Search

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. [ABSTRACT FROM AUTHOR]

Flavonoids have demonstrated beneficial effects in fatty liver disease (FLD). Consumption of flavonoids is associated with several health benefits via their antioxidant and anti-inflammatory activities. The current study aimed to investigate hesperidin and myricetin as new candidates for FLD therapy. Five-week-old female ICR mice were provided a high fat diet (HFD) 60 kcal % fat of total food and daily intragastrically administered ethanol (0.5 g/kg/day) in combination with fenofibrate (40 mg/kg/day) or flavonoids, hesperidin or myricetin (50 and 200 mg/kg/day), for 60 consecutive days. Hepatic histomorphology was observed with oil red O (ORO) staining along with hepatic triglyceride (TG) level, activity of antioxidative enzymes, and mRNA expression of metabolic, antioxidative, and inflammatory genes, including peroxisome proliferator activated receptor-alpha and -gamma 2 (Ppara and Pparg2), sterol regulatory element binding protein-1c (Srebp-1c), acetyl-CoA carboxylase (Acaca), fatty acid synthase (Fasn), CD36 molecules (Cd36), catalase (Cat), superoxide dismutase 1 and 2 (Sod1 and Sod2), glutathione peroxidase 1 (Gpx1), nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Nfkb1), tumor necrosis factor-alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2). Fenofibrate, hesperidin, and myricetin improved hepatic histomorphology, restored expression of metabolic genes, improved antioxidative system, and suppressed inflammatory pathways. Interestingly, hesperidin attenuated TG level and down-regulated Ccl2 expression at low dose and reinstated Cat expression better than myricetin. These findings confirm that hesperidin is a promising candidate for FLD therapy. [ABSTRACT FROM AUTHOR]