Background

Asperosaponin VI (AVI) is a natural triterpenoid saponin isolated from Dipsacus asper Wall with documented anti-inflammatory and bone protective effects. Our previous work reported that AVI protects the liver of septic mice from acute inflammatory damage. In this paper, we further explored the protective effect and the potential mechanisms of AVI in alcoholic fatty liver disease (AFLD).

Methods

The Lieber-Decarli model was constructed to evaluate the effect of AVI on AFLD in C57BL/6 J mice. Additional in vitro work was performed to investigate HepG2 cells exposed to alcohol, then analyzed the degree of liver injury by detecting the ALT and AST levels both in the liver and serum. H&E staining and Sirius red staining were used to evaluate the histopathology variations in the liver. Further, observe lipid droplets in the cytoplasm by Oil Red O staining. We detected the expression of inflammatory cytokines with qualitative PCR; ROS, MDA, SOD, and GSH-px levels were analyzed to observe oxidative stress. Finally, exploring the activation of AMPK signaling pathway by real-time PCR and Western blotting.

Results

Histological examination of liver tissue combined with serum ALT and AST levels showed a significant protective effect of AVI against alcoholic liver injury in AFLD mice. Compared with the model group, AVI evidently improved antioxidant capacity, reduced inflammatory response and lipid accumulation both in vitro and in vivo. For mechanically, it was found that AVI up-regulated phosphorylation level of AMP-activated protein kinase (AMPK) and inhibited the endoplasmic reticulum stress (ER) pathway in AFLD.

Conclusion

AVI protects mice from alcohol-induced hepatic steatosis and liver injury through activating AMPK signaling and repress ER stress, suggesting that it might be a potential therapeutic agent for AFLD.

中文翻译：

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Asperosaponin VI 通过调节脂质代谢和 ER 应激来保护酒精诱导的肝脂肪变性和损伤

背景

Asperosaponin VI (AVI) 是一种从续断中分离出来的天然三萜皂苷，具有抗炎和骨骼保护作用。我们之前的工作报道了 AVI 可以保护脓毒症小鼠的肝脏免受急性炎症损伤。在本文中，我们进一步探讨了AVI对酒精性脂肪性肝病（AFLD）的保护作用和潜在机制。

方法

构建Lieber-Decarli模型来评估AVI对C57BL/6 J小鼠AFLD的影响。还进行了额外的体外工作来研究暴露于酒精的 HepG2 细胞，然后通过检测肝脏和血清中的 ALT 和 AST 水平来分析肝损伤的程度。H&E染色和天狼星红染色用于评估肝脏的组织病理学变化。此外，通过油红O染色观察细胞质中的脂滴。我们通过定性PCR检测炎症细胞因子的表达；分析 ROS、MDA、SOD 和 GSH-px 水平以观察氧化应激。最后，通过实时PCR和Western blotting探索AMPK信号通路的激活。

结果

肝组织组织学检查结合血清ALT和AST水平显示AVI对AFLD小鼠酒精性肝损伤具有显着的保护作用。与模型组相比，AVI在体外和体内均明显提高抗氧化能力，减少炎症反应和脂质积累。机械方面，发现 AVI 上调 AMP 激活蛋白激酶 (AMPK) 的磷酸化水平并抑制 AFLD 中的内质网应激 (ER) 通路。

结论

AVI 通过激活 AMPK 信号传导和抑制 ER 应激来保护小鼠免受酒精诱导的肝脂肪变性和肝损伤，这表明它可能是 AFLD 的潜在治疗剂。