Catechins in stroke: multi-target mechanisms, preclinical evidence, and translational challenges

Abstract

Stroke is a leading cause of death and disability, with limited therapeutic options available. Catechin is a natural polyphenolic compound that exhibits significant neuroprotective effects. This review aims to summarize the pharmacokinetics of catechins, their neuroprotective mechanisms, preclinical evidence, and the translational challenges associated with both ischemic and hemorrhagic stroke. A structured literature search was conducted from 1985 to 2026 in PubMed, Web of Science, and Scopus, utilizing keyword combinations related to catechins and stroke. Current preclinical research findings indicate that catechins can alleviate oxidative inflammation, modulate microglial polarization, inhibit apoptosis, and restore autophagic function. Additionally, they can maintain blood-brain barrier integrity and mitochondrial function, as well as promote angiogenesis and neurogenesis. These protective effects have been validated in experimental models of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. However, the existing mechanistic evidence regarding their neuroprotective effects is predominantly derived from studies on (−)-epigallocatechin-3-gallate (EGCG), while research on other catechin monomers, green tea extracts, or mixed polyphenol preparations remains relatively scarce. Catechins represent promising candidate drugs for stroke due to their multiple neuroprotective potentials. However, most preclinical evidence arises from pretreatment paradigms, which are confounded by heterogeneity in dosage, age, and experimental models. Additionally, the low bioavailability and narrow therapeutic window of catechins restrict their clinical translation. Future research should prioritize the development of nano-delivery systems, the optimization of dosing regimens, and the validation of findings in aged and comorbid models.