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Chrysin prevents inflammation-coinciding liver steatosis via AMPK signalling

作者:Chuanyue Gao, Huan Zhang, Lulin Nie, Kaiwu He, Peimao Li, Xingxing Wang, Zaijun Zhang, Yongmei Xie, Shupeng Li, Gong‐Ping Liu, Xinfeng Huang, Huiping Deng, Jianjun Liu, Xifei Yang · 发表于:Journal of Pharmacy and Pharmacology · 年份:2023 · DOI:10.1093/jpp/rgad041 · 被引用次数:13 · 研究领域:Flavonoids in Medical Research、Liver Disease Diagnosis and Treatment、Metabolism, Diabetes, and Cancer

OBJECTIVES: We aimed to elucidate the therapeutic potential of Chrysin (CN) against the high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) and its mechanism. METHODS: To assess the hypothesis, NAFLD was induced in C57BL/6 mice by feeding a high-fat diet for up to two months, followed by CN administration (for three months). Liver injury/toxicity, lipid deposition, inflammation and fibrosis were detected via molecular and biochemical analysis, including blood chemistry, immunoimaging and immunoblotting. Moreover, we performed proteomic analysis to illuminate Chrysin's therapeutic effects further. KEY FINDINGS: CN treatment significantly reduced liver-fat accumulation and inflammation, ultimately improving obesity and liver injury in NAFLD mice. Proteomic analysis showed that CN modified the protein expression profiles in the liver, particularly improving the expression of proteins related to energy, metabolism and inflammation. Mechanistically, CN treatment increased AMP-activated protein and phosphorylated CoA (P-ACC). Concurrently, it reduced inflammation and inflammation activation by inhibiting NLRP3 expression. CONCLUSIONS: In summary, CN treatment reduced lipid metabolism by AMPK and inflammasome activation by NLRP3 inhibition, ultimately improving NAFLD progression. These findings suggest that CN could be a potential treatment candidate for the NFLAD condition.