Paeonol as a Multi-Target Therapy for Neurological Disorders: Mechanistic Insights Into Neuroprotection.

BACKGROUND: Neurological disorders are a major global health challenge in the current era, and they need new therapeutic treatments. AIMS: This review evaluates the neurobiological activity of Paeonol (PNL) focusing on its antioxidant, anti-inflammatory, and cognitive enhancing effects in various neurodegenerative disorders. METHODS: A literature search (up to March 2025) was conducted via PubMed, ScienceDirect, Scopus, and other databases using MeSH terms related to PNL's pharmacology and neuroprotection. Inclusion criteria encompassed preclinical studies (in vitro and in vivo) and clinical trials, while exclusion criteria eliminated non-English papers and non-neurodegenerative research. RESULTS: PNL, a bioactive phenolic compound from Paeonia suffruticosa, has shown antioxidative, anti-inflammatory, and neuroprotective effects. PNL reduces oxidative stress by boosting the activity of superoxide dismutase (SOD) and glutathione (GSH) while decreasing reactive oxygen species (ROS) and lipid peroxidation. It also reduces neuroinflammation by inhibiting key pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), toll-like receptor 4 (TLR4), and mitogen-activated protein kinase (MAPK), and it affects apoptosis-related proteins like B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). In Alzheimer's disease (AD) models, PNL reduces amyloid-β plaques and some pro-inflammatory cytokines like interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), improving cognitive function. For ischemic stroke, it reduces infarction volume and microglial activation by targeting TLR2/4 and NF-κB. PNL has anticonvulsant effects in epilepsy and protects dopaminergic neurons in Parkinson's disease (PD). It also demonstrates anxiolytic and antidepressant properties by modulating Brain-Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), and oxidative stress markers. PNL is quickly absorbed with moderate bioavailability and low blood-brain barrier permeability. It effectively treats unstable angina but is less effective for osteoarthritis pain. Though safe at therapeutic doses, high concentrations can be cytotoxic. CONCLUSION: Further clinical research is needed to confirm its neurotherapeutic potential.