CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses
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.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
---|---|
Enthalten in: |
Nutrients - 16(2024), 5 vom: 25. Feb. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Lee, Jae-Hyung [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 14.03.2024 Date Revised 15.03.2024 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.3390/nu16050641 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM369644891 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM369644891 | ||
003 | DE-627 | ||
005 | 20240315233907.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240313s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/nu16050641 |2 doi | |
028 | 5 | 2 | |a pubmed24n1330.xml |
035 | |a (DE-627)NLM369644891 | ||
035 | |a (NLM)38474770 | ||
035 | |a (PII)641 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Lee, Jae-Hyung |e verfasserin |4 aut | |
245 | 1 | 0 | |a CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 14.03.2024 | ||
500 | |a Date Revised 15.03.2024 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a CM1 | |
650 | 4 | |a TNFAIP3 | |
650 | 4 | |a Toll-like receptor 4 | |
650 | 4 | |a inflammation | |
650 | 4 | |a sepsis | |
650 | 4 | |a sirtuin 1 | |
650 | 7 | |a Sirtuin 1 |2 NLM | |
650 | 7 | |a EC 3.5.1.- |2 NLM | |
650 | 7 | |a Toll-Like Receptor 4 |2 NLM | |
650 | 7 | |a chrysin |2 NLM | |
650 | 7 | |a 3CN01F5ZJ5 |2 NLM | |
650 | 7 | |a Lipopolysaccharides |2 NLM | |
650 | 7 | |a NF-kappa B |2 NLM | |
650 | 7 | |a Endotoxins |2 NLM | |
650 | 7 | |a Cytokines |2 NLM | |
650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
650 | 7 | |a Flavonoids |2 NLM | |
700 | 1 | |a Ko, Young-Bok |e verfasserin |4 aut | |
700 | 1 | |a Choi, Yong-Min |e verfasserin |4 aut | |
700 | 1 | |a Kim, Jinju |e verfasserin |4 aut | |
700 | 1 | |a Cho, Hwan-Doo |e verfasserin |4 aut | |
700 | 1 | |a Choi, Hyeonil |e verfasserin |4 aut | |
700 | 1 | |a Song, Ha-Yeon |e verfasserin |4 aut | |
700 | 1 | |a Han, Jeong-Moo |e verfasserin |4 aut | |
700 | 1 | |a Cha, Guang-Ho |e verfasserin |4 aut | |
700 | 1 | |a Lee, Young-Ha |e verfasserin |4 aut | |
700 | 1 | |a Kim, Jin-Man |e verfasserin |4 aut | |
700 | 1 | |a Kim, Woo-Sik |e verfasserin |4 aut | |
700 | 1 | |a Byun, Eui-Baek |e verfasserin |4 aut | |
700 | 1 | |a Yuk, Jae-Min |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Nutrients |d 2009 |g 16(2024), 5 vom: 25. Feb. |w (DE-627)NLM206140738 |x 2072-6643 |7 nnns |
773 | 1 | 8 | |g volume:16 |g year:2024 |g number:5 |g day:25 |g month:02 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/nu16050641 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 16 |j 2024 |e 5 |b 25 |c 02 |