Traditional Chinese medicine interventions targeting Wnt/β-catenin signaling in cerebral ischemia/reperfusion injury: a review.

Vascular recanalization therapy for ischemic stroke commonly induces cerebral ischemia-reperfusion injury (CIRI), which causes secondary neural damage and substantially limits clinical benefit. The canonical Wnt/β-catenin signaling pathway has a central role in regulating central nervous system cell survival, vascular homeostasis, inflammatory balance, and neuroregeneration, making it a highly promising neuroprotective target for CIRI. Traditional Chinese medicine (TCM), including herbal-derived active compounds, compound formulas, and acupuncture, has distinctive multitarget regulatory advantages that are well aligned with the complex pathological features of CIRI. Existing basic studies indicate that TCM interventions can activate this pathway by inhibiting GSK-3β activity, stabilizing β-catenin, and promoting its nuclear translocation, thereby exerting multiple effects, including anti-apoptotic activity, blood-brain barrier (BBB) protection, anti-inflammatory and antioxidant actions, and promotion of neurogenesis and angiogenesis. This review systematically elucidates the molecular mechanisms by which Wnt/β-catenin signaling participates in CIRI-induced injury and repair, comprehensively summarizes the experimental evidence and action patterns of TCM interventions targeting this pathway for neuroprotection, and discusses the current limitations and future prospects for translating basic research into clinical application. This review aims to provide a solid theoretical basis for precision integrated Chinese-Western interventions in ischemic stroke and for the development of new neuroprotective agents.