Investigating the Fracture Treatment Mechanism of Dipsacus asper Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation
Abstract
This study investigated the active components of Dipsacus asper (DA)in promoting fracture healing and their molecular mechanisms. The DA chemical constituents were sourced from the TCMSP and HERB databases. Six key components were identified based on the top six Degree values, including Japonine, ursolic acid, and Sweroside aglycone, among which exhibited the binding energy with NTRK1 (-6.69 kcal/mol), MMP9 (-6.62 kcal/mol), and CA2 (-5.86 kcal/mol). KEGG enrichment analysis revealed that Dipsacus asper primarily modulates the MAPK signaling pathway (promoting cell proliferation), the AGE-RAGE pathway (regulating the bone microenvironment), and ECM remodeling pathways (such as pathways in cancer). Molecular dynamics simulations demonstrated that all complexes reached stable RMSD values within 2-3 ns (fluctuations < 0.1-1 nm). A decrease in Rg values indicated more compact structures, and the CA2-Sweroside aglycone complex maintained an average of one hydrogen bond, confirming stable binding.By modulating multiple pathways such as MAPK and AGE-RAGE, it facilitates osteogenic differentiation, suppresses inflammation, and accelerates bone matrix remodeling. After MS/MS verification, the presence of Japonine in the medicinal extract was ruled out. The integrative strategy of "component-target-pathway" established in this research introduces a fresh framework for explaining how Chinese medicine works.