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毛蕊异黄酮-7-O-β-D-葡萄糖苷通过激活 AMPK 减轻肝细胞中棕榈酸诱导的脂质堆积。

Calycosin-7-O-β-D-glucoside attenuates palmitate-induced lipid accumulation in hepatocytes through AMPK activation.

机构信息

Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200120, China.

出版信息

Eur J Pharmacol. 2022 Jun 15;925:174988. doi: 10.1016/j.ejphar.2022.174988. Epub 2022 Apr 29.

Abstract

Calycosin-7-O-β-D-glucoside (CG) is the major component of Astragali Radix (AR), a traditional Chinese drug. As reported, CG could attenuate cerebral ischemia/reperfusion injury, protect blood-brain barrier integrity, and ameliorate myocardial infarction. To date, whether CG has a protective effect on metabolic diseases remains to be elucidated. In the present study, CG could attenuate palmitate-induced lipid accumulation in hepatocytes in a dose-dependent manner, with down-regulation of lipogenesis related genes expression and up-regulation of lipids β-oxidation related genes expression. CG could decrease the triglyceride (TG) content from 0.30 mmol/g protein to 0.21 mmol/g protein and reduce the total cholesterol (TC) content from 0.39 mmol/g protein to 0.26 mmol/g protein. Moreover, CG stimulated the phosphorylation of AMP-activated protein kinase (AMPK), and the protective effect of CG on hepatocytes was partially reversed both by the inhibitor of AMPK signaling pathway and overexpression of AMPK-DN. Our findings revealed that CG could ameliorate palmitate-induced lipids accumulation in hepatocytes via AMPK activation and it may be a promising therapeutic medicine for hepatic steatosis.

摘要

毛蕊异黄酮-7-O-β-D-葡萄糖苷(CG)是中药黄芪(AR)的主要成分。据报道,CG 可减轻脑缺血/再灌注损伤,保护血脑屏障完整性,改善心肌梗死。迄今为止,CG 是否对代谢性疾病有保护作用仍有待阐明。在本研究中,CG 可呈剂量依赖性减轻棕榈酸诱导的肝细胞脂质堆积,下调脂生成相关基因的表达,上调脂质β-氧化相关基因的表达。CG 可使三酰甘油(TG)含量从 0.30mmol/g 蛋白降低至 0.21mmol/g 蛋白,总胆固醇(TC)含量从 0.39mmol/g 蛋白降低至 0.26mmol/g 蛋白。此外,CG 刺激 AMP 激活蛋白激酶(AMPK)的磷酸化,AMPK 信号通路抑制剂和 AMPK-DN 的过表达部分逆转了 CG 对肝细胞的保护作用。我们的研究结果表明,CG 通过激活 AMPK 可改善棕榈酸诱导的肝细胞脂质堆积,可能是治疗肝脂肪变性的有前途的药物。

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