Shuxin oral liquid attenuates isoproterenol-induced myocardial fibrosis in rats: Association with downregulation of the TGF-β/Smad signaling pathway

ETHNOPHARMACOLOGICAL RELEVANCE: Shuxin oral liquid (SX) is a traditional Chinese medicine formulation widely used for coronary heart disease (CHD) characterized by "Qi deficiency and blood stasis". Because myocardial fibrosis (MF) contributes to adverse cardiac remodeling in ischemic heart disease, investigating the anti-fibrotic potential of SX may provide pharmacological evidence related to its traditional use. AIM OF THE STUDY: This study aimed to investigate the protective effects of SX on isoproterenol (ISO)-induced MF in rats and to examine whether these effects were accompanied by changes in transforming growth factor-β (TGF-β)/Smad pathway-related protein expression. MATERIALS AND METHODS: MF was induced by ISO (5.0 mg/kg, subcutaneous injection) for 7 consecutive days in each cohort. SX (2.16, 4.32, and 8.64 g/kg, intragastric administration) was administered once daily from Day 1 to Day 14, Day 28, or Day 42, with ISO injection scheduled on Days 1-7, Days 15-21, or Days 29-35, respectively. ECG abnormalities, histopathology, serum biochemical markers, and protein expression were evaluated. RESULTS: SX significantly alleviated ISO-induced myocardial injury, as evidenced by improved electrocardiographic abnormalities, increased body weight, and reduced heart weight index, lactate dehydrogenase, and creatine kinase-MB levels. SX also markedly reduced MF, as indicated by decreased fibrotic area and collagen I expression. In parallel, SX reduced myocardial TGF-β and phosphorylated Smad2/3 levels without markedly affecting total Smad2/3 expression, suggesting an association between SX treatment and downregulation of TGF-β/Smad pathway-related protein expression. CONCLUSION: SX effectively attenuated MF in ISO-induced rats, possibly in association with downregulation of the TGF-β/Smad pathway-related proteins.