Berberine Attenuates Cerulein-Induced Acute Pancreatitis by Modulating Nrf2/NOX2 Signaling Pathway via AMPK Activation.

Autor: Bansod SP; Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India.; Division of Oncology, Department of Internal Medicine, Barnes-Jewish Hospital and the Alvin J. Siteman Comprehensive Cancer Center, Washington University School of Medicine, St. Louis, Missouri, USA., Saifi MA; Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India., Chilvery S; Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India., Doijad N; Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India., Godugu C; Department of Biological Sciences (Regulatory Toxicology), National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, India.
Jazyk: angličtina
Zdroj: Environmental toxicology [Environ Toxicol] 2024 Dec 26. Date of Electronic Publication: 2024 Dec 26.
DOI: 10.1002/tox.24468
Abstrakt: AMP-activated protein kinase (AMPK) is the master regulator of cellular energy which gets activated during energy stress and restores tissue homeostasis. AMPK is widely expressed in the pancreas and is involved in protein synthesis. In cerulein-induced acute pancreatitis (AP), diminished AMPK activity in the pancreatic tissue may be associated with pancreatic inflammation and oxidative stress. Our results demonstrated that berberine (BR) treatment produced significant decrease in plasma amylase and lipase levels and improved histopathological features in AP mice model. Myeloperoxidase (MPO) activity indicated that BR suppressed the infiltration of neutrophils in pancreas. BR treatment markedly decreased the levels of proinflammatory cytokines including interleukins (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) via inhibition of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression. In addition, BR activates the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and inhibits cerulein-induced oxidative-nitrosative stress. Mechanistically, we found inhibition of AMPK activity in cerulein-induced AP, while BR-treated animals showed marked increase in the AMPK expression. Together, our study indicated that BR-mediated AMPK activation in pancreatic tissues demonstrated attenuation of cerulein-induced oxidative stress and inflammation. Based on our observations, further exploration of this promising natural product against AP and associated complications may lead to promising therapeutic options.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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