Diosmetin ameliorates the severity of cerulein-induced acute pancreatitis in mice by inhibiting the activation of the nuclear factor-κB.

Abstract

Diosmetin (3', 5, 7-trihydroxy-4'-methoxyflavone), the aglycone part of the flavonoid glycosides diosmin occurs naturally in citrus fruit, was considered to exhibit anti-inflammatory and antioxidant properties. Our study aimed to investigate the effect of diosmetin in a murine model of cerulein-induced acute pancreatitis (AP). Experimental AP was induced in mice by seven intraperitoneal injection of cerulein (50 ug/kg) at hourly intervals. Diosmetin (100 mg/kg) or vehicle was pretreated 2 h before the first cerulein injection. After 6 h, 9 h, 12 h of the first cerulein injection, the severity of acute pancreatitis was evaluated biochemically and morphologically. Pretreatment with diosmetin significantly reduced serum levels of amylase and lipase; the histological injury; the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6; myeloperoxidase (MPO) activity, trypsinogen activation peptide (TAP) level, the expression of inducible nitric oxide synthase (iNOS); and the nuclear factor (NF)-κB activation in cerulein-induced AP. This study showed that administration of diosmetin demonstrated a beneficial effect on the course of cerulein-induced AP in mice. Therefore, diosmetin may become a new therapeutic agent in future clinical trials for treatment of AP.

• Authors: Ge Yu, Rong Wan, Guojian Yin, Jie Xiong, Yanling Hu, Miao Xing, Xiaofeng Cang, Yuting Fan, Wenqin Xiao, Lei Qiu, Xingpeng Wang, Guoyong Hu
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 7 Issue 5 Pg. 2133-42 ( 2014) ISSN: 1936-2625 [Electronic] United States
• PMID: 24966921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Flavonoids
• Inflammation Mediators
• NF-kappa B
• Ceruletide
• diosmetin

Topics

• Active Transport, Cell Nucleus (drug effects)
• Acute Disease
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Ceruletide
• Cytoprotection
• Disease Models, Animal
• Flavonoids (pharmacology)
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Male
• Mice, Inbred C57BL
• NF-kappa B (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Pancreas (drug effects, metabolism, pathology)
• Pancreatitis (chemically induced, metabolism, pathology, prevention & control)
• Severity of Illness Index
• Signal Transduction (drug effects)
• Time Factors