Neurological disorders refer to the pathological changes of the nervous system involving multiple pathological mechanisms characterized by complex pathogenesis and poor prognosis. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor that is a member of the nuclear receptor superfamily. PPAR has attracted considerable attention in the past decades as one of the potential targets for the treatment of neurological disorders. Several in vivo and in vitro studies have confirmed that PPARs play a neuroprotective role by regulating multiple pathological mechanisms. Several selective PPAR ligands, such as thiazolidinediones and fibrates, have been approved as pharmacological agonists. Nevertheless, PPAR agonists cause a variety of adverse effects. Some natural PPAR agonists, including wogonin, bergenin, jujuboside A, asperosaponin VI, monascin, and magnolol, have been introduced as safe agonists, as evidenced by clinical or preclinical experiments. This review summarizes the effects of phytochemicals on PPAR receptors in treating various neurological disorders. Further, it summarizes recent advances in phytochemicals as potential, safe, and promising PPAR agonists to provide insights into understanding the PPAR-dependent and independent cascades mediated by phytochemicals. The phytochemicals exhibited potential for treating neurological disorders by inhibiting neuroinflammation, exerting anti-oxidative stress and anti-apoptotic activities, promoting autophagy, preventing demyelination, and reducing brain edema and neurotoxicity. This review presents data that will help clarify the potential mechanisms by which phytochemicals act as pharmacological agonists of PPARs in the treatment of neurological disorders. It also provides insights into developing new drugs, highlighting phytochemicals as potential, safe, and promising PPAR agonists. Additionally, this review aims to enhance understanding of both PPAR-dependent and independent pathways mediated by phytochemicals.

中文翻译：

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天然化合物对过氧化物酶体增殖物激活受体的影响：分子效应及其作为神经系统疾病新治疗靶点的重要性


神经系统疾病是指神经系统的病理变化，涉及多种病理机制，其特征是发病机制复杂、预后不良。过氧化物酶体增殖物激活受体 （PPAR） 是一种配体激活的转录因子，是核受体超家族的成员。PPAR 作为治疗神经系统疾病的潜在靶点之一，在过去几十年中引起了相当大的关注。多项体内和体外研究证实，PPARs 通过调节多种病理机制发挥神经保护作用。几种选择性 PPAR 配体，例如噻唑烷二酮类和贝特类药物，已被批准用作药物激动剂。然而，PPAR 激动剂会引起多种不良反应。临床或临床前实验证明，一些天然 PPAR 激动剂，包括汉黄素、贝尔根素、红枣苷 A、天冬皂苷 VI、莫纳霉素和厚朴醇，已被作为安全的激动剂引入。本文总结了植物化学物质对 PPAR 受体治疗各种神经系统疾病的影响。此外，它总结了植物化学物质作为潜在、安全和有前途的 PPAR 激动剂的最新进展，为理解植物化学物质介导的 PPAR 依赖性和独立级联反应提供了见解。植物化学物质通过抑制神经炎症、发挥抗氧化应激和抗凋亡活性、促进自噬、防止脱髓鞘以及减少脑水肿和神经毒性，显示出治疗神经系统疾病的潜力。本综述提供的数据将有助于阐明植物化学物质在治疗神经系统疾病中作为 PPARs 的药理激动剂的潜在机制。 它还为开发新药提供了见解，强调植物化学物质是潜在、安全和有前途的 PPAR 激动剂。此外，本综述旨在加强对植物化学物质介导的 PPAR 依赖性和独立途径的理解。