Yixiao Formula Suppresses Myocardial Fibrosis Through UpregulatingmiR-133a and Downregulating TGF-β/Smads Signal Molecules.

BACKGROUND: Yixiao formula (YXF), a traditional Chinese herbal medicine, has demonstrated clinical efficacy in alleviating symptoms of diabetic cardiomyopathy (DCM). The therapeutic mechanism underlying YXF's effects on DCM remains poorly understood. Myocardial fibrosis is a key pathogenic mechanism in DCM, and previous studies have indicated that miR-133a may be involved in its progression. Given that the TGF-β/Smads signaling pathway is a well-established mediator of myocardial fibrosis, investigating the mechanistic role of YXF through miR-133a and the TGF-β/Smads pathway warrants further exploration. OBJECTIVE: The main objective of this study is to investigate the potential contribution of the TGF-β/Smads pathway to the effects of YXF, as well as the role of miR133a, through in vivo DCM models and in vitro experiments. MATERIALS AND METHODS: Spontaneously diabetic KKAy mice were used to establish a DCM model by continuous high-fat feeding, with C57BL/6 mice as controls. Echocardiography, body weight, and blood glucose data were collected every 4 weeks to examine the effects of YXF on blood glucose levels and changes in cardiac function and structure in DCM mice. Immunohistochemistry, RT-qPCR, and western blot were used to detect the expression levels of the TGF-β/Smads pathway. Additionally, the potential molecular mechanism of YXF in mouse cardiac fibroblasts (MCFs) was investigated by knocking down miR-133a. RESULTS: YXF improved fasting blood glucose levels in DCM mice, promoted cardiac diastolic function, upregulated miR133a, and inhibited the expression of the TGF-β/Smads pathway. Furthermore, when miR133a inhibitors were transfected under YXF intervention, we found that YXF's inhibitory effect on the TGF-β/Smads pathway was weakened. CONCLUSION: Through this study, we found that YXF can increase miR133a and inhibit the expression of the TGF-β/Smads pathway, thereby inhibiting myocardial fibrosis and exerting a protective effect on DCM.