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Background: Herbal interventions have been integral to traditional medical systems worldwide, including Ayurveda, Traditional Chinese Medicine, and African ethnomedicine. With the rising prevalence of central nervous system (CNS) disorders, there is increasing scientific interest in validating these traditional remedies and exploring their neuroprotective potential. Objectives: To provide a global, up-to-date synthesis of ethnopharmacological evidence and experimental data on herbal interventions with reported CNS activity, and to highlight promising plant species and mechanistic pathways for future drug discovery Methods: We performed a systematic search of PubMed/MEDLINE, Embase, Web of Science, Scopus, Cochrane Library and selected regional databases from inception through 2025 for primary ethnobotanical surveys, preclinical studies, and clinical trials reporting CNS effects of medicinal plants. Inclusion criteria encompassed studies assessing plants for major CNS disorders (Alzheimer’s disease, Parkinson’s disease, epilepsy, depression, anxiety, schizophrenia, multiple sclerosis, stroke) or general neuroprotective/neuropharmacological activity. Data were extracted on species, traditional use, experimental model, outcomes, active constituents, and safety. Study quality was assessed using adapted risk-of-bias tools and findings were synthesized narratively and in disorder-specific tables. Results: Ethnobotanical and experimental evidence supports multiple plant species with CNS activity across world regions. Several species (e.g., Bacopa monnieri, Withania somnifera, Curcuma longa, Centella asiatica, Morinda citrifolia) have convergent preclinical and clinical evidence for cognitive, anxiolytic, antidepressant, or neuroprotective effects. Mechanisms include antioxidant, anti-inflammatory, cholinergic modulation, monoaminergic effects, and synaptic plasticity enhancement. However, heterogeneity in study quality, dosing, and phytochemical characterization limits firm conclusions. Conclusion: A growing global literature supports the potential of numerous medicinal plants as sources of CNS therapeutics. Future work should prioritize standardized phytochemical characterization, well-designed clinical trials, and integration of ethnobotanical knowledge with modern pharmacology to accelerate reverse-pharmacology pipelines.
Mishra et al. (Fri,) studied this question.