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- Title
CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses.
- Authors
Lee, Jae-Hyung; Ko, Young-Bok; Choi, Yong-Min; Kim, Jinju; Cho, Hwan-Doo; Choi, Hyeonil; Song, Ha-Yeon; Han, Jeong-Moo; Cha, Guang-Ho; Lee, Young-Ha; Kim, Jin-Man; Kim, Woo-Sik; Byun, Eui-Baek; Yuk, Jae-Min
- Abstract
Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.
- Subjects
INFLAMMATION prevention; IN vitro studies; MITOGEN-activated protein kinases; NF-kappa B; CARRIER proteins; RESEARCH funding; FLAVONOIDS; IN vivo studies; TOLL-like receptors; CELLULAR signal transduction; SEPTIC shock; MICE; ANIMAL experimentation; TRANSFERASES; CYTOKINES; DISEASE susceptibility; ENDOTOXINS
- Publication
Nutrients, 2024, Vol 16, Issue 5, p641
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu16050641