Modulation of transforming growth factor-beta signaling pathway mediates the effects of Kangxian Formula on cardiac remodeling

Ethnopharmacological relevance Kangxian formula (KXF) is a traditional Chinese medicine which shows effective outcomes in treating cardiac remodeling induced by hypertension. However, the exact effects and the mechanisms involved remain obscure. Aim of the study In this study, we aimed to identify the therapeutic role of KXF in vivo and in vitro, and investigate the mechanism of KXF on hypertension induced cardiac remodeling. Materials and methods After quality control of KXF using fingerprint, blood pressure, cardiac structure/function indexes, and degree of myocardial collagen were measured in vivo. Moreover, the proliferation, migration, and fibroblast-to-myofibroblast transformation (FMT) of cardiac fibroblasts (CFBs) were determined. Using gene chip, the related mechanisms of KXF treatment on cardiac remodeling were identified and further validated by western blot and polymerase chain reaction. Results A stable quality control standard of KXF was established in this study. KXF administration ameliorated systolic/diastolic blood pressure, cardiac damages, and cardiac fibrosis in vivo. The proliferation, migration, and FMT of CFBs were also inhibited by the treatment of KXF medicated serum. Furthermore, KXF reduced the protein level of transforming growth factor-beta (TGF-β) receptors Ⅰ, Ⅱ, Tak1, p38, Smad2/3, and Smad4 and the expression of mRNA, which are the hub proteins in the TGF-β signaling pathway. Conclusion Our findings suggest that KXF attenuates cardiac remodeling by improving cardiac damages, attenuating cardiac fibrosis, and inhibiting the activity of CFBs. In addition, KXF ameliorates cardiac remodeling partially through modulating the TGF-β signaling pathway. These data provide insights and mechanisms into the wide application of KXF in clinical practice.