Garcinia mangostana Linn. pericarp and alpha-mangostin ameliorate dextran sulfate sodium-induced hepatic injury in mice.

Abstract

Anti-inflammatory and antioxidant effects of Garcinia mangostana (GM) and α-mangostin (MGS) on dextran sulfate sodium (DSS)-induced hepatotoxicity were examined. Male Institute of Cancer Research (ICR) mice were orally administered GM (40, 200, and 1000 mg/kg/day), MGS (30 mg/kg/day), or sulfasalazine (100 mg/kg/day) for 7 days. Hepatic injury was induced by oral administration of DSS (40 kDa, 6 g/kg/day) on days 4 - 7. Colitis disease activity index (DAI) and serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) were determined on day 7. The livers were removed for histological analysis by hematoxylin and eosin staining, and for determination of myeloperoxidase (MPO) activity, malondialdehyde (MDA) and nitric oxide (NO) levels, and superoxide dismutase (SOD) and catalase (CAT) activities. Expression of inflammatory associated genes, including pro-inflammatory cytokines tumor necrosis factor α (Tnfα) and interleukin 1 beta (Il1β), vascular and intercellular adhesion molecules (Vcam1 and Icam1), chemokine (C-C motif) ligand 2 (Ccl2), nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Nfkb1), nuclear factor erythroid derived 2 like 2 (Nfe2l2), and toll-like receptor 2 and 4 (Tlr2 and Tlr4) were examined by RT-qPCR. DSS-induced hepatic histopathological changes (cell membrane disruption, pyknotic nuclei, and necrotic areas) corresponded with increases in DAI, serum AST and ALT, MPO activity, and MDA and NO levels, and decreases in SOD and CAT activities. GM and MGS prevented DSS-induced hepatic histopathological changes, reduced MPO activity and MDA and NO levels, and enhanced SOD and CAT activities. GM and MGS prevented DSS-induced upregulation of Tnfα, Il1β, Vcam1, Icam1, Ccl2, Nfkb1, and Tlr4. Sulfasalazine did not indicate any improvement. GM and MGS ameliorated DSS-induced hepatotoxicity via suppression of inflammatory and oxidative responses.