School of Pharmacy, Jinan University, Guangzhou, 510632, China.
YZ Health-Tech Inc., Hengqin District, Zhuhai, 519000, China.
Sci Rep. 2022 Jul 27;12(1):12857. doi: 10.1038/s41598-022-16119-0.
Isosteviol sodium (STVNa) is a beyerane diterpene synthesized via acid hydrolysis of stevioside, which can improve glucose and lipid metabolism in animals with diabetes. However, it remains unknown whether STVNa can exhibit a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. We hypothesize that autophagic initiation may play a key role in mediating the development of NAFLD. Herein, we assessed the effects of STVNa on NAFLD and its underlying mechanisms. The results demonstrated that STVNa treatment effectively ameliorated NAFLD in rats fed high-fat diet (HFD). Moreover, STVNa decreased the expression of inflammation-related genes and maintained a balance of pro-inflammatory cytokines in NAFLD rats. STVNa also reduced lipid accumulation in free fatty acid (FFA)-exposed LO2 cells. In addition, STVNa attenuated hepatic oxidative stress and fibrosis in NAFLD rats. Furthermore, STVNa enhanced autophagy and activated Sirtuin 1/adenosine monophosphate-activated protein kinase (Sirt1/AMPK) pathway both in vivo and in vitro, thus attenuating intracellular lipid accumulation. In summary, STVNa could improve lipid metabolism in NAFLD by initiating autophagy via Sirt1/AMPK pathway. Therefore, STVNa may be an alternative therapeutic agent for treatment of NAFLD.
异甜菊醇钠（STVNa）是通过甜菊糖苷的酸水解合成的贝壳杉二萜，可改善糖尿病动物的葡萄糖和脂质代谢。然而，STVNa 是否对非酒精性脂肪性肝病（NAFLD）具有治疗作用及其潜在机制尚不清楚。我们假设自噬起始可能在介导 NAFLD 的发展中起关键作用。在此，我们评估了 STVNa 对 NAFLD 及其潜在机制的影响。结果表明，STVNa 治疗可有效改善高脂肪饮食（HFD）喂养的大鼠的 NAFLD。此外，STVNa 降低了炎症相关基因的表达，并维持了 NAFLD 大鼠促炎细胞因子的平衡。STVNa 还减少了游离脂肪酸（FFA）暴露的 LO2 细胞中的脂质积累。此外，STVNa 减轻了 NAFLD 大鼠的肝氧化应激和纤维化。此外，STVNa 增强了自噬，并在体内和体外激活了沉默信息调节因子 1/腺苷单磷酸激活蛋白激酶（Sirt1/AMPK）通路，从而减轻了细胞内脂质积累。综上所述，STVNa 可通过 Sirt1/AMPK 通路诱导自噬来改善 NAFLD 中的脂质代谢。因此，STVNa 可能是治疗 NAFLD 的一种替代治疗剂。
