Berberine attenuates severity of chronic pancreatitis and fibrosis via AMPK-mediated inhibition of TGF-ß1/Smad signaling and M2 polarization.
Toxicol Appl Pharmacol
; 403: 115162, 2020 09 15.
Article
em En
| MEDLINE
| ID: mdl-32721432
ABSTRACT
Berberine (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-ß/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-ß/Smad signaling and macrophages polarization in cerulein-induced CP in-vivo models and TGF-ß1 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-ß1/Smad signaling and M2 macrophages polarization in an AMPK dependent manner.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
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Berberina
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Fibrose
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Pancreatite Crônica
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Proteínas Smad
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article