基于TGF-β1/Smad信号通路探讨桑枝总生物碱对糖尿病心肌纤维化的影响OA

Objective:To investigate the effect of Mulberry twig(Sangzhi)alkaloids(SZ-A),which is a new traditional Chinese medicinal,on myocardial fibrosis in diabetes mellitus(DM)and its underlying molecular mechanism.Methods:The diabetic mouse model was established using high-fat diet combined with streptozotocin injections.Mice were randomly divided into non-diabetic(ND),diabetic(DM),and SZ-A low-(50 mg/kg/d)or high-dose(100 mg/kg/d)groups.Myocardial fibrosis-related proteins(Collagen I,TGF-β1,Smad2/3,and their phosphorylated forms)were analyzed by Western blot,while mRNA levels of fibrosis markers(Collagen I/Ⅲ,α-SMA,Fn1,Postn)were quantified via qRT-PCR.Molecular docking simulations(AlphaFold2/Autodock)were performed to validate interactions between SZ-A components(DNJ,FGM,DAB)and TGF-β1.Results:SZ-A treatment significantly reduced myocardial Collagen deposition in diabetic mice,downregulated mRNA expression of Collagen I/Ⅲ,α-SMA,Fn1,and Postn(P<0.05),and suppressed TGF-β1 expression and Smad2/3 phosphorylation.Molecular docking revealed stable binding affinities between DNJ/FGM/DAB and TGF-β1.Exogenous TGF-β1 administration reversed SZ-A's anti-fibrotic effects,restoring Collagen I,TGF-β1,and p-Smad2/3 levels(P<0.05).Conclusion:SZ-A ameliorates diabetic myocardial fibrosis by targeting the TGF-β1/Smad signaling pathway,highlighting its therapeutic potential for diabetic cardiomyopathy.