关键词: Gut microbiota Gypenoside aglycones Hyperlipidemia Lipid metabolism Therapeutic intervention

Mesh : Rats Animals Diet, High-Fat / adverse effects Gastrointestinal Microbiome Gynostemma Hyperlipidemias / drug therapy metabolism Triglycerides / metabolism Lipid Metabolism Cholesterol, LDL / metabolism Plant Extracts

来  源:   DOI:10.1016/j.jep.2024.118066

Abstract:
BACKGROUND: Gynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum, have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota.
OBJECTIVE: This study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia.
METHODS: A hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition.
RESULTS: Agl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus, Akkermansia, and Blautia and promoted specific shifts in Lactobacillus murinus, Firmicutes bacterium CAG:424, and Allobaculum stercoricanis.
CONCLUSIONS: This comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management.
摘要:
背景:绞股蓝(Thunb。)牧野在中医中具有治疗脂质异常的传统应用。绞股蓝皂甙(GP),绞股蓝的主要生物活性成分,据报道,通过多种机制发挥降血脂作用。GP的降脂作用可能归因于由肠道微生物群水解GP产生的糖苷配基部分。然而,到目前为止,没有关于绞股蓝皂甙苷配基(Agl)是否,主要的生物活性成分,可以通过调节肠道菌群来改善高脂血症。
目的:本研究探讨了绞股蓝皂甙苷苷元(Agl)在高脂饮食(HFD)诱导的高脂血症大鼠模型中的潜在治疗作用。
方法:用高脂饮食喂养大鼠建立高脂血症大鼠模型。Agl口服给药,和血脂水平进行分析。分子技术,包括RT-聚合酶链反应(PCR)和粪便微生物群测序,用于研究Agl对脂质代谢和肠道菌群组成的影响。
结果:Agl给药显著降低血清总胆固醇(TC)水平,甘油三酯(TG),和低密度脂蛋白胆固醇(LDL-C),减轻HFD引起的肝损害。分子研究揭示了Agl对关键脂质代谢基因和蛋白质的调节。值得注意的是,Agl治疗丰富了肠道微生物群的有益属,包括乳酸菌,Akkermansia,和布劳特氏菌,促进了鼠乳杆菌的特定变化,厚壁菌细菌CAG:424,和胸骨Allobaculum。
结论:这项综合研究将Agl确立为治疗高脂血症的有希望的候选药物。它还表现出显著的降血脂和保肝特性。脂质代谢相关基因的调节,随着肠道菌群平衡的恢复,提供机械见解。因此,Agl在高脂血症管理中具有巨大的临床应用潜力。
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