Synergistic effects of tanshinone IIA and mesenchymal stem cells on neuroprotection, cardiovascular repair, tissue regeneration, muscle protein synthesis, and gut microbiota modulation across neurodegenerative, cardiovascular, and regenerative disease models.

Neurodegenerative, cardiovascular, and regenerative disorders remain major causes of disability and mortality worldwide, necessitating the development of multimodal therapeutic strategies. Tanshinone IIA (Tan IIA), a bioactive diterpenoid isolated from Salvia miltiorrhiza, possesses potent antioxidant, anti-inflammatory, anti-apoptotic, and pro-angiogenic properties. Mesenchymal stem cells (MSCs) have emerged as promising regenerative therapeutics owing to their differentiation potential, immunomodulatory capacity, and paracrine effects. Growing evidence indicates that the combination of Tan IIA and MSCs exerts synergistic therapeutic effects by enhancing MSC survival, proliferation, migration, and regenerative function while mitigating oxidative stress and inflammatory injury. This review summarizes current evidence regarding the combined effects of Tan IIA and MSCs on neuroprotection, cardiovascular repair, tissue regeneration, muscle protein synthesis, and gut microbiota modulation across neurodegenerative, cardiovascular, and regenerative disease models. The underlying molecular mechanisms involve the regulation of PI3K/Akt, Wnt/β-catenin, TGF-β/Smad, and Nrf2 signaling pathways, together with improvements in angiogenesis, immune homeostasis, mitochondrial function, and cellular metabolism. Emerging evidence also suggests that modulation of the gut microbiota may contribute to enhanced systemic immune regulation and regenerative outcomes, whereas improvements in muscle protein synthesis may support tissue recovery and functional restoration. Although preclinical findings are promising, further mechanistic investigations and well-designed clinical trials are required to optimize treatment protocols and establish the efficacy, safety, and translational potential of this combinational therapeutic strategy.