Geniposide alleviates atherosclerosis by regulating macrophage polarization via the FOS/MAPK signaling pathway.
OBJECTIVE To assess geniposide's effects in New Zealand rabbits with high fat diet induced atherosclerosis and to explore the underpinning mechanisms. MATERIALS AND METHODS Aorta histological changes were evaluated by intravenous ultrasound (IVUS) and H&E staining. Lipid accumulation in the aortic was quantified by Oil Red O staining. Then, RNA sequencing (RNA seq) was carried out for detecting differentially expressed genes in rabbit high fat diet induced atherosclerosis. The levels of the cytokines CRP, IL 1b and IL 10 were determined by ELISA. Protein levels of iNOS and Arg 1 were assessed by Western blot and immunohistochemical staining. The mRNA expression levels of NR4A1, CD14, FOS, IL1A, iNOS and Arg 1 were detected by quantitative real time PCR (qPCR) RESULTS Geniposide markedly reduced the degree of atherosclerotic lesions in aorta tissues. RNA seq and qPCR demonstrated that NR4A1, CD14, FOS and IL1A mRNA amounts were overtly increased in New Zealand rabbits with high fat diet induced atherosclerosis. Moreover, geniposide reduced iNOS (M1 phenotype) mRNA and protein amounts as well as IL 1b secretion, which were enhanced in New Zealand rabbits with high fat diet induced atherosclerosis. Besides, Arg 1 (M2 phenotype) mRNA and protein amounts were significantly increased after geniposide treatment, as well as IL 10 secretion. CONCLUSION These findings suggest that geniposide could inhibit the progression of and stabilize atherosclerotic plaques in rabbits by suppressing M1 macrophage polarization and promoting M2 polarization through the FOS/MAPK signaling pathway.
Biomedicine pharmacotherapy Biomedecine pharmacotherapie