a School of Pharmacy , Xi'an Jiaotong University , Xi'an , PR China.
Immunopharmacol Immunotoxicol. 2017 Dec;39(6):354-363. doi: 10.1080/08923973.2017.1379088. Epub 2017 Sep 26.
Gastric ulcer is a common gastrointestinal disorder with increasing incidence and prevalence attributed to loss of balance between aggressive and protective factors. Nobiletin (NOB), a major component of polymethoxyflavones in citrus fruits, has a broad spectrum of health beneficial properties including anti-inflammatory and anti-tumor activities. Although NOB was originally shown to possess anti-inflammatory activity, its effects on gastric ulcer were rarely explored previously.
The aim of the present study was to investigate the anti-ulcerogenic activity of NOB on ethanol-induced gastric ulcer in mice and to elucidate the underlying mechanisms.
Seventy-two male Kunming mice administered with absolute ethanol (0.2 ml/animal) were pretreated with NOB (5, 10 or 20 mg/kg), cimetidine (100 mg/kg), or vehicles by intragastric administration in different experimental groups for three days, and animals were euthanized 3 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration.
The results showed that ethanol induced gastric injury, increased malondialdehyde (MDA) levels, decreased glutathione (GSH) content, superoxide dismutase (SOD) activity, and prostaglandin E (PGE) levels, increased pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression MAPK signaling pathway. Pretreatment with NOB significantly attenuated the gastric lesions as compared to the ethanol group.
These findings suggest that the gastroprotective activity is attribute to the improvement of antioxidant activities, the stimulation of PGE, and the reduction of pro-inflammatory cytokines through the MAPK pathway.
胃溃疡是一种常见的胃肠道疾病，其发病率和患病率呈上升趋势，这归因于侵袭性和保护性因素之间失去平衡。川陈皮素（NOB）是柑橘类水果中多甲氧基黄酮的主要成分，具有广泛的健康有益特性，包括抗炎和抗肿瘤活性。尽管最初显示 NOB 具有抗炎活性，但以前很少探讨其对胃溃疡的作用。
本研究旨在研究 NOB 对乙醇诱导的小鼠胃溃疡的抗溃疡活性，并阐明其潜在机制。
给予 72 只雄性昆明小鼠 0.2ml/只的绝对乙醇，用 NOB（5、10 或 20mg/kg）、西咪替丁（100mg/kg）或不同实验组的载体通过灌胃预处理 3 天，在乙醇摄入后 3 小时处死动物。考虑到大体和微观病变、免疫和生化参数。
结果表明，乙醇诱导胃损伤，增加丙二醛（MDA）水平，降低谷胱甘肽（GSH）含量、超氧化物歧化酶（SOD）活性和前列腺素 E（PGE）水平，增加促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平和髓过氧化物酶（MPO）活性，以及 MAPK 信号通路的表达。与乙醇组相比，NOB 预处理显著减轻了胃损伤。
这些发现表明，胃保护活性归因于抗氧化活性的提高、PGE 的刺激以及通过 MAPK 途径减少促炎细胞因子。
