Objective: To investigate the protective effect of berberine (BBR) on liver damage under high-cholesterol diet challenge. Methods: Eight-week old male C57BL/6J mice were randomly divided into normal diet group, high cholesterol diet (1.25% cholesterol+0.5% cholic acid) group and high cholesterol diet+BBR (100 mg/kg per day by gavage) group, with 10 mice in each group. Liver and serum plasma samples were collected after 8-week feeding. Hepatic mRNA expressions of genes involved in endoplasmic reticulum stress (ER stress), oxidative stress and inflammatory cytokines were determined by real-time quantitative PCR, and content of malondialdehyde (MDA) in liver tissues was measured. HepG2 cell line was used to investigate the effect of BBR on ER stress under high cholesterol challenge. Results: Compared with normal diet group, hepatic mRNA expressions of genes in ER stress, oxidative stress and inflammatory cytokines increased significantly in high cholesterol diet group (P<0.05), and were reduced closely to levels of normal diet group by BBR treatment (P<0.05). BBR also down-regulated the increased hepatic MDA content induced by high cholesterol diet (P<0.05). Furthermore, BBR decreased the expression of GRP78, a key protein marker concerning ER stress (P<0.05), as well as the fluorescence intensity of DHE probe after high cholesterol treatment in HepG2 cells. Conclusions: BBR could effectively ameliorate hepatic ER stress, oxidative stress and inflammatory response under high cholesterol challenge, which might protect liver from damage when overloaded with cholesterol.
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