PMID- 36708976 OWN - NLM STAT- MEDLINE DCOM- 20230214 LR - 20230214 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 942 DP - 2023 Mar 5 TI - Myricetin ameliorates experimental autoimmune myocarditis in mice by modulating immune response and inhibiting MCP-1 expression. PG - 175549 LID - S0014-2999(23)00060-2 [pii] LID - 10.1016/j.ejphar.2023.175549 [doi] AB - Myocarditis is defined as an inflammatory disease of the myocardium, and the autoimmune response specific to myocardium plays an important role in chronic myocarditis. Inhibiting myocardial-specific autoimmune response and inflammation is crucial to treat myocarditis. Myricetin is a plant-derived flavonoid in nature which has potent anti-inflammatory and cardiovascular protective properties. However, the pharmacological effect of myricetin in autoimmune myocarditis is undefined. It is necessary to investigate the role and potential mechanisms of myricetin in autoimmune myocarditis. Therefore, purified cardiac myosin was subcutaneously injected to mice to establish the experimental autoimmune myocarditis (EAM) model. Myricetin was solubilized in normal saline and administered everyday by gavage from the day of immunization. After 21 days of treatment, it was found that myricetin significantly alleviated myocardial injury in EAM mice. The serum anti-cardiac myosin antibody, immunoglobulin (Ig) G, IgM levels and the proportion of T helper 17 (Th17) cells were decreased and the proportion of regulatory T (Treg) cells was increased with the treatment of myricetin in EAM mice. The myosin-specific T cell proliferation was inhibited by myricetin. Meanwhile, myricetin suppressed the expressions of monocyte chemoattractant protein-1 (MCP-1), phospho (p)-p65, p-c-Jun and Act1/TRAF6/TAK1 in H9C2 cells and myocardial tissues of EAM mice. These results revealed that myricetin inhibited the autoimmune response specific to myocardium and the expression of MCP-1 in cardiomyocytes, which suggested that myricetin ameliorated autoimmune myocarditis by modulating immune response and the expression of MCP-1. Therefore, myricetin may be a promising therapeutic strategy for autoimmune myocarditis. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Nie, Na AU - Nie N AD - Department of Clinical Laboratory, Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Li, Zhuolun AU - Li Z AD - Henan Engineering Research Center of Clinical Mass Spectrometry for Precision Medicine, Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Li, Wenhuan AU - Li W AD - BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, China. FAU - Huang, Xiao AU - Huang X AD - Department of Clinical Laboratory, Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Jiang, Zuli AU - Jiang Z AD - Department of Clinical Laboratory, Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. FAU - Shen, Yan AU - Shen Y AD - Department of Clinical Laboratory, Key Clinical Laboratory of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: shenyan62687@126.com. LA - eng PT - Journal Article DEP - 20230125 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Chemokine CCL2) RN - 0 (Flavonoids) RN - EC 3.6.4.1 (Myosins) RN - 76XC01FTOJ (myricetin) RN - 0 (Ccl2 protein, mouse) SB - IM MH - Animals MH - Mice MH - *Autoimmune Diseases/drug therapy MH - Chemokine CCL2/metabolism MH - Disease Models, Animal MH - Flavonoids/pharmacology/therapeutic use/metabolism MH - Immunity MH - *Myocarditis/drug therapy/metabolism MH - Myocardium/metabolism MH - Myosins/metabolism OTO - NOTNLM OT - Act1/ TRAF6/ TAK1 pathway OT - Autoimmune myocarditis OT - Immune response OT - Monocyte chemoattractant protein-1 OT - Myricetin COIS- Declaration of competing interest The authors declare that they have no conflicts of interest in relation to the contents of this article. EDAT- 2023/01/29 06:00 MHDA- 2023/02/14 06:00 CRDT- 2023/01/28 19:27 PHST- 2022/09/06 00:00 [received] PHST- 2023/01/24 00:00 [revised] PHST- 2023/01/24 00:00 [accepted] PHST- 2023/01/29 06:00 [pubmed] PHST- 2023/02/14 06:00 [medline] PHST- 2023/01/28 19:27 [entrez] AID - S0014-2999(23)00060-2 [pii] AID - 10.1016/j.ejphar.2023.175549 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Mar 5;942:175549. doi: 10.1016/j.ejphar.2023.175549. Epub 2023 Jan 25.