甘草次酸通过Thbs1/PI3K-Akt/p53通路调节肠道菌群及其代谢物，改善胃粘膜损伤

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-09 DOI:10.1016/j.phymed.2025.156745

Zheng-Meng Jiang , Zhi-Yue Fang , Xing Yang , Xing-Xing Ji , Yuan-Yuan Zhao , Bin-Yan Lin , Ze-Bin Weng , E-Hu Liu

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引用次数: 0

摘要

背景：肠道菌群的失调是胃黏膜损伤（GMI）发生的关键。甘草次酸（Glycyrrhetinic acid， GA）是一种富含甘草根的生物活性三萜化合物。虽然GA在减轻GMI方面的潜力已得到认可，但其确切机制仍不清楚，特别是关于肠道微生物群的作用。目的探讨GA对HCl/乙醇诱导的大鼠GMI的保护作用及其机制。结果经H&；E染色显示，GA对大鼠胃粘膜具有明显的保护作用。利用粪便菌群移植，发现GA通过肠道菌群依赖机制显著减轻GMI大鼠的氧化损伤、炎症和凋亡相关基因的表达。16S rRNA测序和代谢组学分析显示，GA改善了HCl/乙醇引发的肠道生态失调和鞘脂、精氨酸和色氨酸代谢失衡。通过促进长双歧杆菌亚种的流行。婴儿（B.婴儿）在肠道微生物群中，GA改善与损伤相关的代谢紊乱。此外，其作用机制与抑制Thbs1/PI3K-Akt/p53信号通路有关。结论GA通过减轻肠道生态失调和促进婴儿B.婴定植来改善GMI。GA通过调节Thbs1/PI3K-Akt/p53通路，从而减轻与肠道微生物群失衡相关的炎症反应，具有治疗GMI的潜力。

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Glycyrrhetinic acid ameliorates gastric mucosal injury by modulating gut microbiota and its metabolites via Thbs1/PI3K-Akt/p53 pathway

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Glycyrrhetinic acid ameliorates gastric mucosal injury by modulating gut microbiota and its metabolites via Thbs1/PI3K-Akt/p53 pathway

Background

Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota.

Purpose

This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats.

Results

This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of Bifidobacterium longum subsp. infantis (B. infantis) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway.

Conclusion

The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of B. infantis. GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.