Hypericum monogynum L. extract inhibits human aortic valve interstitial cell calcification by interfering with the EGFR/PI3K/AKT signaling pathway

Calcific aortic valve disease (CAVD) is a serious heart valve condition with an increasing global prevalence. Currently, the transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) is the only treatment strategy, and no available pharmaceutical treatments for CAVD. The purpose of our study was to seek drugs to inhibit human aortic valve interstitial cells (hVICs) osteogenic differentiation, which are believed to play a crucial role in CAVD development, and explore the mechanism of drug treatment for CAVD. In this study, we screened an in-house compound library (88 compounds) using dot-blotting and selected the natural compound chipericumin D as the candidate compound which was extracted from the Hypericum monogynum L., showing VICs osteogenic differentiation inhibitory activity. Network pharmacology analysis, molecular docking, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) indicated the binding of chipericumin D to the epidermal growth factor receptor (EGFR). Moreover, chipericumin D was shown to inhibit the EGFR, PI3K, and AKT signaling pathway in VICs under osteogenic medium (OM) conditions. Our research findings indicate that chipericumin D holds promise as a potential drug for the treatment of CAVD, and we have preliminary evidence suggesting that EGFR is a novel therapeutic target for CAVD.