PROTECTIVE EFFECT OF KADUKKAI MAATHIRAI (TERMINALIA CHEBULA-BASED POLYHERBAL SIDDHA FORMULATION) IN ETHANOL-INDUCED LIVER DISEASE IN RATS

Manjunath Shetty; Smita Shenoy; Vasudha Devi; Nitesh Kumar; Arul Amuthan; Ganesh Shenoy K; Pavithra P

doi:10.22159/ajpcr.2018.v11i11.26773

Authors

Manjunath Shetty Department of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Smita Shenoy Department of Pharmacology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Vasudha Devi Department of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Nitesh Kumar Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Arul Amuthan Department of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Ganesh Shenoy K Department of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Pavithra P Department of Pathology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i11.26773

Keywords:

Kadukkai maathirai, Hepatoprotective effect, Microvesicular steatosis, Liver enzymes, Siddha

Abstract

Objective: The objective of this study was to evaluate the prophylactic effect of Kadukkai maathirai (KM) against ethanol-induced hepatotoxicity in rats.

Methods: Four groups (n=6) of adult female Spragueâ€“Dawley rats were used. Ethanol was administered in the dose of 45% v/v 15 mL/kg/body weight twice a day for 8 weeks in the study. The four groups were treated orally for 8 weeks with 2% gum acacia (control), ethanol (toxic control), ethanol + KM 72 mg/kg, and ethanol + KM 400 mg/kg, respectively. At the end of 8 weeks, blood was collected by a retro-orbital puncture for the estimation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). The liver was dissected out for histopathology. Using one-way ANOVA and post hoc Tukey's test, the data were analyzed.

Results: There was a significant (p<0.05) decrease in the serum AST and ALT level in rats treated with KM 72 mg/kg as compared to toxic control. Liver parenchyma showed near normal architecture in KM 72 mg/kg-treated group as compared to ethanol-treated group which showed extensive ballooning degeneration of hepatocytes and microvesicular steatosis.

Conclusion: KM, in the dose of 72 mg/kg, which is the therapeutic dosage described in Siddha additional literature, exerted hepatoprotective effect against ethanol-induced liver damage in rats.

Downloads

Download data is not yet available.

References

Wood NJ. Liver: Nonobese individuals in the developing world are at risk of nonalcoholic fatty liver and liver disease. Nat Rev Gastroenterol Hepatol 2010;7:357.

Lazerow SK, Abdi MS, Lewis JH. Drug-induced liver disease 2004. Curr Opin Gastroenterol 2005;21;283-92.

Baig NA, Herrine SK, Rubin R. Liver disease and diabetes mellitus. Clin Lab Med 2001;21:193-207.

Orman ES, Odena G, Bataller R. Alcoholic liver disease: Pathogenesis, management, and novel targets for therapy. J Gastroenterol Hepatol 2013;28:77-84.

Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: From genes toenvironment. Nat Rev Cancer 2006;6:674-87.

Soderberg C, StÃ¥l P, Askling J, Glaumann H, Lindberg G, Marmur J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology 2010;51:595-602.

Yatsuji S, Hashimoto E, Tobari M, Taniai M, Tokushige K, Shiratori K. Clinical features and outcomes of cirrhosis due to non-alcoholic steato hepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol 2009;24:248-54.

Lefkowitch JH. Morphology of alcoholic liver disease. Clin Liver Dis 2005;9:37-53.

Mendez-Sanchez N, Meda-Valdes P, Uribe M. Alcoholic liver disease. An update. Ann Hepatol 2005;4:32-42.

Arteel GE. Oxidants and antioxidants in alcohol-induced liver disease. Gastroenterology 2003;124:778-90.

Cunningham CC, Bailey SM. Ethanol consumption and liver mitochondria function. Biol Signals Recept 2001;10:271-82.

Hoek JB, Pastorino JG. Ethanol, oxidative stress, and cytokine-induced liver cell injury. Alcohol 2002;27:63-8.

Reynolds TB, Benhamou JP, Blake J, Naccarato R, Orrego H. Treatment of alcoholic hepatitis. Gastroenterol Int 1989;2:208-16.

Imperiale TF, McCullough AJ. Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials. Ann Intern Med 1990;113:299-307.

Oâ€™Shea RS, Darasathy S, McCullough AJ. AASLD practice guidelines. Alcoholic liver disease. Hepatology 2010;51:307-28.

Negi AS, Kumar J, Luqman S, Shanker K, Gupta M, Khanuja S. Recent advances in plant hepatoprotectives: A chemical and biological profile of some important leads. Med Res Rev 2008;28:746-72.

Amir M, Mallick M, Ahmad N, Ali A, Ahmad S, Akhtar M, et al. Hepatoprotective effects of Punica granatum fruit against d-galactosamine induced hepatotoxicity in rats: In vitro and in vivo studies. Int J Pharm Pharm Sci 2017;9:168-72.

Salama R, Mohamed M, AbdElwahab M, Shakweer M. Assessment effect of Aloe vera, Azadirachta indica and Moringa oleifera aqueous extracts on carbon tetrachloride-induced hepatotoxicity in rats. Int J Pharm Pharm Sci 2016;8:83-9.

Velayudam, Amuthan A, Ilavarasan. Hepatoprotective activity of Kadukkai Maathirai (A siddha polyherbal formulation) against carbon tetrachloride induced liver damage in rat. Res J Pharm Sci 2012;1:17-21.

SKM Siddha and Ayurveda Company. Therapeutic Index Siddha (Hospital Pharmacopoeia). 1st ed. India: SKM Siddha and Ayurveda Company; 2010. p. 166-7.

Velayudam, Ilavarasan, Amuthan A. Physico-chemical evaluation of kadukkai maathirai and its tablet formulation, a siddha iron preparation used in anemia. Int J Pharmacol Clin Sci 2012;1:3-8.

Tasduq SA, Singh K, Satti NK, Gupta DK, Suri KA. Terminalia chebula (fruit) prevents liver toxicity caused by sub-chronic administration of rifampicin, isoniazid and pyrazinamide in combination. Hum Exp Toxicol 2006;25:111-8.

Nirwane AM, Bapat AR. Effect of methanolic extract of Piper nigrum fruit in ethanhol-CCl4induced hepatotoxicity in wistar rats. Pharm Lett 2012;4:795-802.

Bai X, Zhang W, Chen W, Zong W, Guo Z, Liu X. Anti-hepatotoxic and antioxidant effects of extracts from Piper nigrum L. root. Afr J Biotechnol 2011;10:267-72.

Bhavsar SK, Joshi P, Shah MB, Santani DD. Investigation into hepatoprotective activity of Citrus limon. J Pharm Biol 2007;45:303-11.

Saxena AK, Singh B, Anand KK. Hepatoprotective effects of Eclipta alba on subcellular levels in rats. J Ethnopharmacol 1993;40:156-61.

Thirumalai T, David E, Therasa SV, Elumalai EK. Restorative effect of Eclipta alba in CCl4 induced hepatotoxicity in male albino rats. Asian Pac J Trop Dis 2011;1:304-7.

Malloy HT, Evelyn KA. The determination of bilirubin with the photometric colorimeter, J Biol Chem, 1937;119:481-90.

Singal AK, Anand BS. Recent trends in the epidemiology of alcoholic liver disease. Clin Liver Dis 2013;2:53-6.

Leo MA, Arai M. Hepatotoxicity of vitamin A and ethanol in the rat. Gastroenterology 1982;82:194-205.

Tilg H, Moschen AR, Kaneider NC. Pathways of liver injury in alcoholic liver disease. J Hepatol 2011;55:1159-61.

Hoyt LR, Randall MJ, Ather JL, DePuccio DP, Landry CC, Qian X, et al. Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome. Redox Biol 2017;12:883-96.

Zhou Z, Wang L, Song Z, Lambert JC, McClain CJ, Kang YJ. A critical involvement of oxidative stress in acute alcohol-induced hepatic TNF-alpha production. Am J Pathol 2003;163:1137-46.

Thurman RG. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. Am J Physiol 1998;275:605-11.

Tsukamoto H, Takei Y, McClain CJ, Shimizu H, Sato N, Thurman R. How is the liver primed or sensitized for alcoholic liver disease. Alcohol Clin Express Res 2001;25:171-81.

Dabba MH, Abdel-Rahman MS. Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. Toxicol Lett 1998;95:23-9.

Jaiswal SK, Gupta VK, Siddiqi NJ, Pandey RS, Sharma B. Hepatoprotective effect of Citrus limon fruit extract against carbofuran induced toxicity in wistar rats. Chinese J Biol 2015;13:1-11.

Vijayakumar RS, Surya D, Nalini N. Antioxidant efficacy of black pepper (Piper nigrum L.) andpiperine in rats with high fat diet induced oxidative stress. Redox Rep 2004;9:105-10.

Selvendiran K, Sakthisekaran D. Chemopreventive effect of piperine on modulating lipid peroxidation and membrane bound enzymes in benzo (a) pyrene induced lung carcinogenesis. Biomed Pharmacother 2004;58:264-7.

Juang LJ, Sheu SJ, Lin TC. Determination of hydrolyzable tannins in the fruit of Terminalia chebula Retz. by high-performance liquid chromatography and capillary electrophoresis. J Sep Sci 2004;27:718-24.

Panunto W, Jaijoy K, Lerdvuthisopon N, Lertprasertsuke N, Jiruntanat N, Soonthornchareonnon N, et al. Acute and chronic toxicity studies of the water extract from dried fruits of Terminalia chebula Rezt. in rats. Int J Appl Res Nat Prod 2010;3:36-43.

Pfundstein B, El Desouky SK, Hull WE, Haubner R, Erben G, Owen RW. Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): Characterization, quantitation and determination of antioxidant capacities. Phytochemistry 2010;71:1132-48.

Lee HS, Jung SH, Yun BS, Lee KW. Isolation of chebulic acid from Terminalia chebula Retz. and its antioxidant effect in isolated rat hepatocytes. Arch Toxicol 2007;81:211-8.

Lee SI, Hyun PM, Kim SH, Kim KS, Lee SK, Kim BS, et al. Suppression of the onset and progression of collagen induced arthritis by chebulagic acid screened from a natural product library. Arthritis Rheum 2005;52:345-53.

Wagner H, Geyer B, Kiso Y, Hikino H, Rao GS. Coumestans as the main active principles of the liver drugs Eclipta alba and Wedelia calendulacea. Planta Med 1986;5:370-4.