Corilagin Alleviates Atherosclerosis by Inhibiting NLRP3 Inflammasome Activation Via the Olfr2 Signaling Pathway and

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 May 28

PMID 38803504

Authors

Jinqian Mao

Yunfei Chen

Qiushuo Zong

Cuiling Liu

Jiao Xie

Yujie Wang

David Fisher

Nguyen Thi Thu Hien

Khrystyna Pronyuk

Erkin Musabaev

Yiqing Li

Lei Zhao

Yiping Dang

Affiliations

Soon will be listed here.

Abstract

Introduction: Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production.

Methods: To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein.

Results: The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway.

Discussion: Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.

References

Nandini H, Naik P . Action of corilagin on hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats. Chem Biol Interact. 2018; 299:186-193. DOI: 10.1016/j.cbi.2018.12.012. View

Duan W, Yu Y, Zhang L . Antiatherogenic effects of phyllanthus emblica associated with corilagin and its analogue. Yakugaku Zasshi. 2005; 125(7):587-91. DOI: 10.1248/yakushi.125.587. View

Li M, Wang Z, Fang L, Cheng S, Wang X, Liu N . Programmed cell death in atherosclerosis and vascular calcification. Cell Death Dis. 2022; 13(5):467. PMC: 9117271. DOI: 10.1038/s41419-022-04923-5. View

Christgen S, Place D, Kanneganti T . Toward targeting inflammasomes: insights into their regulation and activation. Cell Res. 2020; 30(4):315-327. PMC: 7118104. DOI: 10.1038/s41422-020-0295-8. View

Orecchioni M, Kobiyama K, Winkels H, Ghosheh Y, McArdle S, Mikulski Z . Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production. Science. 2022; 375(6577):214-221. PMC: 9744443. DOI: 10.1126/science.abg3067. View

Weber C, Habenicht A, von Hundelshausen P . Novel mechanisms and therapeutic targets in atherosclerosis: inflammation and beyond. Eur Heart J. 2023; 44(29):2672-2681. DOI: 10.1093/eurheartj/ehad304. View

Lee J, Zhao L, Hwang D . Modulation of pattern recognition receptor-mediated inflammation and risk of chronic diseases by dietary fatty acids. Nutr Rev. 2010; 68(1):38-61. DOI: 10.1111/j.1753-4887.2009.00259.x. View

Back M, Yurdagul Jr A, Tabas I, Oorni K, Kovanen P . Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities. Nat Rev Cardiol. 2019; 16(7):389-406. PMC: 6727648. DOI: 10.1038/s41569-019-0169-2. View

Buldak L . Cardiovascular Diseases-A Focus on Atherosclerosis, Its Prophylaxis, Complications and Recent Advancements in Therapies. Int J Mol Sci. 2022; 23(9). PMC: 9103939. DOI: 10.3390/ijms23094695. View

10.

Yang S, Yuan H, Hao Y, Ren Z, Qu S, Liu L . Macrophage polarization in atherosclerosis. Clin Chim Acta. 2019; 501:142-146. DOI: 10.1016/j.cca.2019.10.034. View

11.

Paramel Varghese G, Folkersen L, Strawbridge R, Halvorsen B, Yndestad A, Ranheim T . NLRP3 Inflammasome Expression and Activation in Human Atherosclerosis. J Am Heart Assoc. 2016; 5(5). PMC: 4889178. DOI: 10.1161/JAHA.115.003031. View

12.

Yamada H, Nagao K, Dokei K, Kasai Y, Michihata N . Total synthesis of (-)-corilagin. J Am Chem Soc. 2008; 130(24):7566-7. DOI: 10.1021/ja803111z. View

13.

Zhaolin Z, Guohua L, Shiyuan W, Zuo W . Role of pyroptosis in cardiovascular disease. Cell Prolif. 2018; 52(2):e12563. PMC: 6496801. DOI: 10.1111/cpr.12563. View

14.

Liaqat A, Asad M, Shoukat F, Khan A . A Spotlight on the Underlying Activation Mechanisms of the NLRP3 Inflammasome and its Role in Atherosclerosis: A Review. Inflammation. 2020; 43(6):2011-2020. DOI: 10.1007/s10753-020-01290-1. View

15.

Li W, Yang K, Li B, Wang Y, Liu J, Chen D . Corilagin alleviates intestinal ischemia/reperfusion-induced intestinal and lung injury in mice inhibiting NLRP3 inflammasome activation and pyroptosis. Front Pharmacol. 2022; 13:1060104. PMC: 9727192. DOI: 10.3389/fphar.2022.1060104. View

16.

Frostegard J . Immunity, atherosclerosis and cardiovascular disease. BMC Med. 2013; 11:117. PMC: 3658954. DOI: 10.1186/1741-7015-11-117. View

17.

He B, Chen D, Zhang X, Yang R, Yang Y, Chen P . Antiatherosclerotic effects of corilagin via suppression of the LOX-1/MyD88/NF-κB signaling pathway in vivo and in vitro. J Nat Med. 2022; 76(2):389-401. DOI: 10.1007/s11418-021-01594-y. View

18.

Lee J, Hwang D . The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. Mol Cells. 2006; 21(2):174-85. View

19.

Christgen S, Kanneganti T . Inflammasomes and the fine line between defense and disease. Curr Opin Immunol. 2019; 62:39-44. PMC: 7067632. DOI: 10.1016/j.coi.2019.11.007. View

20.

Grebe A, Hoss F, Latz E . NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. Circ Res. 2018; 122(12):1722-1740. DOI: 10.1161/CIRCRESAHA.118.311362. View