Dual modulation of lipid-lowering and anti-inflammatory effects of Thymus quinquecostatus Celak. ethanol extract on atherosclerosis: integration of UPLC-Q-TOF-MS/MS, in silico, in vivo, and in vitro studies.

BACKGROUND: Atherosclerosis (AS) is a chronic progressive disease characterized primarily by lipid deposition and inflammation. Thymus quinquecostatus Celak. (TQC), widely used in health teas and food preparations, possesses anti-inflammatory, antithrombotic, and anti-ischemic properties, showing potential as a functional food with anti-atherosclerotic effects. The aim of this study was to investigate the effects and mechanisms of TQC ethanol extract (TEE) on AS. RESULTS: Ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS/MS) analysis identified 102 chemical components in TEE, with flavonoids and phenolic acids as the main constituents. In vivo and in vitro studies revealed that TEE effectively inhibited plaque progression and lipid accumulation, improved serum lipid profiles and fatty liver, and decreased pro-inflammatory cytokine levels in both serum and plaque macrophages. Network pharmacology indicated the importance of key targets, including phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), protein kinase B (AKT), and interleukin-6 (IL-6), and core signaling pathways, such as phosphoinositide 3-kinase-AKT (PI3K-AKT) and mitogen-activated protein kinase (MAPK). Molecular docking demonstrated strong binding affinity of sclareol, scutellarein, and kaempferol to the critical targets. Immunofluorescence, plasmid transfection, immunohistochemistry, and Western blotting demonstrated that TEE effectively alleviated lipid accumulation and inflammation in AS by promoting autophagy and cholesterol efflux, which might be attributable to suppression of the PI3K/AKT/mechanistic target of rapamycin (mTOR) and p38 MAPK pathways. Moreover, the PI3K inhibitor LY294002 enhanced the modulatory effects of TEE on autophagy and cholesterol efflux proteins. CONCLUSION: This study shows the potential of TEE as a functional food for lipid-lowering and anti-inflammatory strategies in cases of AS. © 2026 Society of Chemical Industry.