title: Berberine inhibits inflammatory mediators and attenuates acute pancreatitis through deactivation of JNK signaling pathways.
abstract: Acute pancreatitis (AP) is a life-threatening disease. Berberine (BBR), a well-known plant alkaloid, is reported to have anti-inflammatory activity in many diseases. However, the effects of BBR on AP have not been clearly elucidated. Therefore, the present study aimed to investigate the effects of BBR on cerulein-induced AP in mice. AP was induced by either cerulein or l-arginine. In the BBR treated group, BBR was administered intraperitoneally 1h before the first cerulein or l-arginine injection. Blood samples were obtained to determine serum amylase and lipase activities and nitric oxide production. The pancreas and lung were rapidly removed for examination of histologic changes, myeloperoxidase (MPO) activity, and real-time reverse transcription-polymerase chain reaction. Furthermore, the regulating mechanisms of BBR were evaluated. Treatment of mice with BBR reduced pancreatic injury and activities of amylase, lipase, and pancreatitis-associated lung injury, as well as inhibited several inflammatory parameters such as the expression of pro-inflammatory cytokines and inducible nitric oxide synthesis (iNOS). Furthermore, BBR administration significantly inhibited c-Jun N-terminal kinase (JNK) activation in the cerulein-induced AP. Deactivation of JNK resulted in amelioration of pancreatitis and the inhibition of inflammatory mediators. These results suggest that BBR exerts anti-inflammatory effects on AP via JNK deactivation on mild and severe acute pancreatitis model, and could be a beneficial target in the management of AP.
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea; Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea.
authors.forename: Sun-Bok
authors.initials: SB
authors.lastname: Choi
authors.affiliation: Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea; Hanbang Body Fluid Research Center, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea.
authors.forename: Gi-Sang
authors.initials: GS
authors.lastname: Bae
authors.affiliation: Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea; Hanbang Body Fluid Research Center, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea.
authors.forename: Il-Joo
authors.initials: IJ
authors.lastname: Jo
authors.affiliation: School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia 750004, China.
authors.forename: Shaofan
authors.initials: S
authors.lastname: Wang
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea; Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea.
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Song
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea; Department of Herbology, School of Korean Medicine, Wonkwang University, Jeonbuk Iksan 540-749, South Korea; Hanbang Body Fluid Research Center, Wonkwang University, Jeonbuk, Iksan 540-749, South Korea. Electronic address: parksj08@wku.ac.kr.
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019283:Pancreatitis, Acute Necrotizing / Q000473:pathology*
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D001599:Berberine
keywords: Acute pancreatitis; Berberine; Cytokine; JNK; iNOS