{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lee JH"],"funding":["Chungnam National Hospital Research Fund (2021)","Basic Science Research Program","Ministry of Science, ICT and Future Planning","National Research Foundation of Korea"],"pagination":["641"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10934210"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(5)"],"pubmed_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 <i>TNFAPI3</i> 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."],"journal":["Nutrients"],"pubmed_title":["CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses."],"pmcid":["PMC10934210"],"funding_grant_id":["NRF-2022R1C1C1004346","RS-2022-00164733","NRF-2017R1A5A2015385"],"pubmed_authors":["Kim JM","Choi H","Han JM","Kim J","Lee YH","Choi YM","Song HY","Cho HD","Byun EB","Yuk JM","Ko YB","Kim WS","Lee JH","Cha GH"],"additional_accession":[]},"is_claimable":false,"name":"CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses.","description":"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 <i>TNFAPI3</i> 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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-26T03:25:03.109Z","creation":"2025-04-06T14:34:43.286Z"},"accession":"S-EPMC10934210","cross_references":{"pubmed":["38474770"],"doi":["10.3390/nu16050641"]}}