Xiong Ying Li, Ru Meng Yao, Xiao Ming Zou, Yun Xu, Sha Ying Qiu, Ping Ping He, Li Jun Wang, Shan Shan Lei
{"title":"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。","authors":"Xiong Ying Li, Ru Meng Yao, Xiao Ming Zou, Yun Xu, Sha Ying Qiu, Ping Ping He, Li Jun Wang, Shan Shan Lei","doi":"10.2174/0118715303385546250912094219","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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 <i>Achyranthes bidentata</i> water extract (ABW) on NAFLD in mice induced by high-fat-fed.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. <i>In vitro</i>, ABW suppressed the expression of pro-inflammatory genes (<i>Il1b, Il6, Tnf, and Nos2</i>) and enhanced the expression of macrophage efferocytosis-related genes (<i>Pparγ, Gas6, Tyro3, and Axl</i>) 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.</p><p><strong>Discussion: </strong>This study demonstrates that ABW ameliorates NAFLD by activating the PPARγ/LXRα signaling pathway and promoting macrophage efferocytosis.</p><p><strong>Conclusion: </strong>These findings provide a novel mechanistic insight into the therapeutic effects of multi- component herbal medicines for NAFLD.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mechanistic Insights into <i>Achyranthes Bidentata</i> Blume Water Extract in Alleviating NAFLD: PPARγ-Driven Synergistic Regulation of Lipid Metabolism and Macrophage Efferocytosis.\",\"authors\":\"Xiong Ying Li, Ru Meng Yao, Xiao Ming Zou, Yun Xu, Sha Ying Qiu, Ping Ping He, Li Jun Wang, Shan Shan Lei\",\"doi\":\"10.2174/0118715303385546250912094219\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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 <i>Achyranthes bidentata</i> water extract (ABW) on NAFLD in mice induced by high-fat-fed.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. <i>In vitro</i>, ABW suppressed the expression of pro-inflammatory genes (<i>Il1b, Il6, Tnf, and Nos2</i>) and enhanced the expression of macrophage efferocytosis-related genes (<i>Pparγ, Gas6, Tyro3, and Axl</i>) 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.</p><p><strong>Discussion: </strong>This study demonstrates that ABW ameliorates NAFLD by activating the PPARγ/LXRα signaling pathway and promoting macrophage efferocytosis.</p><p><strong>Conclusion: </strong>These findings provide a novel mechanistic insight into the therapeutic effects of multi- component herbal medicines for NAFLD.</p>\",\"PeriodicalId\":94316,\"journal\":{\"name\":\"Endocrine, metabolic & immune disorders drug targets\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Endocrine, metabolic & immune disorders drug targets\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2174/0118715303385546250912094219\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine, metabolic & immune disorders drug targets","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118715303385546250912094219","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Mechanistic Insights into Achyranthes Bidentata Blume Water Extract in Alleviating NAFLD: PPARγ-Driven Synergistic Regulation of Lipid Metabolism and Macrophage Efferocytosis.
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.
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