School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
Chem Biol Interact. 2016 Apr 25;250:68-77. doi: 10.1016/j.cbi.2016.03.003. Epub 2016 Mar 10.
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.
本研究旨在评价木香烃内酯（Co）和去氢木香内酯（De）对乙醇诱导的小鼠胃溃疡的抗溃疡活性，并阐明相关作用的潜在机制。小鼠连续 7 天口服 Co（5 或 20mg/kg）、De（5 或 20mg/kg）和奥美拉唑（OME，20mg/kg）预处理，然后用无水乙醇（0.2mL/20g 体重）诱导溃疡。与乙醇溃疡小鼠相比，Co 处理具有显著的胃保护作用，显著降低溃疡指数（ULI）和组织病理学损伤。Co 的每日胃内给药表现出强大的抗炎活性，表现为核因子（NF）-κB、肿瘤坏死因子（TNF）-α、一氧化氮（NO）、诱导型一氧化氮合酶（iNOS）、环氧化酶（COX）-2 的抑制以及白细胞介素（IL）-10 的增加。此外，Co 预处理有效抑制了乙醇诱导的丙二醛（MDA）过度产生，增加了耗竭的超氧化物歧化酶（SOD），并通过上调增殖细胞核抗原（PCNA）表达促进胃黏膜上皮细胞增殖。同样，De 对乙醇诱导的溃疡具有保护作用，这依赖于抑制炎症细胞因子和 MDA 的产生，但与 IL-10、SOD 和 PCNA 的改善无关。总之，这些结果清楚地表明 Co 和 De 对乙醇诱导的胃溃疡具有抗溃疡作用；然而，由于 Co 比 De 具有更多的多途径调节作用，因此 Co 的胃保护活性优于 De。这些发现表明，Co 或 De 可能成为一种新的有用的天然胃保护工具，用于治疗胃溃疡，为倍半萜内酯的胃保护提供了科学依据。
