Rigano Daniela, Sirignano Carmina, Taglialatela-Scafati Orazio
Department of Pharmacy, University of Naples Federico II, Naples I-80131, Italy.
Acta Pharm Sin B. 2017 Jul;7(4):427-438. doi: 10.1016/j.apsb.2017.05.005. Epub 2017 Jun 16.
Peroxisome proliferator activated receptors (PPARs) , - and -/ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, rosiglitazone and pioglitazone) are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPAR, while PPAR is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPAR system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this "hot" target.
过氧化物酶体增殖物激活受体(PPARs)α、γ和α/γ是配体激活的转录因子,属于核激素受体超家族成员。这些受体通过调节基因表达在维持葡萄糖和脂质稳态中发挥关键作用。PPARs是一个公认的可成药靶点,事实上,用于治疗代谢疾病症状的几类药物,如血脂异常(贝特类药物,非诺贝特和吉非贝齐)和糖尿病(噻唑烷二酮类药物,罗格列酮和吡格列酮),都是各种PPAR亚型的配体。更确切地说,抗糖尿病噻唑烷二酮类药物作用于PPARγ,而PPARα是抗血脂异常贝特类药物的主要分子靶点。在过去几年中,我们对PPAR调节基因表达的机制的理解有了很大提高。本综述对调节PPAR系统的陆地和海洋天然产物进行了概述,目的是突出天然产物令人难以置信的化学多样性如何能为这个“热门”靶点提供创新线索。