Galangin ameliorates severe acute pancreatitis in mice by activating the nuclear factor E2-related factor 2/heme oxygenase 1 pathway - 13/11/21
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Abstract |
Acute pancreatitis (AP) is a common serious acute condition of the digestive system that remains a clinical challenge. Severe acute pancreatitis (SAP) in particular is characterized by high morbidity and mortality. The present study was designed to investigate the protective effect of Galangin (Gal), a natural flavonol obtained from lesser galangal, on L-arginine-induced SAP in mice and in AR42J cells. Amylase and lipase activities were measured and the histopathology of the pancreas, lung, and kidney was evaluated. Inflammation and oxidative stress were assessed using ELISA, western blotting, RT-PCR, and immunohistochemistry. Gal was shown to reduce proinflammatory cytokine production and reactive oxygen species (ROS) generation in vivo and in vitro. L-arginine treatment reduced the expression of components of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and the downstream protein heme oxygenase-1 (HO-1) in mice, whereas Gal increased their expression. Furthermore, the Nrf2/HO-1 pathway inhibitor brusatol prevented the anti-inflammatory and antioxidant effects of Gal in mice with SAP. Taken together, our results imply that Gal has protective effects in L-arginine-induced SAP that are induced by the upregulation of the Nrf2/HO-1 pathway, which has anti-inflammatory and antioxidant effects. Thus, Gal may represent a promising treatment for SAP.
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Highlights |
• | Gal suppresses inflammation and oxidative stress in mice with SAP. |
• | Gal reduces pancreatic acinar cells oxidative stress induced by L-Arginine. |
• | Gal alleviates SAP associated lung and kidney injury in mice. |
• | The protective effect of Gal in mice with SAP was depended on Nrf2/HO-1 pathway. |
Abbreviations : AP, SAP, Gal, ROS, Nrf2, HO-1, Keap1, DMEM, GSH, MDA, SOD, 4-HNE, GPX4, ACSL4, Tnfa, Il18, Mcp1, Cxcl10, PBS, ELISA, H&E, IHC, IF, RT, ANOVA, NF-κB
Keywords : Galangin, Acute pancreatitis, Inflammation, Oxidative stress, Nuclear factor E2-related factor 2
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Vol 144
Article 112293- décembre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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