To elucidate the possible mechanism of Jiawei Erzhi pill (, JWEZP) in the treatment of atherosclerosis (AS). The chemical constituents of JWEZP were identified using ultra-performance liquid chromatog Show more
To elucidate the possible mechanism of Jiawei Erzhi pill (, JWEZP) in the treatment of atherosclerosis (AS). The chemical constituents of JWEZP were identified using ultra-performance liquid chromatography-mass spectrometry. A high-fat diet (HFD) was used to establish AS models in ApoE We identified 46 active compounds in JWEZP. Mice in the JWEZP group had lower body weights and serum cholesterol levels compared to HFD mice. The results of Hematoxylin-Eosin and Oil Red O staining showed that JWEZP alleviated AS. Masson staining showed that JWEZP improved the stability of atherosclerotic plaques. In addition, JWEZP-treated mice had lower levels of reactive oxygen species (ROS) in thoracic aortic tissue according to ROS fluorescence staining. The ELISA results showed that JWEZP decreased the levels of iron, lipid peroxide, malondialdehyde and nicotinamide adenine dinucleotide phosphate and increased the levels of glutathione (GSH) and GSH-PX in the thoracic aortic tissues of mice. The expression of glutathione peroxidase 4 in the thoracic aorta of mice in the JWEZP group was upregulated in the results of the immunofluorescence assay. Network pharmacology results indicated that the action mechanisms of JWEZP-mediated inhibition of ferroptosis were closely related to the p53, mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) signaling pathways. RT-qPCR and Western blotting results demonstrated that JWEZP inhibited the p53 and MAPK pathways, and activated the PI3K/Akt pathway to regulate ferroptosis. JWEZP improved AS by inhibiting ferroptosis. The study provides a scientific basis for further research and validation of JWEZP as a potential therapeutic for AS. Show less