Anti-atherosclerotic effects of Thymus quinquecostatus Celak extracts in vitro: Regulating macrophage foaming and endothelial cell injury.

Atherosclerosis (AS) serves as a critical pathological basis for cardiovascular diseases (CVDs), imposing significant global healthcare and economic burdens. Thymus quinquecostatus Celak (TQC), a versatile natural plant with medicinal, edible, ornamental, and environmental protection applications, has demonstrated cardiovascular protective effects. However, the potential anti-atherosclerotic mechanisms of TQC have not been reported. This study aimed to screen and compare extracts of TQC against AS, and reveal potential active molecules and mechanisms. The fingerprints of five extracts in TQC were established by HPLC-UV. The anti-AS potential of each extract of TQC was evaluated through a macrophage foaming model, identifying TQC ethanol extract (TEE) as the most effective extract in reducing lipid accumulation, suppressing inflammation, improving oxidative stress and mitophagy. Subsequently, the capacity of TEE to inhibit endothelial dysfunction was validated in an endothelial cell injury model, including ameliorating inflammation, cell adhesion, oxidative stress and mitophagy. Mechanistic investigations revealed that TEE's dual-cell protective effects involve the modulation of the Nrf2/HO-1/PINK1/Parkin signaling axis. Molecular docking studies further identified scutellarein as the most potent compound among those identified by TEE, exhibiting the strongest binding interactions with key therapeutic targets. Collectively, this study provides a theoretical foundation for developing TQC as a cardioprotective therapeutic candidate, offering references for its pharmacological investigations.