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绞股蓝总苷元对高脂饮食大鼠的降血脂作用及肠道菌群调节作用

Hypolipidemic effect and gut microbiota regulation of Gypenoside aglycones in rats fed a high-fat diet.

作者信息

Xie Jian, Luo Mingxia, Chen Qiuyi, Zhang Qianru, Qin Lin, Wang Yuhe, Zhao Yongxia, He Yuqi

机构信息

Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi, 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China; 2011 Cooperative Inovational Center for Guizhou Traditional Chinese Medicine and Ethnic Medicine Zunyi Medical University, Zunyi, 563000, China; Department of Medical Genetics, Zunyi Medical University, Zunyi, 563000, China.

Guizhou Engineering Research Center of Industrial Key-Technology for Dendrobium Nobile, Zunyi Medical University, Zunyi, 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China; 2011 Cooperative Inovational Center for Guizhou Traditional Chinese Medicine and Ethnic Medicine Zunyi Medical University, Zunyi, 563000, China.

出版信息

J Ethnopharmacol. 2024 Jun 28;328:118066. doi: 10.1016/j.jep.2024.118066. Epub 2024 Mar 16.

DOI:10.1016/j.jep.2024.118066
PMID:38499259
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

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.

AIM OF THE STUDY

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.

CONCLUSION

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

民族药理学相关性

绞股蓝在中国传统医学中用于治疗脂质异常。绞股蓝皂苷(GPs)是绞股蓝的主要生物活性成分,据报道可通过多种机制发挥降血脂作用。GPs的降脂作用可能归因于肠道微生物群对GPs水解产生的苷元部分。然而,迄今为止,关于主要生物活性成分绞股蓝皂苷苷元(Agl)是否能通过调节肠道微生物群改善高脂血症尚无报道。

研究目的

本研究探讨绞股蓝皂苷苷元(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

通过给大鼠喂食高脂饮食建立高脂血症大鼠模型。口服给予Agl,并分析血清脂质水平。采用包括逆转录聚合酶链反应(RT-PCR)和粪便微生物群测序在内的分子技术,研究Agl对脂质代谢和肠道微生物群组成的影响。

结果

给予Agl可显著降低血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平,并减轻HFD诱导的肝损伤。分子研究表明Agl可调节关键脂质代谢基因和蛋白质。值得注意的是,Agl治疗使肠道微生物群中有益菌属增加,包括乳酸杆菌属、阿克曼氏菌属和布劳特氏菌属,并促进了鼠乳杆菌、厚壁菌门细菌CAG:424和粪便别氏菌的特定变化。

结论

这项综合研究确定Agl是治疗高脂血症的有前景的候选药物。它还具有显著的降血脂和肝脏保护特性。脂质代谢相关基因的调节以及肠道微生物群平衡的恢复提供了作用机制。因此,Agl在高脂血症管理的临床应用中具有巨大潜力。

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