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黄酮类化合物介导的 SIRT1 信号通路激活与肝脏疾病

Flavonoids-mediated SIRT1 signaling activation in hepatic disorders.

机构信息

Biochemistry Laboratory, Chemistry Department, Faculty of Science, Assiut University, Egypt.

Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University-Assiut Branch, Egypt.

出版信息

Life Sci. 2020 Oct 15;259:118173. doi: 10.1016/j.lfs.2020.118173. Epub 2020 Aug 1.

Abstract

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (-)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases.

摘要

各种肝脏疾病在全球范围内的患病率显著增加,被视为严重的健康问题。沉默调节蛋白(Sirtuins)是细胞周期、线粒体生物发生、胰岛素分泌、氧化还原平衡、炎症和细胞凋亡等多种细胞过程的主要战略调控因子之一。SIRT1 是沉默调节蛋白中最突出和广泛研究的成员,与健康状况和长寿有关。因此,靶向 SIRT1 信号通路可能是治疗各种疾病(包括肝脏疾病)的合理治疗方法。类黄酮是广泛存在于不同植物中的多酚化合物,对多种疾病具有有益的作用。在本综述中,我们重点介绍了类黄酮、(-)-表儿茶素、ampelopsin、黄芩苷、飞燕草素、漆黄素、没食子儿茶素-3-没食子酸酯、木樨草素、松属素、槲皮素、水飞蓟素、反式查耳酮和黄腐醇,以验证它们潜在的有希望的保肝作用是否与 SIRT1 的激活有关。此外,还应用分子建模模拟来探索这些类黄酮与 SIRT1 的潜在结合模式。综合信息和分子对接模拟表明,SIRT1 信号参与了类黄酮在不同肝脏疾病中的有益药理作用。

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