Resveratrol Suppresses Severe Acute Pancreatitis‐Induced Microcirculation Disturbance through Targeting SIRT1‐FOXO1 Axis

Abstract

Background. Resveratrol (RSV), one of the SIRT1 agonists, has the ability of alleviating severe acute pancreatitis (SAP); however, the concrete protective mechanism remains unknown. It is noteworthy that microcirculation disturbance plays a vital role in SAP, and the SIRT1/FOX1 axis can regulate microcirculation. Therefore, this study is aimed at ascertaining what is the underlying mechanism of the protective effect of RSV on SAP, and whether it is associated with alleviating microcirculation disturbance by regulating the SIRT1/FOX1 axis. Method. The model of SAP was induced by retrograde injection of sodium taurodeoxycholate into the bile duct of the rats. The pancreatic wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α ratios; microcirculatory function; and SIRT1 activity were examined. ELISA was used to examine the serum level of lipase, amylase, hemorheology, ET, NO, TXB2, and 6-keto-PGF1α and the content of SIRT1, VEGF, Ang I, and Ang II in the pancreas. RT-PCR was used to examine the mRNA level of VEGF, Ang I, and Ang II. Western blotting was used to detect SIRT1, FOXO1, and acetyl-FOXO1. Immunoprecipitation was used to examine the interaction of SIRT1 and FOXO1. Results. Resveratrol can significantly decrease the expression of lipase, amylase, acetyl-FOXO1, VEGF, Ang II, ET, NO, TXB2, and 6-keto-PGF1α and the ratio of wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α by improving microcirculatory dysfunction and blood viscosity in SAP. Moreover, resveratrol can also promote the interaction of SIRT1 and FOXO1 and increase SIRT1 activity and the expression of SIRT1 and Ang I. The SIRT1 inhibitor, Sirtinol (EX527), obliviously reversed the effects of RSV on SAP. Conclusion. Resveratrol can protect rats against SAP, and its protective mechanism is associated with suppressing microcirculation disturbance through activating SIRT1-FOXO1 axis.

Phytochemicals with protective effects against acute pancreatitis: a review of recent literature

“…Furthermore, it can increase the interaction of SIRT1 and forkhead box protein O1 (FOXO1) with substantial decrease in acetyl-FOXO1 expression (Rong et al. 2021 ). In addition, resveratrol can inhibit the activation of NF-κB, PI3Ks/AKT, activator protein 1 (AP-1) and TNF-α, which are responsible for various inflammatory processes (Tsang et al.…”

Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways

“…SIRT1 also is closely associated with the mammalian forkhead transcription proteins [24,55,[193][194][195][196][197]. The induction of autophagy relies upon mammalian FOXO proteins of the O class that have an important relationship to neurodegenerative disorders [40,162,187,198,199].…”

“…In regard to SIRT1, SIRT1 activity leads to increased survival through inhibition of FoxO activity [5,14,[194][195][196]. Yet, FoxOs also can bind to the SIRT1 promoter region to alter forkhead transcription [206].…”

Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm

“…Phosphorylation or acetylation of FoxOs can change the binding of the C-terminal basic region to DNA to inhibit FoxO transcriptional activity [48,152,199,248]. FoxOs are intimately connected circadian rhythm since they are linked to SIRT1 [4,34,48,85,[248][249][250][251][252]. For example, insulin-phosphatidylinositol 3-kinase (PI3K) signaling that occurs in the liver is overseen by FoxO3 control of circadian rhythmicity through modulation of Clock.…”

“…In regard to SIRT1, blockade of the activity of FoxOs by SIRT1 can promote cell survival [19,67,[249][250][251]. However, FoxOs can attach to the SIRT1 promoter region to further change forkhead transcription [181].…”