Sodium Tanshinone IIA Sulfonate Ameliorates Fibrosis of Skeletal Muscle Injury by Regulating Transforming Growth Factor‐β1/Smad3 and Phosphoinositide 3‐Kinase/protein Kinase B/Cyclooxygenase‐2 Signaling Pathways

ABSTRACT Sodium tanshinone IIA sulfonate exerts several pharmacological effects; however, its mechanism in skeletal muscle injuries remains unknown. We explored the biological function of sodium tanshinone IIA sulfonate in skeletal muscle injury and elucidated its underlying mechanisms. We established a skeletal muscle injury model following blunt trauma and transforming growth factor‐β1‐induced NIH/3T3 cell models. Morphological changes, collagen deposition, and fibrosis in the muscle tissues were evaluated, and cell proliferation was determined. The expression of myogenic differentiation markers in C2C12 cells, including myogenic differentiation 1 and myosin heavy chain, and the activity of the transforming growth factor‐β1/Smad3 and phosphoinositide 3‐kinase/protein kinase B/cyclooxygenase‐2 signaling pathway were measured. Compared to the model group, the sodium tanshinone IIA sulfonate‐treated group showed reduced inflammatory cell infiltration, collagen deposition, and fibrosis. Transforming growth factor‐β1 and cyclooxygenase‐2 expression and Smad3 and phosphoinositide 3‐kinase/protein kinase B pathway activation were inhibited by sodium tanshinone IIA sulfonate. In vitro, sodium tanshinone IIA sulfonate treatment significantly reduced NIH/3T3 cell proliferation and downregulated p‐Smad3, transforming growth factor‐β1, and cyclooxygenase‐2 expression in a dose‐dependent manner. Moreover, sodium tanshinone IIA sulfonate enhanced myogenic differentiation 1 and myosin heavy chain expression in C2C12 cells. Furthermore, sodium tanshinone IIA sulfonate inhibited the activation of transforming growth factor‐β1/Smad3 and phosphoinositide 3‐kinase/protein kinase B/cyclooxygenase‐2 signaling pathway in skeletal muscle fibrosis. Thus, sodium tanshinone IIA sulfonate exerted a suppressive effect on skeletal muscle fibrosis via the transforming growth factor‐β1/Smad3 and phosphoinositide 3‐kinase/protein kinase B/cyclooxygenase‐2 signaling pathways, providing a new therapeutic approach for skeletal muscle fibrosis.