Protection effect of piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats
- 327 Downloads
Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of detoxication, antioxidation, and antimutation. In this study, we evaluated the antihepatotoxic effect of PBL extract on the carbon tetrachloride (CCl4)-induced liver injury in a rat model. Fibrosis and hepatic damage, as reveled by histology and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were induced in rats by an administration of CCl4 (8%, 1 ml/kg body weight) thrice a week for 4 weeks. PBL extract significantly inhibited the elevated AST and ALT activities caused by CCl4 intoxication. It also attenuated total glutathione S-transferase (GST) activity and GST α isoform activity, and on the other hand, enhanced superoxide dismutase (SOD) and catalase (CAT) activities. The histological examination showed the PBL extract protected liver from the damage induced by CCl4 by decreasing α-smooth muscle actin (α-sma) expression, inducing active matrix metalloproteinase-2 (MMP2) expression though Ras/Erk pathway, and inhibiting TIMP2 level that consequently attenuated the fibrosis of liver. The data of this study support a chemopreventive potential of PBL against liver fibrosis.
KeywordsPiper betel leaf Liver fibrosis Glutathione S-transferase α-smooth muscle actin Matrix metalloproteinase-2
This work was supported by the grants from National Science Council (NSC94-2320-B-040-040) and Chung Shan Medical University (CSMC 92-OM-B-002), Taiwan.
- Capdevielle-Pardies P, David J, Miquel JL, Le Bras M (1985) Quid of betel. Med Trop (Mar) 45:299–307Google Scholar
- Hengstler JG, Böttger T, Tanner B, Dietrich B, Henrich M, Knapstein PG, Junginger T, Oesch F (1998) Resistance factors in colon cancer tissue and the adjacent normal colon tissue: glutathione S-transferases C and J, glutathione and aldehyde dehydrogenase. Cancer Lett 128:105–112PubMedCrossRefGoogle Scholar
- Hernandez-Mounoz R, Diaz-Munoz M, Suarez-Cuenca JA, Trejo-Solis C, Lopez V, Sanchez-Sevilla L, Yanez L, De Sanchez VC (2001) Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats. Hepatology 34:677–687CrossRefGoogle Scholar
- Lear JT, Heagerty AHM, Smith A, Bowers B, Payne C, Smith CA, Jones PW, Gilford J, Yengi L, Alldersea J, Fryer AA, Strange RC (1996) Multiple cutaneous basal cell carcinomas: glutathione-S transferase (GSTM1, GSTT1) and cytochrome P-450 (CYP2D6, CYP1A1) polymorphisms influence tumour numbers and accrual. Carcinogenesis 17:1891–1896PubMedCrossRefGoogle Scholar
- Murphy G, Stanton H, Cowell S (1999) Mechanisms for pro matrix metalloproteinase activation. Acta Pathol Microbiol Immunol Scand 1:38–44Google Scholar
- Paquet KJ, Kamphausen U (1975) The carbon-tetrachloride-hepatotoxicity as a model of liver damage. First report Long-time biochemical changes. Acta Hepatogastroenterol 22:84–88Google Scholar
- Roeb E, Bosserhoff AK, Hamacher S, Jansen B, Dahmen J, Wagner S, Matern S (2005) Enhanced migration of tissue inhibitor of metalloproteinase overexpressing hepatoma cells is attributed to gelatinases: relevance to intracellular signaling pathways. World J Gastroenterol 11:1096–1104PubMedGoogle Scholar