Apigenin ameliorates atherosclerosis by inhibiting macrophage foam cell formation in ApoE^−/−mice fed a high fat diet

Background Apigenin is a bioactive flavonoid and widely found in herbs, fruits, and vegetables. Accumulated evidences have demonstrated the protective potential of apigenin on cardiovascular diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the therapeutic effects of apigenin on atherosclerosis in vivo and explore the potential mechanism. Methods ApoE^−/− mice were fed a high-fat diet (HFD) and supplemented with apigenin (20 mg/kg or 40 mg/kg) by gavage for 12 weeks. Oil Red O, hematoxylin and eosin staining (H&E), and Elastin Van Gieson (EVG) staining were performed to assess atherosclerotic plaque in ApoE^−/− mice. Commercial kits were used to measure the serum lipids, inflammatory cytokines and oxidants. Immunohistochemistry staining, immunofluorescent staining and Western blot were performed to assess PPARγ, LXRα, ABCA1, and ABCG1 expression. Results Apigenin obviously reduced lesion areas in both en-face aortas and aortic root in HFD fed ApoE^−/− mice. Apigenin also effectively ameliorated dyslipidemia, reduced inflammatory cytokines and oxidant levels in vivo. Immunofluorescent results showed that apigenin remarkably reduced macrophage foam cells in atherosclerotic plaque. Double immunofluorescent staining demonstrated high expression of ABCA1 and ABCG1. Moreover, apigenin also increased PPARγ and LXRα expression in atherosclerotic plaque. Conclusions Apigenin alleviated atherosclerosis development by inhibiting macrophage foam cell formation via PPARγ-LXRα-ABCA1/ABCG1 pathway.