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Title: | Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)-(+)-Carvone Identifies a Novel Class of Sirtuin-1 Activators in a Murine Macrophage Cell Line | Authors: | Sousa, Cátia Neves, Bruno Miguel Leitão, Alcino Jorge Mendes, Alexandrina Ferreira |
Keywords: | aging; inflammation; monoterpene; NF- B; Sirtuin-1; Sirtuin-1 activating compound | Issue Date: | 4-Jul-2021 | Project: | POCI-01-0145-FEDER-CARTILFACTORY CENTRO-01-0145-FEDER-HealthyAging2020 POCI-01-0145-FEDER-028424 CENTRO-01-0145- FEDER-007440 UIDB/04539/2020 UIDP/04539/2020 PhD fellowship, SFRH/79600/2011 |
Serial title, monograph or event: | Biomedicines | Volume: | 9 | Issue: | 7 | Abstract: | The signaling pathways involved in age-related inflammation are increasingly recognized as targets for the development of preventive and therapeutic strategies. Our previous study elucidated the structure-activity relationship of monoterpene compounds derived from p-menthane as potential anti-inflammatory drugs and identified (S)-(+)-carvone as the most potent among the compounds tested. This study aims at identifying the molecular mechanism underlying the anti-inflammatory properties of (S)-(+)-carvone. The murine macrophage cell line, Raw 264.7, was stimulated with bacterial lipopolysaccharide (LPS) to simulate inflammation. Western blot was used to assess protein levels and post-translational modifications. The subcellular localization of NF-κB/p65 was visualized by immunocytochemistry. An in vitro fluorometric assay was used to measure Sirtuin-1 (SIRT1) activity. (S)-(+)-carvone inhibited LPS-induced JNK1 phosphorylation, but not that of p38 and ERK1/2 and also did not affect the phosphorylation and degradation of the NF-κB inhibitor, IκB-α. Accordingly, (S)-(+)-carvone did not affect LPS-induced phosphorylation of NF-κB/p65 on Ser536 and its nuclear translocation, but it significantly decreased LPS-induced IκB-α resynthesis, a NF-κB-dependent process, and NF-κB/p65 acetylation on lysine (Lys) 310. Deacetylation of that Lys residue is dependent on the activity of SIRT1, which was found to be increased by (S)-(+)-carvone, while its protein levels were unaffected. Taken together, these results show that (S)-(+)-carvone is a new SIRT1 activator with the potential to counteract the chronic low-grade inflammation characteristic of age-related diseases. | URI: | https://hdl.handle.net/10316/103760 | ISSN: | 2227-9059 | DOI: | 10.3390/biomedicines9070777 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais FFUC- Artigos em Revistas Internacionais I&D CIBB - Artigos em Revistas Internacionais |
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