Potent effects of dioscin against thioacetamide-induced liver fibrosis through attenuating oxidative stress in turn inhibiting inflammation, TGF-β/Smad and MAPK signaling pathways. (June 2015)

• Record Type: Journal Article
• Authors: Zhang, Xiaoling; Xu, Youwei; Qi, Yan; Han, Xu; Yin, Lianhong; Xu, Lina; Liu, Kexin; Peng, Jinyong
• Is Part Of: Journal of functional foods. Volume 16(2015)
• Page Start: 436
• Page End: 447
• Publication Date: 2015-06
• Subjects: Dioscin -- Hepatoprotective effect -- Hepatic stellate cell -- Liver fibrosis -- Thioacetamide; TAA thioacetamide -- PPAR-γ peroxisome proliferator activated receptor-γ -- α-SMA α-smooth muscle actin -- HSC hepatic stellate cell -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- H&E hematoxylin and eosin -- COL1A1 collagen α1 (I) -- COL3A1 collagen α1 (III) -- TNF-α1 tumor necrosis factor-alpha -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- NF-κB Nuclear Factor-κB -- COX-2 cyclooxygenase-2 -- HMGB-1 high-mobility group box 1 -- MDA malondialdehyde -- GSH glutathione -- Nrf2 NF-E2-related factor 2 -- NQO1 NAD(P)H quinone oxidoreductase 1 -- Mn-SOD manganese superoxide dismutase -- GST glutathione-S-transferase -- HO-1 heme oxygenase-1 -- MMP matrix metalloproteinase -- TIMP tissue inhibitor of matrix metalloproteinases -- MAPK mitogen-activated protein kinase -- TGF-β transforming growth factor-β; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2015.04.052
• Languages: English
• ISSNs: 1756-4646

Abstract

Highlights: Dioscin significantly suppressed the proliferation of HSC-T6 cells. Dioscin showed potent effect against TAA-induced liver fibrosis in rats. Dioscin showed anti-oxidative and anti-inflammatory effects. Dioscin effectively facilitated matrix degradation. Dioscin markedly inhibited TGF-β/Smad and MAPK signaling pathways. Abstract: The protective effects and mechanisms of dioscin against liver fibrosis were investigated. The results showed that dioscin markedly suppressed the proliferation of HSC-T6 cells, but not to the isolated hepatocytes, down-regulated the levels of fibronectin, α-SMA, collagen and vimentin, and up-regulated PPAR-γ expression to inhibit HSC activation. Interestingly, dioscin also significantly rehabilitated the levels of body weights, AST, ALT and hydroxyproline in rats caused by TAA, which were verified by histological determinations. Mechanistically, dioscin obviously facilitated matrix degradation, significantly decreased liver inflammation by inhibiting NF-κB activation and proinflammatory cytokine production, attenuated oxidative stress by reducing lipid peroxidation and activating Nrf2-mediated antioxidantive enzymes, and evidently adjusted TGF-β/smad and MAPK signaling pathways. In conclusion, dioscin ameliorated liver fibrosis via affecting oxidative stress, inflammation, HSC activation, matrix degradation, TGF-β/smad and MAPK pathways, which should be developed to be one effective food and healthcare product for the treatment of liver fibrosis in the future.