SRT1720 ameliorates sodium taurocholate-induced severe acute pancreatitis in rats by suppressing NF-κB signalling

• Published in: Biomedicine & pharmacotherapy 2018-12, Vol.108, p.50-57
• Main Authors: Shi, Chenyuan, Hou, Chaoqun, Zhu, Xiaole, Huang, Dongya, Peng, Yunpeng, Tu, Min, Li, Qiang, Miao, Yi
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Heterocyclic Compounds, 4 or More Rings - chemistry; Heterocyclic Compounds, 4 or More Rings - pharmacology; Heterocyclic Compounds, 4 or More Rings - therapeutic use; Interleukin-6 - blood; Male; NF-kappa B - metabolism; NF-κB pathway; Pancreas - drug effects; Pancreas - pathology; Pancreatitis - blood; Pancreatitis - chemically induced; Pancreatitis - drug therapy; Pancreatitis - metabolism; Rats, Sprague-Dawley; Severe acute pancreatitis; Signal Transduction; SIRT1; Sirtuin 1 - metabolism; SRT1720; Taurocholic Acid; Tumor Necrosis Factor-alpha - blood
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.09.035

The mechanism of SRT1720. In sodium taurocholate-induced acute pancreatitis, SRT1720 reduces inflammatory reaction by suppressing NF-κB signalling. SIRT1 was over-expressed after SRT1720 injection. Then followed by the down-regulation of p65 and up-regulation of IκBα, in addition, p-P65 decreased the expression. The suppression of NF-κB signalling leads to a decrease in proinflammatory cytokines such as IL-6 and TNF-α released by inflammatory cells, resulting in a reduction in inflammation. [Display omitted] •SRT1720 is a SIRT1 activator that exerts multiple pharmacological activities.•SIRT1 expression level is impaired in rats with severe acute pancreatitis (SAP).•SRT1720 protects rats from sodium taurocholate-induced SAP.•SRT1720 suppresses the NF-κB signalling pathway in rat model of SAP.•SIRT1 activators may represent a new class of therapeutics for SAP. Severe acute pancreatitis (SAP) is a medical emergency that is often associated with multiple organ failure and high mortality. Although an SAP diagnosis requires prompt treatment, therapeutic options remain limited. SRT1720 is a newly formulatedSIRT1 activator that exerts multiple pharmacological activities with beneficial health effects. However, its potential as an SAP treatment has not been explored. The current study assessed the effect of SRT1720 on a rat model of sodium taurocholate-induced SAP and explored the underlying mechanism. SAP was induced in rats by retrograde injection of a 3.5% sodium taurocholate solution (1 ml/kg) in the biliopancreatic duct. SRT1720 (5 mg/kg) was administered intraperitoneally after sodium taurocholate exposure. Serum samples were analysed for inflammatory cytokine levels and select enzymatic activities using the enzyme-linked immunosorbent assay and commercial enzyme activity assay kits, respectively; protein expression levels were evaluated by western blotting; mRNA levels of biomarkers were determined by quantitative real-time PCR; histopathological changes were analysed by haematoxylin and eosin staining and immunohistochemistry.SRT1720 treatment significantly reduced serum amylase, lipase, pancreatic histological scores, proinflammatory cytokine (TNF-α and IL-6) levels, and expression of NF-κB and p65 in sodium taurocholate-induced SAP rats. Importantly, the treatment stimulated SIRT1 and IκBα levels in pancreatic tissue. Our data suggest that SRT1720 protects rats from sodium taurocholate-induced SAP by suppressing the NF-κB signalling pathway.