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Biomed Pharmacother ; 144: 112293, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34634559

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.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Flavonoids/pharmacology , Heme Oxygenase (Decyclizing)/metabolism , Heme Oxygenase-1/metabolism , Membrane Proteins/metabolism , NF-E2-Related Factor 2/metabolism , Pancreas/drug effects , Pancreatitis/prevention & control , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Acute Kidney Injury/prevention & control , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Acute Lung Injury/prevention & control , Animals , Cell Line , Disease Models, Animal , Inflammation Mediators/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Mice, Inbred C57BL , Oxidative Stress , Pancreas/enzymology , Pancreas/pathology , Pancreatitis/enzymology , Pancreatitis/pathology , Rats , Severity of Illness Index , Signal Transduction
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