Paeonol from Paeonia lactiflora attenuates calcification of aortic valvular interstitial cell by inhibiting activation of redox-sensitive NFκB/AKT/ERK1/2 pathway

Calcific aortic valve disease (CAVD) is a life-threatening cardiovascular condition without effective pharmacological treatments. Paeonol, a bioactive compound from the roots of Paeonia lactiflora, is known for its anti-inflammatory, antioxidant, and anti-atherosclerotic properties. While it has shown benefits in treating several cardiovascular conditions, its role in CAVD remains unexplored, requiring further investigation. This study explores paeonol's potential to inhibit calcification in porcine valve interstitial cells (VICs) and to elucidate the underlying mechanism. Calcification was induced using a pro-calcifying medium (PCM), and the anti-calcification effects of paeonol were evaluated. Paeonol significantly reduced level of calcification and its markers such as RUNX2, osteopontin, and BMP2. It also lowered reactive oxygen species levels, thereby reducing oxidative stress, which is known to activate several calcification pathways. Paeonol inhibited these pathways by reducing phosphorylation of NF kappa B, AKT, and ERK1/2, thereby preventing their activation and suggesting its potential as a therapeutic agent to mitigate CAVD progression.