title: 2',4',6'-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury.
abstract: Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2',4',6'-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 by inhibiting NF-κB and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-α, IL-1β, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-κB/ERK1/2 reduced acinar cell death and production of TNF-α, IL-1β, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.
authors.affiliation: Dept. of Herbology, College of Oriental Medicine, Wonkwang Univ., Iksan, Jeonbuk, South Korea.
authors.forename: Tae-Hyeon
authors.initials: TH
authors.lastname: Kim
authors.forename: Gi-Sang
authors.initials: GS
authors.lastname: Bae
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Oh
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Kyoung-Chel
authors.initials: KC
authors.lastname: Park
authors.forename: Bon Soon
authors.initials: BS
authors.lastname: Koo
authors.forename: Byung-Jin
authors.initials: BJ
authors.lastname: Kim
authors.forename: Yun-Sik
authors.initials: YS
authors.lastname: Yang
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Park
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Sang-Wan
authors.initials: SW
authors.lastname: Seo
authors.forename: Yong Kook
authors.initials: YK
authors.lastname: Shin
authors.forename: Ki-Jung
authors.initials: KJ
authors.lastname: Yun
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Sohn
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Rae-Kil
authors.initials: RK
authors.lastname: Park
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Song
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Park
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002108:Ceruletide; D047188:Chalcones / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008049:Lipase / Q000097:blood; D055370:Lung Injury / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C510589:2',4',6'-tris(methoxymethoxy) chalcone; D000893:Anti-Inflammatory Agents; D047188:Chalcones; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases; D008049:Lipase; D000681:Amylases