Search for a command to run...
Introduction: This review aims to synthesize the latest research on natural medicines, particularly flavonoids, saponins, alkaloids, terpenoids, phenolic acids, glycosides, and polyphenols for treating ischemic and hemorrhagic stroke. Methods: A comprehensive literature search was conducted across PubMed, Web of Science, and CNKI for preclinical and clinical studies published between 2010 and 2025. Inclusion criteria were (i) original peer-reviewed articles, (ii) experimental or clinical evaluation of purified natural compounds or standardized extracts, and (iii) reported outcomes related to stroke pathophysiology. Data were qualitatively synthesized and, where feasible, quantitatively summarized by compound class. Results: Across classes, compounds reduced mean infarct volume by 30-55% and improved neurological score by 1.8-2.4 points versus vehicle. Common mechanisms: suppression of NF- κB/MAPK, activation of Nrf2/PI3K/Akt, and M2 microglial polarization. Nano-formulations increased brain exposure 5- to 20-fold, conferring an additional 15–25% protection. To date, only tetramethylpyrazine, Ginkgo biloba extract EGb 761, and ginsenoside Rd have progressed to human trials; most other compounds lack pharmacokinetic or toxicity profiles. Discussion: Reproducible efficacy exists, but translation is hindered by low oral bioavailability, species heterogeneity, and limited data in aged animals or models with comorbidities. Nanocarriers and rationally designed combination therapies represent promising strategies to overcome these limitations and should be integrated early in development. Conclusion: Natural medicines offer pleiotropic, mechanistically coherent neuroprotection in experimental stroke. Rigorous, adequately powered clinical trials, preferably employing optimized delivery strategies to overcome blood–brain-barrier constraints, are urgently needed to validate efficacy and establish evidence-based adjunctive therapies alongside the current standard of clinical care.