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