• Toxicol. Appl. Pharmacol. · Sep 2020

    Berberine attenuates severity of chronic pancreatitis and fibrosis via AMPK-mediated inhibition of TGF-β1/Smad signaling and M2 polarization.

    • Sapana Bansod, Nandkumar Doijad, and Chandraiah Godugu.
    • Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India.
    • Toxicol. Appl. Pharmacol. 2020 Sep 15; 403: 115162.

    AbstractBerberine (BR) acts as an AMP-activated protein kinase (AMPK) activator which possesses antioxidant and anti-inflammatory properties. In this study, we have investigated the effects of BR against cerulein-induced chronic pancreatitis (CP) via inhibition of TGF-β/Smad signaling and M2 macrophages polarization in AMPK dependent manner. Cerulein-induced CP mice were treated with BR (3 and 10 mg/kg), intraperitoneally every day for 21 days. Our results indicated that, BR treatment (10 mg/kg) significantly reduced oxidative-nitrosative stress, histological alterations, inflammatory cells infiltration and collagen deposition in pancreatic tissue. BR treatment also prevented cerulein-induced pancreatic stellate cells (PSCs) activation and extracellular matrix (ECM) deposition via downregulation of α-SMA, collagen1a, collagen3a and fibronectin expression. Mechanistically, treatment with BR significantly activated AMPK signaling as compared to cerulein-challenged mice. Further, administration of BR also inhibited TGF-β/Smad signaling and macrophages polarization in cerulein-induced CP in-vivo models and TGF-β1 stimulated RAW 264.7 macrophages in-vitro. Together, our results strongly suggest that BR treatment protected against cerulein-induced CP and associated fibrosis progression by inhibiting TGF-β1/Smad signaling and M2 macrophages polarization in an AMPK dependent manner.Copyright © 2020 Elsevier Inc. All rights reserved.

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