Tanshinone IIA and sodium tanshinone IIA sulfonate in ischemic stroke: evidence, exposure, and translational readiness.

Abstract

Ischemic stroke remains a major cause of death and long-term disability despite reperfusion therapy. Tanshinone IIA (Tan IIA), a lipophilic diterpene quinone, and sodium tanshinone IIA sulfonate (STS), its water-soluble sulfonated derivative, show broad activity in experimental cerebral ischemia. They are often treated as interchangeable despite differences in formulation and exposure. We critically reviewed representative pharmacological, preclinical, formulation, and clinical evidence through 28 July 2026. We distinguished active entity, formulation, causal support, replication, exposure linkage, treatment window, and patient-centered relevance. Reported effects span oxidative and mitochondrial injury, endothelial barrier failure, neuroinflammation, regulated cell death, metabolism, and repair. Most pathway claims, however, rely on single laboratories, early dosing, young healthy rodents, short follow-up, or surrogate outcomes. Human evidence comprises one 42-patient STS-plus-rt-PA trial and a 2025 meta-analysis of 22 trials involving 2,289 participants. These findings suggest short-term signals but do not establish benefits for ordinal disability, survival, recurrent stroke, or uncommon bleeding. An injectable product and human plasma pharmacokinetic methods make STS more operationally tractable; superior efficacy remains unproven. Progression should require a fixed product, exposure-linked target engagement, durable benefit in aged and comorbid reperfusion models, and independent multicenter validation. Biological plausibility remains substantially stronger than translational readiness.