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Myricetin ameliorates the severity of pancreatitis in mice by regulating cathepsin B activity and inflammatory cytokine production.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 Jul 30; Vol. 136, pp. 112284. Date of Electronic Publication: 2024 May 31. - Publication Year :
- 2024
-
Abstract
- Cathepsin B (CTSB) and inflammatory cytokines are critical in initiating and developing pancreatitis. Calcineurin, a central calcium (Ca <superscript>2+</superscript> )-responsive signaling molecule, mediates acinar cell death and inflammatory responses leading to pancreatitis. However, the detailed mechanisms for regulating CTSB activity and inflammatory cytokine production are unknown. Myricetin (MC) exhibits various biological activities, including anti-inflammatory effects. Here, we aimed to investigate MC effects on pancreatitis and the underlying mechanisms. Prophylactic and therapeutic MC treatment ameliorated the severity of cerulein-, L-arginine-, and PDL-induced acute pancreatitis (AP). The inhibition of CTSB activity by MC was mediated via decreased calcineurin activity and macrophage infiltration, not neutrophils infiltration, into the pancreas. Additionally, calcineurin activity inhibition by MC prevented the phosphorylation of Ca <superscript>2+</superscript> /CaM-dependent protein kinase kinase 2 (CaMKK2) during AP, resulting in the inhibition of CaMKIV phosphorylation and adenosine monophosphate-activated protein kinase (AMPK) dephosphorylation. Furthermore, MC reduced nuclear factor-κB activation by modulating the calcineurin-CaMKIV-IKKα/β-Iκ-Bα and calcineurin-AMPK-sirtuin1 axes, resulting in reduced production of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Our results showed that MC alleviated AP severity by inhibiting acinar cell death and inflammatory responses, suggesting that MC as a calcineurin and CaMKK2 signaling modulator may be a potential treatment for AP.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Male
Anti-Inflammatory Agents therapeutic use
Anti-Inflammatory Agents pharmacology
Calcium-Calmodulin-Dependent Protein Kinase Kinase metabolism
Ceruletide
NF-kappa B metabolism
Pancreas pathology
Pancreas drug effects
Pancreas immunology
Signal Transduction drug effects
Arginine metabolism
Disease Models, Animal
AMP-Activated Protein Kinases metabolism
Pancreatitis drug therapy
Pancreatitis immunology
Pancreatitis pathology
Pancreatitis chemically induced
Flavonoids pharmacology
Flavonoids therapeutic use
Cytokines metabolism
Cathepsin B metabolism
Mice, Inbred C57BL
Calcineurin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 136
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38823179
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112284