Phytochemical and Anti-Ischemic Stroke Properties from the Vitex L. Genus

Introduction: The genus Vitex L. (Verbenaceae) comprises ~250 species globally, with long-standing ethnopharmacological value. Notably, only Traditional Chinese Medicine (TCM) explicitly applies Vitex negundo for ischemic stroke (documented in classic Materia medica), distinguishing it from other regional uses (eg, menstrual disorders, malaria) and providing a unique basis for anti-stroke research. Materials and Methods: Through systematic searches of English and Chinese databases such as Web of Science, Pubmed, CNKI, and Wanfang Data. This review systematically summarizes the natural constituents of Vitex L. their anti-ischemic stroke efficacy, and underlying mechanisms, emphasizing the uniqueness of Vitex -specific components and guiding preclinical optimization and clinical translation. Results: Over 200 constituents were identified, with flavonoids (vitexin, isovitexin, casticin), terpenoids (vitexilactone, rotundifuran), and phenols as core active components. High-evidence compounds (validated by both in vitro and in vivo experiments) such as vitexin (10– 50 mg/kg) reduced rat MCAO infarct volume by 30– 40% via blocking NMDA receptor-mediated Ca 2 ⁺ overload. Mechanistically, components target neurons, glia, and vascular endothelial cells, regulating both classic pathways (Nrf2, NF-κB, PI3K/Akt) and frontier mechanisms (ferroptosis, pyroptosis, epigenetic regulation). Synergistic effects of multi-component mixtures and optimized extraction/synthesis address low-content challenges. Conclusion: Vitex L. exhibits significant anti-ischemic stroke potential, with unique components and multi-pathway regulation as core advantages. Future research should focus on multi-center validation, synergistic mechanism exploration, and clinical trials of high-evidence components to advance translation. Keywords: Vitex L., ischemic stroke, natural chemical constituents, neuroprotection, blood-brain barrier, flavonoid