The protective effect of hyperoside on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2

Hyperoside was used to treat cardiovascular disease for many years in China. It was shown great effect on regulation of lipid metabolism. But there is lack of reports about the effects of hyperoside on liver diseases. This study was designed to investigate the potentially protective effects of hyperoside and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation on Carbon Tetrachloride (CCl4)-induced chronic liver fibrosis in mice. All mice were divided into six groups containing 6 animals per group. Mice in different group were given relative processing for 4 weeks. The potentially protective effects of hyperoside on CCl4-induced chronic liver fibrosis in mice were depicted histologically and biochemically. CCl4 administration caused a marked increase in the levels of serum aminotransferases, serum monoamine oxidase (MAO) and lipid peroxidation, MAO in mouse liver homogenates. Also decreased activities of cellular antioxidant defense enzymes were found after CCl4 exposure. Histopathological changes induced by CCl4 including regenerative nodules, deteriorated parenchyma. Hyperoside and silymarin reduced these changes and attenuated the pathological effects of CCl4 induced liver injury. In addition, hyperoside exhibited antioxidant effects in vitro. In Western blot analysis, the protein level of Nrf2 was downregulated after CCl4 administration and reversed by hyperoside. Hyperoside increased the activity of the antioxidant and phase II detoxifying enzymes through the activation of Nrf2 nuclear translocated in the CCl4-induced liver fibrosis mice.