A novel resveratrol analog upregulates sirtuin 1 and inhibits inflammatory cell infiltration in acute pancreatitis.
Acta Pharmacol Sin
; 43(5): 1264-1273, 2022 May.
Article
em En
| MEDLINE
| ID: mdl-34363008
ABSTRACT
Acute pancreatitis (AP), an inflammatory disorder of the pancreas, is a complicated disease without specific drug therapy. (R)-4,6-dimethoxy-3-(4-methoxy phenyl)-2,3-dihydro-1H-indanone [(R)-TML104] is a synthesized analog of the natural product resveratrol sesquiterpenes (±) -isopaucifloral F. This study aimed to investigate the effect and underlying mechanism of (R)-TML104 on AP. The experimental AP model was induced by caerulein hyperstimulation in BALB/c mice. (R)-TML104 markedly attenuated caerulein-induced AP, as evidenced by decreased pancreatic edema, serum amylase levels, serum lipase levels, and pancreatic myeloperoxidase activity. In addition, (R)-TML104 significantly inhibited the expression of pancreatic chemokines C-C motif chemokine ligand 2 and macrophage inflammatory protein-2 and the infiltration of neutrophils and macrophages. Mechanistically, (R)-TML104 activated AMP-activated protein kinase and induced sirtuin 1 (SIRT1) expression. (R)-TML104 treatment markedly induced the SIRT1-signal transducer and activator of transcription 3 (STAT3) interaction and reduced acetylation of STAT3, thus inhibiting the inflammatory response mediated by the interleukin 6-STAT3 pathway. The effect of (R)-TML104 on SIRT1-STAT3 interaction was reversed by treatment with a SIRT1 inhibitor selisistat (EX527). Together, our findings indicate that (R)-TML104 alleviates experimental pancreatitis by reducing the infiltration of inflammatory cells through modulating SIRT1.
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Base de dados:
MEDLINE
Assunto principal:
Pancreatite
/
Ceruletídeo
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article