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

Journal Article · Sat Sep 15 04:00:00 UTC 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.07.101· OSTI ID:23105538

Jia, Rongrong; Ma, Jiali; Meng, Wenying; Wang, Na ^[1]

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1. Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

Highlights: • Dihydromyricetin (DHM) inhibits caerulin-induced cytokine production in BMDMs. • DHM inhibits caerulin-induced TRAF3-MKK3-p38 cascade activation in BMDMs. • DHM attenuates the cytotoxicity of caerulin-activated BMDMs to pancreatic acinar cells. • DHM inhibits pancreatic and systemic inflammation in caerulin-induced AP mice. 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.

• OSTI ID: 23105538
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 503; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BONE MARROW
LYMPHOKINES
MACROPHAGES
MICE
PANCREAS
PHOSPHOTRANSFERASES