Ginsenosides retard atherogenesis via remodelling host–microbiome metabolic homeostasis

作者：Yun Wang, Jiawei Wu, Yu Hong, Jia‐Ying Zhu, Youcai Zhang, Jun Zhang, Chujie Ding, Yuan Che, Guangji Wang, Aiqin Jiang, Haiping Hao, Lijuan Cao · 发表于：British Journal of Pharmacology · 年份：2024 · DOI：10.1111/bph.16320 · 被引用次数：24 · 研究领域：Ginseng Biological Effects and Applications、Gut microbiota and health、Lipid metabolism and disorders

Abstract Background and Purpose Panax ginseng is widely applied in the adjuvant treatment of cardiometabolic diseases in clinical practice without clear mechanisms. This study aims to clearly define the efficacy and underlying mechanism of P. ginseng and its active components in protecting against atherosclerosis. Experimental Approach The anti‐atherogenic efficacy of total ginseng saponin extract (TGS) and its components was evaluated on Ldlr −/− mice. Gut microbial structure was analysed by 16S rRNA sequencing and PCR. Bile acid profiles were revealed using targeted metabolomics with LC–MS/MS analysis. The contribution of gut microbiota to atherosclerosis was assessed by co‐housing experiments. Key Results Ginsenoside Rb1, representing protopanaxadiol (PPD)‐type saponins, increased intestinal Lactobacillus abundance, resulting in enhanced bile salt hydrolase (BSH) activity to promote intestinal conjugated bile acid hydrolysis and excretion, followed by suppression of enterohepatic farnesoid X receptor (FXR)–fibroblast growth factor 15 (FGF15) signal, and thereby increased cholesterol 7α‐hydroxylase (CYP7A1) transcriptional expression and facilitated metabolic elimination of cholesterol. Synergistically, protopanaxatriol (PPT)‐type saponins, represented by ginsenoside Rg1, protected against atherogenesis‐triggered gut leak and metabolic endotoxaemia. Ginsenoside Rg1 directly induced mucin production to nutritionally maintain Akkermansia muciniphila , which reciprocally inhib...