
Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 6, 2025
Vascular calcification (VC) commonly occurs in diabetes and is associated with cardiovascular disease incidence mortality. Currently, there no drug treatment for VC. The Danlian-Tongmai formula (DLTM) a traditional Chinese medicine (TCM) prescription used diabetic VC (DVC), but its mechanisms of action remain unclear. This study aims to elucidate the effects DLTM on DVC explore underlying action. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was identify metabolites DLTM. A rat model established using streptozotocin (STZ) combined vitamin D3 (VitD3). were evaluated through alizarin red staining, calcium deposition, changes osteogenic contractile markers. specific molecular mechanism treating comprehensively analyzed by transcriptomics, docking vivo experimental verification. We identified 108 major In vivo, high-dose significantly alleviated rats. Transcriptomic analysis showed that markedly altered transcriptomic profile aortas, which regulating CCN3/NOTCH signaling pathway, promoting vascular smooth muscle contraction, inhibiting inflammatory responses. Molecular dynamics simulation demonstrated strong binding interactions between key molecules within including NOTCH1, DLL1, DLL4, hes1, hey1. experiments confirmed could upregulate CCN3, inhibit activation NOTCH ligands DLL1 downstream transcription factors hes1 hey1, reduce release cytokines IL6, IL1β, TNFα. alleviates axis Our research provides basis clinical transformation
Language: Английский