Evaluation of protective effect of Sapindus mukorossi saponin fraction on CCl4-induced acute hepatotoxicity in rats

Abstract

M Srinivasa Rao,1 B Syed Asad,1 MA Fazil,1 RD Sudharshan,1 SA Rasheed,1 HA Pradeep,1 S Aboobacker,2 AH Thayyil,1 AK Riyaz,1 M Mansoor,1 MA Aleem,1 K Zeeyauddin,3 M Lakshmi Narasu,4 A Anjum,1,5 M Ibrahim1,51Nizam Institute of Pharmacy, Andhra Pradesh; 2Department of Pharmacology, Jamiya Salafiya College of Pharmacy, Kerala; 3Department of Pharmacology, Deccan School of Pharmacy, Andhra Pradesh; 4Centre for Biotechnology, Jawaharlal Nehru Technological University, Andhra Pradesh; 5Asian Institute of Advanced Scientific and Pharmaceutical Research, Hyderabad, Andhra Pradesh, IndiaAim: This investigation aimed to assess the hepatoprotective effect of saponin fraction isolated from the fruit pericarp of Sapindus mukorossi on carbon tetrachloride (CCl4)-induced hepatotoxicity.Methods: Fruit of S. mukorossi was collected and authenticated, and dried pericarp powder subjected to extraction with cold ethanol (70%) by maceration followed by isolation of total saponin fraction. Hepatoprotective activity was demonstrated in the CCl4-damaged primary monolayer culture. In in vivo studies, pretreatment with total saponin fraction (50,100 and 150 mg/kg per os once a day for 4 days before CCl4 introduction and continued afterward for 3 days) attenuated the CCl4-induced acute increase in serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase activities and considerably reduced histopathological alterations. Further, saponin fraction reduced thiopentone-induced (4 mg/kg, intraperitoneal) sleeping time in rats.Results: Saponin fraction pretreatment improves bromsulphalein clearance and also increases cellular viability. Saponin administration replenished depleted hepatic glutathione and superoxide dismutase by improving the antioxidant status of the liver and liver function enzymes. These effects substantiate protection of cellular phospholipids from peroxidative damage induced by highly reactive toxic intermediate radicals formed during biotransformation of CCl4.Conclusion: The above findings lead to the conclusion that the saponin fraction of S. mukorossi has a protective capability both in vitro on primary hepatocyte cultures and in vivo in a rat model of CCl4-mediated liver injury. Hence, we suggest that the inclusion of this S. mukorossi fruit pericarp in the management of liver disorders is justified.Keywords: Sapindus mukorossi, total saponin content, hepatoprotective