Dihydromyricetin inhibits caerulin-induced TRAF3-p38 signaling activation and acute pancreatitis response

Biochem Biophys Res Commun. 2018 Sep 10;503(3):1696-1702. doi: 10.1016/j.bbrc.2018.07.101. Epub 2018 Jul 26.


Acute pancreatitis (AP) is a common inflammatory disease in gastrointestinal tract. Our previous study has shown that caerulin induces TNF receptor-associated factor 3 (TRAF3)-p38 signaling activation and pro-inflammatory response in macrophages, causing damage to co-cultured pancreatic acinar cells. Dihydromyricetin (DHM) is a flavonoid extracted from Ampelopsis grossedentata, which has displayed anti-inflammation and anti-oxidant functions. Our results here show that DHM potently inhibited caerulin-induced expression and productions of multiple pro-inflammatory cytokines (IL-1β, TNF-α and IL-17) in murine bone marrow-derived macrophages (BMDMs). DHM significantly inhibited caerulin-induced TRAF3 protein stabilization, TRAF3-mitogen-activated protein kinase kinase 3 (MKK3) association and following MKK3-p38 activation in BMDMs. Significantly, DHM was ineffective against caerulin in TRAF3-silenced BMDMs. Importantly, DHM supplement attenuated the cytotoxicity of caerulin-activated BMDMs to co-cultured pancreatic acinar cells, resulting in significantly decreased acinar cell death and apoptosis. In vivo, DHM co-administration largely attenuated pancreatic and systemic inflammation in caerulin-injected AP mice. Together, DHM inhibits caerulin-induced TRAF3-p38 signaling activation and AP response. DHM could be further studied as a potential anti-AP agent.

Keywords: Acute pancreatitis; Caerulin; Dihydromyricetin; Pro-inflammatory response; TRAF3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Ceruletide / antagonists & inhibitors*
  • Ceruletide / pharmacology
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis
  • Flavonols / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Pancreatitis / drug therapy*
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Signal Transduction / drug effects*
  • TNF Receptor-Associated Factor 3 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Cytokines
  • Flavonols
  • TNF Receptor-Associated Factor 3
  • Ceruletide
  • p38 Mitogen-Activated Protein Kinases
  • dihydromyricetin