Artemisia absinthium L. Extract Targeting the JAK2/STAT3 Pathway to Ameliorate Atherosclerosis

Artemisia absinthium L. contributes to ecological stabilization in arid regions through its deep root system for sand fixation and soil microenvironment modulation, thereby effectively mitigating desertification. Total terpenoids have been extracted from A. absinthium (AATP) and found to have antioxidant and anti-inflammatory activities. Terpenoids are a class of natural products derived from methyl hydroxypropanoic acid, for which their structural units consist of multiple isoprene (C5) units. They are one of the largest and most structurally diverse classes of natural compounds. However, there are still large gaps in knowledge regarding their exact biological activities and effects. Atherosclerosis (AS) is a prevalent cardiovascular disease marked by the chronic inflammation of the vascular system, and lipid metabolism plays a key role in its pathogenesis. This study determined the extraction and purification processes of AATP through single-factor experiments and response surface optimization methods. The purity of AATP was increased from 20.85% ± 0.94 before purification to 52.21% ± 0.75, which is 2.5 times higher than before purification. Studies have shown that the total terpenoids of A. absinthium significantly reduced four indices of serum lipids in atherosclerosis (AS) rats, thereby promoting lipid metabolism, inhibiting inflammatory processes, and hindering aortic wall thickening and hepatic fat accumulation. It is known from network pharmacology studies that AATP regulates the Janus kinase/signal transducer (JAK/STAT) signaling axis. Molecular docking studies have indicated that the active component of AATP effectively binds to Janus kinase (JAK2) and signal transducer (STAT3) target proteins. The results indicate that AATP can inhibit the release of pro-inflammatory mediators (such as reactive oxygen species (ROS)) in LPS-induced RAW264.7 macrophages. It also inhibits the M1 polarization of RAW264.7 macrophages. Protein immunoblotting analysis revealed that it significantly reduces the phosphorylation levels of Janus kinase (JAK2) and the signal transducer and activator of transcription 3 (STAT3). Research indicates that the active components in A. absinthium may exert anti-atherosclerotic effects by regulating lipid metabolism and inhibiting inflammatory responses. It holds potential value for development as a functional food or drug for the prevention and treatment of atherosclerosis.