[Panax notoginseng saponins mediated inhibition of human aortic valve interstitial cell calcification via SYK/NF-κB pathway].

Using bioinformatics analysis, network pharmacology, and cellular experiments, this study investigated the effects and potential mechanisms of Panax notoginseng saponins(PNS) on osteogenic induction of immortalized human aortic valve interstitial cells(hVICs). A calcific aortic valve disease(CAVD) cell model was established by treating hVICs with osteogenic induction medium(OM). Experimental groups included a control group, a model group, and PNS treatment groups(0.075, 0.05, and 0.025 mg·mL~(-1)). Cell viability was assessed by the CCK-8 assay. Calcification was evaluated by alkaline phosphatase(ALP) and alizarin red S staining. Western blot was performed to measure the expression of calcification-related proteins runt-related transcription factor 2(RUNX2), bone morphogenetic protein 2(BMP2), and ALP. Transcriptomic datasets related to CAVD were obtained from the Gene Expression Omnibus(GEO) database, and CAVD disease targets were retrieved from GeneCards. Active components of PNS and their potential targets were collected from HERB, Batman-TCM 2.0, and ETCM databases. The intersecting genes were subjected to protein-protein interaction(PPI) network construction, Gene Ontology(GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses, identifying the spleen tyrosine kinase(SYK)/nuclear factor kappa-B(NF-κB) signaling pathway as a core pathway. Western blot was then used to assess the effects of PNS at the optimal concentration on SYK/NF-κB pathway-related proteins. NF-κB p65 nuclear translocation was examined by immunofluorescence co-localization, and ELISA was applied to measure tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) levels. RESULTS:: showed that PNS reduced alizarin red S and ALP staining in calcification-induced hVICs and downregulated calcification-related proteins BMP2, ALP, and RUNX2(P