title: Evaluation of protective effects of costunolide and dehydrocostuslactone on ethanol-induced gastric ulcer in mice based on multi-pathway regulation.
abstract: The aim of the present study was to evaluate the anti-ulcerogenic activity of costunolide (Co) and dehydrocostuslactone (De) on ethanol-induced gastric ulcer in mice and to elucidate the potential mechanisms of the action involved. Mice were pretreated orally with Co (5 or 20 mg/kg), De (5 or 20 mg/kg) and omeprazole (OME, 20 mg/kg) for 7 consecutive days, followed by ulcer induction using absolute ethanol (0.2 mL/20 g body weight). Treatment with Co had a remarkable gastroprotection compared to the ethanol-ulcerated mice that significantly reduced the ulcerative lesion index (ULI) and histopathological damage. Daily intragastric administration of Co exerted a powerful anti-inflammatory activity as evidenced by the suppression of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, as well as increased interleukin (IL)-10. Also, pretreatment with Co effectively inhibited ethanol-induced malondialdehyde (MDA) overproduction, increased the depleted superoxide dismutase (SOD) and promoted gastric mucosa epithelial cell proliferation by up-regulating proliferating cell nuclear antigen (PCNA) expression. Similarly, De had a protective effect on ethanol-induced ulcer, which was dependent on the inhibition of inflammatory cytokines and MDA generation, but independent of IL-10, SOD and PCNA improvement. Conclusively, the results have clearly demonstrated the anti-ulcerogenic potential of Co and De on ethanol-induced gastric ulcer; nevertheless, the gastroprotective activity of Co was superior to De due to more multi-pathway regulation than De. These findings suggested that Co or De could be a new useful natural gastroprotective tool against gastric ulcer, which provided a scientific basis for the gastroprotection of sesquiterpene lactones.
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Special Drugs R & D Center of People's Armed Police Forces, Department of Pharmacy, Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors.forename: Jingze
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Tianjin Lerentang Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co., Ltd., Tianjin 300380, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tianjin Lerentang Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co., Ltd., Tianjin 300380, China.
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Hanhan
authors.initials: H
authors.lastname: Huang
authors.affiliation: College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Man
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address: pharmgao@tju.edu.cn.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Gao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D000431:Ethanol; D007783:Lactones / Q000627:therapeutic use*; D051379:Mice; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000032:analysis / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000975:Antioxidants; D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000431:Ethanol; C083030:dehydrocostus lactone; C002602:costunolide; D052247:Nitric Oxide Synthase Type II
keywords: Anti-inflammation; Antioxidant; Cell proliferation; Costunolide; Dehydrocostuslactone; Gastric ulcer