芝麻素通过上调法尼醇 X 受体缓解 HFD 诱导的小鼠肝脂质积累。
Schaftoside alleviates HFD-induced hepatic lipid accumulation in mice via upregulating farnesoid X receptor.
机构信息
Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China; School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China; Zhuhai Precision Medicine Center, Zhuhai People's Hospital, Zhuhai, 519000, China.
出版信息
J Ethnopharmacol. 2020 Jun 12;255:112776. doi: 10.1016/j.jep.2020.112776. Epub 2020 Mar 20.
ETHNOPHARMACOLOGY RELEVANCE
The farnesoid X receptor (FXR) is a therapeutic target of for the treatment of non-alcoholic fatty liver disease (NAFLD) owing to its regulatory role in lipid homeostasis. Schaftoside (SS) is a bioactive compound of Herba Desmodii Styracifolii, which has traditionally been used to treat hepatitis and cholelithiasis. However, the potential hepatoprotective effect of SS against NAFLD and the underlying mechanisms remain unknown.
AIM OF THE STUDY
We investigated whether SS could improve NAFLD-induced liver injury by decreasing lipid accumulation via the activation of FXR signalling.
MATERIALS AND METHODS
In vivo, the effects of SS on high-fat diet (HFD)-induced lipid accumulation in the liver of mice were evaluated by serum biochemical parameters and histopathological analysis. In vitro, the intracellular triglyceride (TG) level and Oil Red O staining were used to evaluate the lipid removal ability of SS in Huh-7 cells or FXR knockout mouse primary hepatocytes (MPHs) induced by oleic acid (OA). Moreover, FXR/sterol regulatory element-binding protein 1 (SREBP1) mRNA and protein expression levels were detected.
RESULTS
SS reduced HFD-induced lipid accumulation in the liver, as indicated by decreased aspartate aminotransferase (AST), cholesterol (Ch), and TG levels in serum and TG levels in liver tissue, and subsequently resulting in attenuation of liver histopathological injury. Gene expression profiles demonstrated that SS dose-dependently prevented HFD-induced decrease of FXR expression and inversely inhibited SREBP1 expression in the nucleus. Furthermore, SS significantly suppressed excessive TG accumulation and decreased intracellular TG level in Huh-7 cells or MPHs via the upregulation of FXR and inhibition of SREBP1 expression in the nucleus.
CONCLUSION
Our results suggest that SS ameliorates HFD-induced NAFLD by the decrease of lipid accumulation via the control of FXR-SREBP1 signalling.
草药舞草治疗非酒精性脂肪性肝病的活性成分——舞草苷通过激活法尼醇 X 受体抑制肝脏脂质蓄积
摘要： 法尼醇 X 受体 (FXR) 是治疗非酒精性脂肪性肝病 (NAFLD) 的治疗靶点，因为它在脂质动态平衡中起调节作用。舞草苷 (SS) 是舞草的一种生物活性化合物，传统上用于治疗肝炎和胆石症。然而，SS 对 NAFLD 的潜在保肝作用及其潜在机制尚不清楚。
目的：本研究旨在探讨 SS 是否通过激活 FXR 信号通路减少脂质堆积来改善 NAFLD 诱导的肝损伤。
材料与方法：在体内，通过血清生化参数和组织病理学分析评估 SS 对高脂肪饮食 (HFD) 诱导的小鼠肝脏脂质堆积的影响。在体外，用油红 O 染色法检测 SS 在油酸 (OA) 诱导的 Huh-7 细胞或 FXR 敲除小鼠原代肝细胞 (MPHs) 中去除细胞内甘油三酯 (TG) 的能力。此外，还检测了 FXR/固醇调节元件结合蛋白 1 (SREBP1) mRNA 和蛋白表达水平。
结果：SS 降低了 HFD 诱导的肝脏脂质堆积，血清中天冬氨酸氨基转移酶 (AST)、胆固醇 (Ch) 和 TG 水平以及肝组织中的 TG 水平降低，随后肝组织病理损伤减轻。基因表达谱表明，SS 可剂量依赖性地防止 HFD 诱导的 FXR 表达降低，并反式抑制核内 SREBP1 表达。此外，SS 通过上调 FXR 和抑制核内 SREBP1 表达，显著抑制了 Huh-7 细胞或 MPHs 中过多的 TG 积累和细胞内 TG 水平的降低。
结论：我们的研究结果表明，SS 通过控制 FXR-SREBP1 信号通路减少脂质堆积来改善 HFD 诱导的 NAFLD。
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