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靶向雷帕霉素哺乳动物靶点:炎症性肠病的治疗前景

Targeting Mammalian Target of Rapamycin: Prospects for the Treatment of Inflammatory Bowel Diseases.

作者信息

Lashgari Naser-Aldin, Roudsari Nazanin Momeni, Momtaz Saeideh, Ghanaatian Negar, Kohansal Parichehr, Farzaei Mohammad Hosein, Afshari Khashayar, Sahebkar Amirhossein, Abdolghaffari Amir Hossein

机构信息

Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.

出版信息

Curr Med Chem. 2021;28(8):1605-1624. doi: 10.2174/0929867327666200504081503.

Abstract

Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview of plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.

摘要

炎症性肠病(IBD)是一组慢性进行性疾病的统称。多种细胞和生物分子途径与IBD的发病机制有关,但其病因尚不清楚。肠道上皮细胞中雷帕霉素靶蛋白(mTOR)途径的激活也被证明可诱导炎症。本综述聚焦于mTOR信号通路的抑制及其在治疗IBD中的潜在应用。我们还概述了通过调节mTOR途径对IBD治疗有益的植物源化合物。数据来自1995年至2019年5月期间发表的英文临床、体外和体内研究,这些研究从PubMed、谷歌学术、Scopus和Cochrane图书馆数据库收集。各项研究结果表明,抑制mTOR信号通路可下调IBD中涉及的炎症过程和细胞因子。在此背景下,一些天然产物可能会逆转该疾病的病理特征。此外,mTOR为IBD提供了一个新的药物靶点。需要全面的临床研究来证实mTOR抑制剂治疗IBD的疗效。

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