Bridging ethnobotany and neuro-pharmacology: exploring South Africa’s indigenous plants for brain health

South Africa’s extensive floral biodiversity and ethnobotanical history represent a vast, underexplored resource for neurology, with over 300 species traditionally used for CNS ailments like epilepsy, anxiety, and cognitive decline. This paper advocates for a multi-targeted therapeutic strategy as an essential alternative to the insufficient “one drug, one target” conventional approach, given that complex neurological disorders are multifactorial, involving issues like neurotransmitter imbalance, neuroinflammation, and oxidative stress. Plant extracts, rich in bioactive compounds (alkaloids, flavonoids, phenols, and terpenoids), are uniquely suited for this approach, exemplified by Sceletium tortuosum alkaloids acting as serotonin reuptake inhibitors (SRIs) and Boophone disticha alkaloids showing acetylcholinesterase (AChE) inhibitory activity, with other species like Sutherlandia frutescens alleviating mitochondrial dysfunction. However, scientific translation is significantly impeded by a pervasive lack of human clinical trials (RCTs), considerable chemical variability in traditional remedies, and critical ethical and ecological challenges surrounding bioprospecting. To bridge this gap, future efforts must prioritize rigorous clinical validation, implement stringent Standardization and Quality Control (QC) using advanced analytical techniques, and strictly adhere to Access and Benefit-Sharing (ABS) principles to ensure sustainable and equitable commercial development.