Mechanistic Insights into Achyranthes Bidentata Blume Water Extract in Alleviating NAFLD: PPARγ-Driven Synergistic Regulation of Lipid Metabolism and Macrophage Efferocytosis.

IF 2
Xiong Ying Li, Ru Meng Yao, Xiao Ming Zou, Yun Xu, Sha Ying Qiu, Ping Ping He, Li Jun Wang, Shan Shan Lei
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Abstract

Introduction: Achyranthes bidentata Blume (AB), a traditional Chinese medicine, is used to treat Non-alcoholic fatty liver disease (NAFLD), although its precise mechanism of action remains unclear. This study investigated the effects of Achyranthes bidentata water extract (ABW) on NAFLD in mice induced by high-fat-fed.

Methods: The chemical components of Achyranthes bidentata Blume water extract (ABW) were analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). After 12 weeks of ABW treatment, liver histopathology and hepatic lipid levels, including total cholesterol (TC) and triglycerides (TG), were evaluated in NAFLD mice. Enzyme-linked immunosorbent assay, quantitative PCR, western blotting, and immunofluorescence were employed to assess changes in the PPARγ/LXRα signaling pathway and macrophage efferocytosis in vivo and in vitro.

Results: In vivo, ABW treatment significantly reduced hepatic lipid accumulation (TC and TG) and alleviated hepatic lesions compared with the model group. ABW also upregulated genes associated with lipid metabolism and macrophage efferocytosis, while reducing the hepatic levels of inflammatory cytokines and the number of apoptotic cells. In vitro, ABW suppressed the expression of pro-inflammatory genes (Il1b, Il6, Tnf, and Nos2) and enhanced the expression of macrophage efferocytosis-related genes (Pparγ, Gas6, Tyro3, and Axl) in ox-LDL-induced Raw 264.7 cells. UHPLC-MS identified 501 compounds in ABW. Auto-docking analysis suggested that 4-dodecylbenzenesulfonic acid, isovanilic acid, and oleanolic acid are potential PPARγ activators present in ABW.

Discussion: This study demonstrates that ABW ameliorates NAFLD by activating the PPARγ/LXRα signaling pathway and promoting macrophage efferocytosis.

Conclusion: These findings provide a novel mechanistic insight into the therapeutic effects of multi- component herbal medicines for NAFLD.

牛膝水提取物缓解NAFLD的机制:ppar γ驱动的脂质代谢和巨噬细胞Efferocytosis的协同调节。
牛膝(Achyranthes bidentata Blume, AB)是一种中药,用于治疗非酒精性脂肪性肝病(NAFLD),但其确切的作用机制尚不清楚。本研究探讨牛膝水提物(ABW)对高脂喂养小鼠NAFLD的影响。方法:采用超高效液相色谱-质谱联用技术对牛膝水提物(ABW)进行化学成分分析。ABW治疗12周后,评估NAFLD小鼠的肝脏组织病理学和肝脏脂质水平,包括总胆固醇(TC)和甘油三酯(TG)。采用酶联免疫吸附法、定量PCR、免疫印迹法和免疫荧光法检测小鼠体内和体外PPARγ/LXRα信号通路和巨噬细胞efferocytic的变化。结果:在体内,与模型组相比,ABW治疗显著降低了肝脏脂质积累(TC和TG),减轻了肝脏病变。ABW还上调与脂质代谢和巨噬细胞efferocytosis相关的基因,同时降低肝脏炎症细胞因子水平和凋亡细胞数量。在体外实验中,ABW抑制了ox- ldl诱导的Raw 264.7细胞中促炎基因(Il1b、Il6、Tnf和Nos2)的表达,并增强了巨噬细胞efferocysis相关基因(Pparγ、Gas6、Tyro3和Axl)的表达。UHPLC-MS鉴定出ABW中501个化合物。自动对接分析表明,4-十二烷基苯磺酸、异香草酸和齐墩果酸是ABW中潜在的PPARγ激活剂。讨论:本研究表明,ABW通过激活PPARγ/LXRα信号通路和促进巨噬细胞efferocytosis来改善NAFLD。结论:这些发现为多组分中草药治疗NAFLD提供了新的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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