Targeting pathological osteogenic differentiation has emerged as one of the most promising therapeutic avenues in calcific aortic valve disease (CAVD), however, current treatments are limited to high-risk surgical replacements, and no approved pharmaceutical therapies exist to halt or reverse the disease progression. If surgery cannot be the ultimate answer, can we not stop the valve from “turning to stone” in the first place?
Here, we identify chipericumin D as a potent inhibitor of human aortic valve interstitial cell (hVIC) calcification, and we demonstrate its efficacy by directly binding to EGFR and suppressing the EGFR/PI3K/AKT signaling pathway. Chipericumin D, acting as a natural “lock” on EGFR, prevents its phosphorylation and the subsequent activation of the downstream PI3K/AKT cascade; while the activation of EGFR or AKT by specific agonists reverses these protective effects, confirming that chipericumin D halts the “stone-forming” process by silencing this specific signaling axis.
This work provides a new strategy based on natural product screening to identify anti-calcification agents and reveals the critical role of EGFR as a novel therapeutic target in CAVD. The work entitled “ Hypericum monogynum extract inhibits human aortic valve interstitial cell calcification by interfering with the EGFR/PI3K/AKT signaling pathway ” was published on Chinese Journal of Natural Medicines . (published on April 20, 2026).
Chinese Journal of Natural Medicines
Experimental study
Not applicable
Hypericum monogynum extract inhibits human aortic valve interstitial cell calcification by interfering with the EGFR/PI3K/AKT signaling pathway
20-Apr-2026