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.
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.
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).
SZ-A ameliorates diabetic myocardial fibrosis by targeting the TGF-β1/Smad signaling pathway, highlighting its therapeutic potential for diabetic cardiomyopathy.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |