title: Guggulsterone attenuates cerulein-induced acute pancreatitis via inhibition of ERK and JNK activation.
abstract: Guggulsterone (GS), a plant steroid and a compound found at high levels in Commiphora myrrha, exhibits anti-inflammatory, anti-cancer, and cholesterol-lowering effects. However, the potential of GS to ameliorate acute pancreatitis (AP) is unknown. The aim of this study was to evaluate the effects of GS on cerulein-induced AP. AP was induced by intraperitoneally injecting supramaximal concentrations of the stable cholecystokinin analog cerulein (50 μg/kg) hourly for 6 h. In the GS-treated group, GS was administered intraperitoneally (10, 25, or 50mg/kg) 1 h before the first cerulein injection. Mice were sacrificed 6 h after the final cerulein injection. Blood samples were collected to measure serum lipase levels and evaluate cytokine production. The pancreas and lung were rapidly removed for morphologic and histological examinations, flow cytometry analysis, myeloperoxidase (MPO) assay, and real-time reverse transcription-polymerase chain reaction analysis. Pre-treatment with GS attenuated cerulein-induced histological damage, reduced pancreas weight/body weight ratio, decreased serum lipase levels, inhibited infiltrations of macrophages and neutrophils, and suppressed cytokine production. Additionally, GS treatment suppressed the activation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) in the pancreas in cerulein-induced pancreatitis. In conclusion, our results suggest that GS attenuates AP via deactivation of ERK and JNK.
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Dong-Goo
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Hanbang Body Fluid Research Center, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Gi-Sang
authors.initials: GS
authors.lastname: Bae
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Sun-Bok
authors.initials: SB
authors.lastname: Choi
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Il-Joo
authors.initials: IJ
authors.lastname: Jo
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Joon-Yeon
authors.initials: JY
authors.lastname: Shin
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Sung-Kon
authors.initials: SK
authors.lastname: Lee
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Myoung-Jin
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea.
authors.forename: Min-Jun
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Korean Medicine, Dongshin University, Naju, Jeonnam 520-714, South Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Jeong
authors.affiliation: Department of Obstetrics and Gynecology, College of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Choi
authors.affiliation: Department of Cosmetology, Dongshin University, Naju, Jeonnam 520-714, South Korea.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Seo
authors.affiliation: Department of Forest Resources, Gyeongnam National University of Science and Technology, Jinju, Gyeongnam 660-758, South Korea.
authors.forename: Gab-Chul
authors.initials: GC
authors.lastname: Choo
authors.affiliation: Department of Oriental Medicine Industry, Honam University, Gwangju 506-714, South Korea.
authors.forename: Sang-Wan
authors.initials: SW
authors.lastname: Seo
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 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, Iksan, Jeonbuk 540-749, South Korea; Department of Herbology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea; Hanbang Body Fluid Research Center, Wonkwang University, Iksan, Jeonbuk 540-749, South Korea. Electronic address: parksj08@wku.ac.kr.
authors.forename: Sung-Joo
authors.initials: SJ
authors.lastname: Park
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D002108:Ceruletide / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D005260:Female; D007274:Injections, Intraperitoneal; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008049:Lipase / Q000097:blood; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D011282:Pregnenediones / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; D002108:Ceruletide; C023617:pregna-4,17-diene-3,16-dione; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D008049:Lipase
keywords: (E)-Guggulsterone (GS); Acute pancreatitis (AP); Cytokine; Macrophage; Mitogen activated protein kinase (MAPK); Neutrophil