Modafinil ameliorated pancreatic injury and inflammation through upregulating SNIP1

Abstract

Acute pancreatitis (AP) is the inflammatory response of the exocrine pancreas to various causes. Modafinil has significant anti-inflammation and anti-oxidation effects. No experiment has assessed the effects of modafinil on AP. Thus, the study aims to study the effects of modafinil on AP and its potential mechanism in vivo and vitro. 5% sodium taurocholate was retrograde injected into pancreatic duct to establish AP rat model. The severity of AP was detected by H&E staining, serum amylase and lipase levels. The inflammation, oxidative stress and apoptosis were detected separately by ELISA, MDA and SOD kits, tunnel staining and Western blotting in rats. Besides, SNIP1 expression was analyzed by qPCR and Western blotting. In vivo, AR42J cells were stimulated by cerulein and lipopolysaccharide to establish AP cell model. Flow cytometry examined cell apoptosis. After the plasmids silencing SNIP1 were transfected into AP cells, the inhibitory effects of modafinil on inflammation, oxidative stress and apoptosis were significantly reversed. The results indicated that modafinil showed significant curative and therapeutic effects by regulating SNIP1 levels.

Modafinil lightens apoptosis and inflammatory response in hepatic ischemia‐reperfusion injury through inactivation of TLR9/Myd88/p38 signaling

“…Emerging reports have underlined the potential therapeutic potential of MOD in a variety of disorders due to the beneficial pharmacological properties it produces (Kowsari et al, 2021; Wu et al, 2020). Importantly, recent evidence has valued MOD as a protective agent in IRI.…”

“…Modafinil (MOD; 2-[(diphenylmethyl) sulfinyl] acetamide; brand name Provigil in the United States) is a wakefulness enhancer that has been approved by the United States Food and Drug Administration as a psychoactive drug in the treatment of narcolepsy (Kredlow et al, 2019). In addition to these indications, MOD also possesses anti-inflammatory, antifibrotic, antioxidative, and neuroprotective activities, exhibiting ever-expanding uses in nonalcoholic liver disease (Choi et al, 2021), acute pancreatitis (Wu et al, 2020) and ischemic brain injuries (Abbasi et al, 2019). In particular, MOD has been supported to protect against IRI in diverse organs, including intestine (Kamel et al, 2020), and testis (Yousefi-Manesh et al, 2019).…”

The clinical utilization of SNIP1 and its pathophysiological mechanisms in disease

“…Moreover, there is evidence indicating a significant decrease in SNIP1 levels in peripheral blood mononuclear cells of IBD patients [ 36 ]. Additionally, SNIP1 has been found to impede the recruitment of Smad4 into the coactivator CBP/P300 and TGF-β downstream genes to alleviate acute pancreas injury [ 37 ]. Furthermore, overexpression SNIP1 reduced the expression of TNF-α and IL-6, alleviated ECM degradation, reduced the phosphorylation levels of p65 and IκBα, and alleviated osteoarthritis(OA) inflammation [ 38 ].…”

“…Modafinil treatment in an AP rat model significantly restored the expression of SNIP1, resulting in a reduction in inflammation, oxidative stress, and apoptosis. [ 37 ] Table2 (supplemental). SNIP1 Associated with Inflammatory Diseases Diseases Methods Markers Conclusion Reference Osteoarthritis (OA) The expression of SNIP1 was confirmed by clinical trials and animal experiments.…”