Impact of natural compounds on peroxisome proliferator-activated receptor: Molecular effects and its importance as a novel therapeutic target for neurological disorders

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.