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藏医三果汤预防非酒精性脂肪性肝病的作用机制。

Preventive mechanisms of Chinese Tibetan medicine Triphala against nonalcoholic fatty liver disease.

机构信息

Research Center for High Altitude Medicine, Key Laboratory of High-Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining, China.

College of Eco-Environmental Engineering, Qinghai University, Xining, China.

出版信息

Phytomedicine. 2024 Jan;123:155229. doi: 10.1016/j.phymed.2023.155229. Epub 2023 Nov 20.

Abstract

BACKGROUND

Triphala (TLP), as a Chinese Tibetan medicine composing of Emblica officinalis, Terminalia chebula and Terminalia bellirica (1.2:1.5:1), exhibited hepatoprotective, hypolipidemic and gut microbiota modulatory effects. Nonetheless, its roles in prevention of high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and the related mechanistic insights involving the interplay of gut microbiota and hepatic inflammation are not known.

PURPOSE

The present study seeks to determine if TLP would prevent HFD-induced NAFLD in vivo and its underlying mechanisms from the perspectives of gut microbiota, metabolites, and hepatic inflammation.

METHODS

TLP was subjected to extraction and chemo-profiling, and in vivo evaluation in HFD-fed rats on hepatic lipid and inflammation, intestinal microbiota, short-chain fatty acids (SCFAs) and permeability, and body weight and fat content profiles.

RESULTS

The TLP was primarily constituted of gallic acid, corilagin and chebulagic acid. Orally administered HFD-fed rats with TLP were characterized by the growth of Ligilactobacillus and Akkermansia, and SCFAs (acetic/propionic/butyric acid) secretion which led to increased claudin-1 and zonula occludens-1 expression that reduced the mucosal permeability to migration of lipopolysaccharides (LPS) into blood and liver. Coupling with hepatic cholesterol and triglyceride lowering actions, the TLP mitigated both inflammatory (ALT, AST, IL-1β, IL-6 and TNF-α) and pro-inflammatory (TLR4, MYD88 and NF-κB P65) activities of liver, and sequel to histopathological development of NAFLD in a dose-dependent fashion.

CONCLUSION

TLP is promisingly an effective therapy to prevent NAFLD through modulating gut microbiota, mucosal permeability and SCFAs secretion with liver fat and inflammatory responses.

摘要

背景

三果汤(TLP)是一种由余甘子、诃子和使君子(1.2:1.5:1)组成的藏药,具有保肝、降血脂和调节肠道微生物群的作用。然而,其在预防高脂肪饮食(HFD)诱导的非酒精性脂肪性肝病(NAFLD)中的作用及其涉及肠道微生物群和肝炎症相互作用的相关机制尚不清楚。

目的

本研究旨在从肠道微生物群、代谢物和肝炎症的角度,确定 TLP 是否可以预防体内 HFD 诱导的 NAFLD 及其潜在机制。

方法

对 TLP 进行提取和化学分析,并在 HFD 喂养的大鼠体内进行评估,观察其对肝脂质和炎症、肠道微生物群、短链脂肪酸(SCFAs)和通透性以及体重和脂肪含量的影响。

结果

TLP 主要由没食子酸、鞣花酸和诃子酸组成。口服给予 TLP 的 HFD 喂养大鼠表现出 Ligilactobacillus 和 Akkermansia 的生长,以及 SCFAs(乙酸/丙酸/丁酸)的分泌,这导致 Claudin-1 和 Zonula Occludens-1 的表达增加,从而降低了 LPS 向血液和肝脏迁移的黏膜通透性。与肝胆固醇和甘油三酯降低作用相结合,TLP 以剂量依赖的方式减轻了肝的炎症(ALT、AST、IL-1β、IL-6 和 TNF-α)和促炎(TLR4、MYD88 和 NF-κB P65)活性,并随后阻止了 NAFLD 的组织病理学发展。

结论

TLP 有望通过调节肠道微生物群、黏膜通透性和 SCFAs 分泌来预防 NAFLD,从而降低肝脂肪和炎症反应。

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