Luo Han-Yan, Fang Jing, Zhang Wei-Hao, Chan Kam-Chun, Chan Yui-Man, Dong Cai-Xia, Li Song-Lin, Lyu Ai-Ping, Xu Jun
Institute of Systems Medicine and Health Science, School of Chinese Medicine, Hong Kong Baptist University, 999077, Hong Kong; Research Centre for Standardization of Chinese Medicines, School of Chinese Medicine, Hong Kong Baptist University, 999077, Hong Kong.
Research Centre for Standardization of Chinese Medicines, School of Chinese Medicine, Hong Kong Baptist University, 999077, Hong Kong.
J Adv Res. 2024 Dec 11. doi: 10.1016/j.jare.2024.12.002.
Ginseng demonstrates therapeutic potential in treating obesity, with both experimental and clinical studies suggesting its anti-obesity effects are mediated by gut microbiota. Nonetheless, the specific chemical components responsible for this effect remain largely unidentified.
This study aims to investigate the anti-obesity effects and mechanisms of ginseng polysaccharides (GP) and ginsenosides (GS), the primary chemical components of ginseng, with a focus on their impact on gut microbiota.
The impact of GP and GS on high-fat diet (HFD)-induced obesity was assessed using a mouse model. Molecular mechanisms were explored through a combination of chemical analysis, metagenomics, RT-qPCR, ELISA, and biochemical assays.
GP or GS administration effectively prevented adiposity in HFD-fed mice, and both effects were mediated by gut microbiota. Chemical analysis revealed diverse glycosyl groups in GP and GS. Metagenomics data suggested that GP-enriched species, e.g., Bacteroides stercorirosoris and Clostridiales bacterium encoded carbohydrate-active enzymes GH35, GH43 and PL9_1, while GS-enriched Sulfurospirillum halorespirans encoded GH16_5. These enzymes facilitated the utilization of glycosyl groups in GP and GS, selectively stimulating bacterial growth and reshaping the gut microbiota. Furthermore, bacterial species enriched by GP or GS encoded specific functional genes involved in short-chain fatty acid (SCFA) synthesis (K00625 and K00925 for GP; K18118, K00100, and K18122 for GS) and intestinal gluconeogenesis (IGN) (K01678, K00024, and K01596 for GP; K18118 and K00278 for GS). Consequently, the SCFA-GLP-1/PYY signaling and IGN were activated by both GP and GS to ameliorate obesity phenotypes.
GP and GS, containing diverse glycosyl groups, selectively stimulate specific gut bacteria, triggering mechanisms involved in SCFA-GLP-1/PYY signaling and IGN activation to reduce adiposity in HFD-fed mice. The study enhances understanding of the chemical components crucial for the gut microbiota-mediated anti-obesity effect of ginseng. The mechanistic understanding provides valuable insights for developing ginseng-based drugs or health products to combat obesity.
人参在治疗肥胖方面显示出治疗潜力，实验和临床研究均表明其抗肥胖作用是由肠道微生物群介导的。然而，造成这种作用的具体化学成分在很大程度上仍未明确。
本研究旨在探究人参的主要化学成分人参多糖（GP）和人参皂苷（GS）的抗肥胖作用及其机制，重点关注它们对肠道微生物群的影响。
使用小鼠模型评估GP和GS对高脂饮食（HFD）诱导的肥胖的影响。通过化学分析、宏基因组学、RT-qPCR、ELISA和生化测定相结合的方法探索分子机制。
给予GP或GS可有效预防HFD喂养小鼠的肥胖，且这两种作用均由肠道微生物群介导。化学分析揭示了GP和GS中存在多种糖基。宏基因组学数据表明，富含GP的物种，如粪便拟杆菌和梭菌目细菌编码碳水化合物活性酶GH35、GH43和PL9_1，而富含GS的嗜盐硫螺旋菌编码GH16_5。这些酶促进了GP和GS中糖基的利用，选择性地刺激细菌生长并重塑肠道微生物群。此外，由GP或GS富集的细菌物种编码参与短链脂肪酸（SCFA）合成的特定功能基因（GP的K00625和K00925；GS的K18118、K00100和K18122）和肠道糖异生（IGN）（GP的K01678、K00024和K01596；GS的K18118和K00278）。因此，GP和GS均激活了SCFA-GLP-1/PYY信号通路和IGN，以改善肥胖表型。
含有多种糖基的GP和GS选择性地刺激特定肠道细菌，触发SCFA-GLP-1/PYY信号通路和IGN激活所涉及的机制，以减少HFD喂养小鼠的肥胖。该研究加深了对人参肠道微生物群介导的抗肥胖作用至关重要的化学成分的理解。这种机制性理解为开发抗肥胖的人参基药物或保健品提供了有价值的见解。
