Geniposide alleviates atherosclerosis by regulating macrophage polarization via the FOS/MAPK signaling pathway.

Abstract

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-1β 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-1β 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.

• Authors: Zheng Jin, Junlong Li, Jianbin Pi, Qingmin Chu, Weichao Wei, Zhiyi Du, Lijin Qing, Xinjun Zhao, Wei Wu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 125 Pg. 110015 (May 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 32187958 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Cytokines
• Iridoids
• Proto-Oncogene Proteins c-fos
• RNA, Messenger
• geniposide

Topics

• Animals
• Atherosclerosis (drug therapy, pathology)
• Cytokines (metabolism)
• Diet, High-Fat
• Disease Progression
• Iridoids (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Macrophages (metabolism)
• Male
• Plaque, Atherosclerotic (drug therapy, pathology)
• Proto-Oncogene Proteins c-fos (genetics)
• RNA, Messenger (metabolism)
• Rabbits
• Signal Transduction (drug effects)