Lupeol in neurodegenerative and neuropsychiatric disorders: Mechanisms and translational perspectives

Lupeol is a naturally occurring lupane-type pentacyclic triterpenoid widely distributed in dietary and medicinal plants and has attracted increasing interest as a potential neuroprotective compound. However, despite growing experimental evidence, its mechanistic and translational relevance has not been comprehensively evaluated. This review critically examines current evidence regarding the molecular, cellular and neurobehavioural effects of lupeol in neurodegenerative and neuropsychiatric disorders. Available preclinical studies indicate that lupeol modulates several interconnected pathological processes implicated in neurological disorders, including oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis, excitotoxicity and synaptic impairment. These effects include preservation of neuronal integrity, improved cognitive and behavioural outcomes, and enhanced neurotrophic and synaptic plasticity across multiple experimental models of Alzheimer's disease, Parkinson's disease, cerebral ischemia, traumatic brain injury and neuroinflammation. Current findings suggest that lupeol exerts multi-target neuroprotective effects through coordinated regulation of oxidative, inflammatory and neuronal signalling networks rather than through a single molecular mechanism. Despite these encouraging findings, clinical translation remains limited by poor aqueous solubility, low bioavailability and insufficient pharmacokinetic and human safety data. Overall, lupeol represents a promising candidate for further investigation in neurological disorders, although rigorous translational studies remain necessary to clarify its therapeutic applicability.