Traditional Chinese Medicine Targeting the Ischemic Cascade in Ischemic Stroke: Multitarget Mechanisms and Therapeutic Potential

ABSTRACT

Ischemic stroke (IS) remains a major cause of mortality and long‐term disability worldwide. Increasing evidence indicates that injury progression after cerebral ischemia is closely associated with dysfunction of the neurovascular unit (NVU). Following ischemia, a series of interconnected pathological events, including metabolic failure, excitotoxicity, calcium dysregulation, oxidative injury, inflammation and cell death, contribute to progressive neuronal and vascular damage. Traditional Chinese medicine (TCM) has been increasingly investigated as a source of multicomponent interventions for IS. Experimental studies indicate that bioactive compounds, extracts and classical formulas may influence multiple components of the ischemic cascade, including energy metabolism, glutamate excitotoxicity, Ca ²⁺ homeostasis, oxidative stress, neuroinflammation and regulated cell death. These effects have been associated with pathways including AMPK/SIRT1, PI3K/Akt, Nrf2/HO‐1, NF‐κB and NLRP3. However, modulation of multiple pathways does not necessarily establish pharmacological synergy or superiority over single‐target interventions. This review summarizes TCM interventions targeting the ischemic cascade, with a primary focus on studies published between 2015 and 2025. Particular attention is given to the strength of mechanistic evidence, treatment timing, experimental models, pharmacologically active constituents, safety and clinical translation. By critically evaluating both mechanistic findings and current limitations, this review provides a framework for assessing the evidence and translational potential of TCM‐derived neuroprotective strategies in IS.