexicana against CC14 induced hepatotoxicityin rats. Int J Pharm Res develop. 2009; 8: 002-003.
    32. Dawkins MJR. J. Path. Bact. Potentiation of Carbon Tetrachloride Toxicity by Dimethyl Sulphoxide, 1963; 85: 189.
    33. Dhanabal SP, Syamala G, Satish KMN, Suresh B. Hepatoprotective activity of the Indian medicinal plant Polygala arvensis on d-galactosamine-induced hepatic injury in rats. Fitoterapia. 2006; 77(6): 472-474.
    34. Dubey SK, Batra A. Hepatoprotective Activity from ethanolfraction of Thuja occidentalis Linn. Asian J Res Chem. 2008; 1(l): 32-35.
    35. El-Wahab AEA, El-Adawi H, kassem HS. Towards Understanding the Hepatoprotective effect of Grape Seeds Extract on Cholesterol-Fed Rats. Aust J Basic Appl Sci,2008; 2: 412-417.
    36. Godgoli C, Mishra SH. Antihepatotoxic activity of Cinchorium intybus. J Ethnopharmacol. 1997; 58: 131-134.
    37. Gond NY, Kadabadi SS. Hepatoprotective Activity of Ficus carica Leaf Extract on Rifampicin-Induced Hepatic Damage in Rats. Indian J Phanna Sci. 2008; 70(3): 364-366.
    38. Gupta AK, Chitme H, Dass SK, Misra N. Antioxidant activity of Chamomile recutita capitula methanolic extracts against CCl4-induced liver injury in rats. J Pharmacol & Toxicol. 2006; 1(b): 101-107.
    39. Gupta AK, Misra N. Hepatoprotective activity of aqueous ethanolic extract of Chamomile capitula in Paracetamol intoxicated albino rats. Am J Pharmacol Toxicol, 2006; 1(1): 17-20.
    40. Gupta N.K, Dixit V.K. Evaluation of hepatoprotective activity of Cleome viscosa Linn. Extract. Indian J Pharmacol, 2009; 41: 36-40.
    41. Handa SS, Sharma A, Chakraborti KK. Natural products and plants as liver protecting drugs. Fitoterapia. 1986; 57(5): 307-352.
    42. Handa SS, Sharma A. Hepatoprotective activity of Andrographolide from Andrographis paniculata against carbon tetrachloride. Ind J Med Res. 1990; 92: 276-92.
    43. Harshmohan. The liver, biliary tract and exocrine pancreas. In: Text book of pathology, 4th Ed, Jaypee Brothers Medical Publishers (P) Ltd. New Delhi. 2002; 22-4 and 569-630.
    44. http://www.cmjournal.org/content/5/1/33
    45. Hui-Mei L, Hsien-Chun T, Chau-Jong W, Jin-Jin L, Chia- Wen L, Fen-Pi C. Hepatoprotective effects of Solanum nigrum Linn extract against CCl4-iduced oxidative damage in rats. Chemico Biological Interactions. 2008; 171: 283–293.
    46. Ilyas U, Katare, D.P, Aeri, V, Naseef P.P. A Review on Hepatoprotective and Immunomodulatory Herbal Plants. Pharmacogn Rev. 2016; 10(19): 66-70.
    47. Jain SK, Rajvaidy S, Desai P, Singh GK, Nagori BP. Herbal Extract as Hepatoprotective-A Review. J Pharmacog Phytochem. 2013; 2(3): 170-175.
    48. Jamshidzadeh A, Khoshnoud MJ, Dehghani Z, Niknahad H. Hepatoprotective Activity of Cichorium Intybus L. Leaves Extract against Carbon Tetrachloride Induced Toxicity. Iran J Pharm Res. 2006; 5(1): 41-46.
    49. Kalantari H, Rastmanesh M. Protective Property of Cichorium Intybus in CCl4 Induced Liver Damage in mice. School of Pharmacy, Ahwaz University of Medical Sciences, Ahwaz, 2008, Iran.
    50. Kanchana N, Sadiq MA. Hepatoprotective effect of Plumbago zeylanica on Paracetamol induced liver toxicity in rats. Int J Pharm Pharm Sci. 2011; 3: 151-154.
    51. Kapoor LD, CRC Handbook of Ayurvedic Medicinal Plants, Boca Raton, CRC Press, 1990: 149-150.
    52. Kapur V, Pillai KK, Hussain SZ, Balani DK. Hepatoprotective activity of Jigrine on liver damage caused by alcohol-carbon tetrachloride and Paracetamol in rats. Ind J Pharmacol. 1994; 26: 35-40.
    53. Karan M, Vasisht K, Handa SS. Antihepatotoxic activity of Swertia chirata on Paracetamol and galactosamine induced hepatotoxicity in rats. Phytother Res. 1999; 13(2):95-101.
    54. Karandikar SM, Joglekar GV, Chitale GK, Balwani JH. Protection by indigenous drugs against hepatotoxic effects of CCl4 a long term study. Acta Pharmacologia et toxicologia. 1963; 20: 274-280.
    55. Karthikeyan M, Wawdhane SS, Kannan M, Rajasekar S. Hepatoprotective activity of ethanolic extract of spermacoce hispida.linn against carbon tetrachloride (CCl4) induced hepatotoxicity on albino wistar rats. Int J Pharm Res develop. 2006; 2: 45-52.
    56. Kaviarasan S, Ramamurty N, Gunasekaran P, Varalakshmi E, Anuradha CV. Fenugreek (Trigonella foenum graecum) seed extract prevents ethanol-induced toxicity and apoptosis in chang liver cells. Alcohol Alcoholism. 2006; 41(3): 267–273.
    57. Khosla P, Gupta DD, Nagpal RK. Effect of Trigonella foenum graecum (Fenugreek) on serum lipids in normal and diabetic rats. Inter J Pharmacol. 1995; 27: 89–93.
    58. Kokate CK, Purohit AP, Gokhale SB. Pharmacognosy. 37th ed. Nirali Prakashan, 2006: 232, 233, 248, 249, 251.
    59. Krepkova LV, Babenko AN, Saybel, OL, Lupanova IA, Kuzina OS, Job KM, Sherwin CM, Enioutina EY. Valuable Hepatoprotective Plants-How Can We Optimize Waste Free Uses of Such Highly Versatile Resources? Front Pharmacol. 2021; 12: 738504. 
    60. Krishna MG, Pallavi E, Ravi KB, Ramesh M, Venkatesh S. Hepatoprotective activity of Ficus carica (Linn) leaf extract against carbon tetrachloride-induced hepato-toxicity in rats. Daru. 2007; 15(3): 162-167.
    61. Kumar A. A review on hepatoprotective herbal drugs. Int J Res Pharm Chem. 2012; 2(1): 92-102.
    62. Lee MK, Yeo H, Kim J, and Kim YC. Protection of rat hepatocytes exposed to CCl4 in-vitro by cynandione A, a biacetophenone from Cynanchum wilfordii. J Pharm Pharmacol. 2000; 52(3): 341-5.
    63. Madani H, Talebolhosseini M, Asgary S, Nader GH. Hepatoprotective activity of Silybum marianum and Ci-chorium intybus against thioacetamide in rat. Pak J Nutrition. 2008; 7(1): 172-176.
    64. Madrigal-Santillán E, Madrigal-Bujaidar E, Álvarez-González I, Sumaya-Martínez, M.T, Gutiérrez-Salinas J, Bautista M, Morales-González A, González-Rubio M.G.-L, Leopoldo Aguilar-Faisal, J, Morales-González J.A. Review of natural products with hepato-protective effects. World J Gastroenterol. 2014; 20(40): 14787–14804. 
    65. Maheshwari C, Maryammal R, Venkatanarayanan R. Hepatoprotective activity of orthosiphon stamineus on liver damage caused by Paracetamol in Rats. Jordan J Biol Sci. 2008; 1(3):105-108.
    66. Mama K, Nyunt N, Tin M. The protective effects of Eclipta alba on carbon tetrachloride Induced Acute Liver Damage. Toxicol & Appl Pharmacol. 1978; 45:723-728.
    67. Manjunath BK, Vidya SM. Hepatoprotective Activity of Vitex trifolia against Carbon tetrachloride-induced Hepatic Damage. Ind J Pharma Sci. 2008; 70(2): 241-5.
    68. Manjunatha BK. Hepatoprotective activity of Pterocarpus santalinus L.f, an endangered medicinal plant. Ind J Pharmacol. 2006; 38(1): 25-28.
    69. Mankani KL, Krishna V, Manjunatha BK, Vidya SM, Jagadeesh Singh SD et al. Evaluation of hepatoprotective activity of stem bark of Pterocarpus marsupium Roxb. Ind J Pharmacol. 2005; 37(3):165-168.
    70. Manokaran S, Jaswanth A, Sengottuvelu S, Nandhakumar J, Duraisamy R, Karthikeyan D, Mallegaswari R. Hepatoprotective activity of Aerva lantana Linn. Against Paracetamol induced Hepatotoxicity in Rats. Res J Pharm & Technol. 2008; 1(4): 398-400.
    71. Meena B, Ezhilan RA, Rajesh R, Hussain KS, Ganesan B, Anandan R. Antihepatotoxic potential of Sargassum polycystum (Phaeophyceae) on antioxidant defense status in Dgalactosamine-induced hepatitis in rats. African J Biochem Res. 2008; 2(2): 51-55.
    72. Mehra PN, Nanda SS. Pharmacognosy of Bhringaraja. Antihepatotoxic drug of Indian origin. Ind J Pharm. 1968; 30: 284.
    73. Mohamed AF, Ali HAG, Hamamy MI, Abdel-Sattar E. Antioxident and hepatoprotective effect of Eucalyptus maculate. Med Sci Monit. 2005; 11(11):426-431.
    74. Mohamed STS, Madhusudhana CC, Ramkanth S, Rajan VST, Mahesh KK, Gauthaman K. Hepatoprotective Herbs-A Review. Int J Res Pharm Sci. 2010; 1(1):l-5.
    75. Mohammad N. Qureshi et alIn-vitro Antioxidant and In-vivo Hepatoprotective activity of Leucas ciliate leaves. Rec Nat Prod. 2010: 4, 124-130.
    76. Moongkarndi P, Kosema N, Kaslungka S, Luanratana O, Pongpan N, Neungton N. Antiproliferation, anti-oxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethanopharmacol. 2004; 90: 161–166.
    77. Moron MS, Depierre JW, Mannervik B. Levels of glitathione, glutathione reductase adn glutathione S. trasnferase activities in rat lung and liver. Biochem Biophysics Acta. 1979; 582: 67-78.
    78. Mujeeb M, Aeri V, Bagri P, Khan SA. Hepatoprotective activity of the methanolic extract of Tylophora indica (Burm. f.) Merill. leaves. Int J Green Pharms. 2009; 3(2):125-127.
    79. Mukherjee S, Sur A, Maiti BR. Hepatoprotective effect of Swertia chirata on rat. Indian J Exp Biol. 1997; 35(4): 384-8.
    80. Murugaian P, Ramamurthy V, Karmegam N. Hepatoprotective activity of Wedelia calendulacea L. aainst acute hepatotoxicity in rats. Res J Agri Biol Sci. 2008, 4(6): 685- 687.
    81. Naaz F, Javed S, Abdin M.Z. Hepatoprotective effect of ethanolic extract of Phyllanthus amarus Schum on aflatoxin B1-induced liver damage in mice. J Ethnopharmacol. 2007; 113: 503-509.
    82. Nair DG, Weiskirchen R, Al-Musharafi SK. The use of marine-derived bioactive compounds as potential hepatoprotective agents. Acta Pharmacol Sin. 2015; 36(2): 158–170. 
    83. Nazneen M, Mazid MA, Kundu JK, Bachar SC, Begum F, Datta BK. Protective effects of Flacourtia indica aerial parts extracts against Paracetamol induced hepatotoxicity in rats. J Taibah Uni for Sci. 2009; 2: 1-6.
    84. Niranjan A, Tewari SK, Alok L. Biological activities of Kalmegh(Andrographis paniculataNees). Indian J Nat Prod Resources. 2010; 1(2):125-135.
    85. Nohid T, Agarwal SS. Hepatoprotective activity of Embelia ribes against Paracetamol induced acute hepatocellular damage in mice. JK. Practitioner. 2003; 1091:43-44.
    86. Numazaki, K, Umetsu M, Chiba S. Effect of glycyrrhizin in children with liver dysfunction associated with cytomegalovirus infection. Tohoku J Exp Med. 1994; 172(2): 147-53.
    87. Özbek H, Ugras S, Bayram I, Uygan I, Erdogan E, Öztürk A, Huyut Z. Hepatoprotective effect of Foeniculum vulgare essential oil: A carbon-tetrachloride induced liver fibrosis model in rats. J Lab Anim Sci. 2004; 1: 3.
    88. Özcan M, Akgül A, Baser KHC, Özok T, Tabanca N. Essential oil composition of sea fennel (Crithmum maritimum) from Turkey. Nahrung Food. 2001; 45(5): 353-6.
    89. Padma VV, Suja V, Shyamala DCS, Prema. Hepatoprotective effect of Liv-52 on antitubercular drug induced hepatotoxicity in rats. Fitoterapia. 1998; 69(6): 520-22.
    90. 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(2):121-128.
    91. Pedraza-Chaverri J, Cárdenas-Rodríguez N, Orozco-Ibarra M, Perez-Rojas JM. Medicinal properties of mangos teen (Garcinia mangostana). J Food Toxicol. 2004; 3: 24-27.
    92. Phaneendra P, Kumar MR, Bodhanapu S, Rahaman F. Tamizmani OMT. Hepatoprotective herbs: an overview. Int J Pharm Res develop. 2011; 3(3): 105-111.
    93. Pramyothin P, Samosorn P, Poungshompoo S, Chaichantipyuth C. The protective effects of Phyllanthus emblica Linn. Extract on ethanol induced rat hepatic injury. J Ethnopharmacol. 2006; 107(3): 361-64.
    94. Raj DS, Vennila JJ, Aiyavu C. Panneerselvam K. The hepatoprotective effect of alcoholic extract of Annona squamosa leaves on experimentally induced liver in-jury in Swiss albino mice. Int J Int Bio. 2009; 5(3):162-166.
    95. Ramachandra SS, Absar AQ, Viswanath SAHM, Tushar P, Prakash T, Prabhu K et al. Hepato-protective activity of Calotropis procera flowers against Paracetamol-induced hepatic injury in rats. Fitoterapia. 2007; 78(7-8):451-454.
    96. Rao K.S, Mishra S.H, Hepatoprotective activity of the whole plants of Fumaria indica. Ind J Pharm Sci. 59:1997: 165-70.
    97. Rosa MP and Gutiérrez, Rosario VS. Hepatoprotective and inhibition of oxidative stress of Prostechea michuacana. Rec Nat Prod. 2009; 3(1): 46-51.
    98. Rouf R, Ghosh P, Uzzaman M.R, Sarker D.K, Zahura F.T, Uddin SJ, Muhammad I. Hepatoprotective Plants from Bangladesh: A Biophytochemical Review and Future Prospect. Evid Based Complement Alternat Med. 2021; 2021: 1633231. 
    99. Saleem MTS, Christina AJM, Chidambaranathan N, Ravi V and Gauthaman K. Hepatoprotective activity of Annona squamosa (Linn) on experimental animal model. Int J Appl Res Nat Pro. 2008; 1(3):1-7.
    100. Sandhir R, Gill KD. Hepatoprotective effects of Liv-52 on ethanol induced liver damage in rats. Ind. J Expt Biol. 1999; 37:762-66.
    101. Sanjay J, Dixit VK, Malviya N, Ambawatia V. Antioxident and hepatoprotective activity of ethanolic and aqouaes extract of Amorphophallus companulatus Roxb. Acta Pol Pharma. 2009; 66(4):423-428.
    102. Sanwa Kagaku Kenkyusha Co. Ltd.: Marmen Pharmaceutical Co. Ltd.-Japanese patent. Chem Abst. 102: 32261b, 1985.
    103. Saraswat B, Visen PKS, Dayal R, Agarwal DP, Patnaik GK. Protective action of ursolic acid against chemical induced hepatotoxicity in rats. Ind J Pharmacol. 1996; 28: 232-39.
    104. Saxena S, Sharma R, Rajore S, Batra A. Isolation and identification of flavonoid. Vitexin. from Jatropha curcas L. J Pl Sci Res. 2005; 21:116.
    105. Selvam R, Subramanian L, Gayathri R, Angayarkanni N. The antioxidant activity of turmeric (Curcuma longa). J Ethnopharmacol, 1995; 47:59-67.
    106. Senthilkumar N, Badami S, Dongre S.H, Bhojraj S. Antioxidant and hepatoprotective activity of the methanol extract of Careya arborea bark in Ehrlich ascites carcinoma-bearing mice. J Ethnopharmacol. 2008; 116: 1-6.
    107. Shamsi-Baghbanan H, Sharifian A, Esmaeili S, Minaei B. Hepatoprotective Herbs, Avicenna Viewpoint. Iran. Red. Crescent Med J. 2014; 16(1): e12313.
    108. Shirish S. Pingale Hatoprotection by fresh juice of Leucas Aspera leaves. Der Pharmacia Sinica. 2010; 1: 136-140.
    109. Shirwaiker A, Sreenivasan KK, Krishnanand BR, Kumar AV. Chemical investigation and anti-hepatotoxic activity of the root bark of Caparis spinosa. Fitoterapia. 1996; 67(3): 200-4.
    110. Sidana J, Deswal G, Nain P, Arora K. Liver toxicity and hepatoprotective herbs. Inter J Pharm Sci Rev Res. 2011, 9(1), 116-121.
    111. Simándi B, Deák A, Rónyani E, Yanxiang G, Veress T, Lemberkovics È, Then M, Sass-Kiss Á, Vámos- Falusi Z. Supercritical carbon dioxide extraction and fractionation of Fennel oil. J Agric Food Chem. 1999; 47:1635-40.
    112. Singanan V, Singanan M, Begum H. Hepatoprotective effect of bael leaves (aegle marmelos) in alcohol induced liver injury in albino rats. Inter J Sci Technol. 2007; 2: 83-92.
    113. Somchit MN, Sulaiman MR, Noratunlina R, Ahmad Z. Hepatoprotective effects of Curcuma longa rhizomes in Paracetamol-induced liver damage in rats, Proceedings of the Regional Symposium on Environment and Natural Resources. 2002; 1: 698-702.
    114. Sree Rama Murthy M, Srinivasan M. Hepatotprotective Effect of Tephrosia pupurea in experimental animals. Ind J Pharmacol. 1993; 25:34-36.
    115. Srinivas L, Shalini VK. DNA damage by smoke: Protection by turmeric and other inhibitors of ROS. Free Radical Biol Med. 1991; 11:277-283.
    116. Stickel F, Schuppan D. Herbal medicine in the treatment of liver diseases. Digestive & Liver Disease. 2007; 39: 293–304.
    117. Sultana S, Perwaiz S, Iqbal M, Athar M. Crude extracts of hepatoprotective plants, Solanum nigrum and Ci-chorium intybus inhibit free radical-mediated DNA damage. J Ethnopharmacol. 1995; 45: 189-192.
    118. Suresh KSV, Mishra SH. Hepato protective activity of Baliospermum montanum (Wild) Muell-ARg in rats treated with CCl4: In viva and in vitro studies. PhCog Mag. 2009; 19(5): 196-202.
    119. Tabassum N, Agarwal SS. Hepatoprotective activity of Eclipta alba hassk. against Paracetamol induced hepatocellular damage in mice. Exp Med. 2004; 11(4).
    120. Tabeshpour J, Hosseinzadeh H, Hashemzaei, M, Karimi G. A review of the hepato-protective effects of hesperidin, a flavanon glycoside in citrusfruits, against natural and chemical toxicities. Daru. 2020; 28(1): 305–317. 
    121. Takate SB, Pokharkar RD, Chopade VV, Gite VN. Hepatoprotective activity of ethyl acetate extract of Launaea intybacea in Paracetamol inuced hepatotoxicity in Albino rat. Inter J Pharm Sci Rev Res. 2010; 1(2):72-74.
    122. Thabrew MI, Babaunmi EA. Levels of microsomal drug metabolizing enzymes in animals which are highly susceptible to aflatoxin carcinogenicity: case of duck. Cancer Lett. 1980; 9(4): 333-8.
    123. Thyagarajan SP, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi MS. Herbal medicines for liver diseases in India. J Gastroenterol Hepatol. 2002; 17(3): 370-376.
    124. Thyagarajan SP, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Ms Sripathi et al. Herbal medicine for liver diseases. India J Gastroenterol Hepatol. 2002; 39: 293-304.
    125. Tripathi KD. Essential of Medical Pharmacology. 6th ed. Jaypee brother’s medical publishers, 2008.
    126. Vadivu R, Krithika A, Biplab C, Dedeepya P, Shoeb N, Lakshmi KS. Evaluation of hepatoprotective activity of the fruits of Coccinia grandis Linn. Int J Health Res. 2008; 1(3): 163-168.
    127. Wahid AM, Vijay R Salunkhe, Satish B Bhise. Hepatoprotective activity of hydroalcohalic extract o leaves of Alcocasia indica (Linn). Ind J Exper Biol. 2008; 47:816-821.
    128. Wang M.Y, Anderson G, Nowicki D, Jensen J. Hepatic protection by noni fruit juice against CCl(4)-induced chronic liver damage in female SD rats. Plant Foods Hum Nut. 2008; 63: 141- 145.
    129. Warrier PK, Nambiar VPK, Ramankutty C. Foeniculum vulgare, Indian Medical Plants, Chennai,1996: 492.
    130. Zimmerman MD, Hayman J. Function and integrity of the liver, In: Clinical diagnosis and management by laboratory methods In: Clinical diagnosis and management by laboratory methods, 17th Ed. 1976; 217-50.