Enayati Ayesheh, Ghojoghnejad Mobina, Roufogalis Basil D, Maollem Seyed Adel, Sahebkar Amirhossein
Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Discipline of Pharmacology, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
PPAR Res. 2022 Aug 31;2022:4714914. doi: 10.1155/2022/4714914. eCollection 2022.
Peroxisome proliferator-activated receptors (PPARs) are members of the ligand-dependent nuclear receptor family. PPARs have attracted wide attention as pharmacologic mediators to manage multiple diseases and their underlying signaling targets. They mediate a broad range of specific biological activities and multiple organ toxicity, including cellular differentiation, metabolic syndrome, cancer, atherosclerosis, neurodegeneration, cardiovascular diseases, and inflammation related to their up/downstream signaling pathways. Consequently, several types of selective PPAR ligands, such as fibrates and thiazolidinediones (TZDs), have been approved as their pharmacological agonists. Despite these advances, the use of PPAR agonists is known to cause adverse effects in various systems. Conversely, some naturally occurring PPAR agonists, including polyunsaturated fatty acids and natural endogenous PPAR agonists curcumin and resveratrol, have been introduced as safe agonists as a result of their clinical evidence or preclinical experiments. This review focuses on research on plant-derived active ingredients (natural phytochemicals) as potential safe and promising PPAR agonists. Moreover, it provides a comprehensive review and critique of the role of phytochemicals in PPARs-related diseases and provides an understanding of phytochemical-mediated PPAR-dependent and -independent cascades. The findings of this research will help to define the functions of phytochemicals as potent PPAR pharmacological agonists in underlying disease mechanisms and their related complications.
过氧化物酶体增殖物激活受体（PPARs）是配体依赖性核受体家族的成员。作为管理多种疾病及其潜在信号靶点的药理介质，PPARs已引起广泛关注。它们介导广泛的特定生物学活性和多器官毒性，包括细胞分化、代谢综合征、癌症、动脉粥样硬化、神经退行性变、心血管疾病以及与其上下游信号通路相关的炎症。因此，几种类型的选择性PPAR配体，如贝特类药物和噻唑烷二酮类（TZDs），已被批准作为其药理激动剂。尽管有这些进展，但已知使用PPAR激动剂会在各种系统中引起不良反应。相反，一些天然存在的PPAR激动剂，包括多不饱和脂肪酸以及天然内源性PPAR激动剂姜黄素和白藜芦醇，由于其临床证据或临床前实验结果，已被作为安全激动剂引入。本综述重点关注植物来源的活性成分（天然植物化学物质）作为潜在安全且有前景的PPAR激动剂的研究。此外，它对植物化学物质在PPAR相关疾病中的作用进行了全面综述和评论，并提供了对植物化学物质介导的PPAR依赖性和非依赖性级联反应的理解。这项研究的结果将有助于确定植物化学物质作为强效PPAR药理激动剂在潜在疾病机制及其相关并发症中的作用。
