Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abasia, Cairo, Egypt.
Eur J Pharmacol. 2018 Jan 5;818:486-498. doi: 10.1016/j.ejphar.2017.11.008. Epub 2017 Nov 8.
Gastric ulcer is one of the major gastrointestinal disorders affecting people worldwide. Despite medical advances, management of gastric ulcer and its complications remains a challenge facing medicine nowadays. In addition, currently available medicines exhibit limited efficacy and several side effects. In the current study, the potential protective effects of chrysin -naturally occurring flavonoid - were tested against indomethacin-induced gastric ulcer model in rats. It was found that chrysin in both doses; 50 and 100mg/kg were effective in promoting mucus secretion and preventing the rise in ulcer and lesion indices, acid production and histologic changes induced by indomethacin. During investigation of the possible underlying mechanisms, chrysin significantly attenuated indomethacin-induced oxidative injury and inflammatory response. Also, chrysin activated peroxisome proliferator activated receptor-ɣ (PPAR-ɣ) leading to a phenotypic switch from pro-inflammatory M1 macrophages to the anti-inflammatory M2 macrophages that evidenced by the upregulated mRNA expression levels of PPAR-ɣ and M2 marker genes (Arg-1 and CD206) and down regulation of M1 marker genes (IL-6 and CCL3). Furthermore, chrysin promoted angiogenesis via increasing expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and cluster of differentiation-31 (CD31). Collectively, these findings indicate that chrysin possesses a potential protective effect against indomethacin-induced gastric ulcer.
胃溃疡是影响全球人群的主要胃肠道疾病之一。尽管医学取得了进步，但胃溃疡及其并发症的治疗仍然是当今医学面临的挑战。此外，目前可用的药物显示出有限的疗效和几种副作用。在当前的研究中，测试了白杨素——一种天然存在的类黄酮——对大鼠吲哚美辛诱导的胃溃疡模型的潜在保护作用。结果发现，白杨素在 50 和 100mg/kg 两种剂量下均能有效促进黏液分泌，并防止吲哚美辛引起的溃疡和病变指数、胃酸分泌和组织学变化的升高。在研究可能的潜在机制时，白杨素显著减轻了吲哚美辛引起的氧化损伤和炎症反应。此外，白杨素激活过氧化物酶体增殖物激活受体-γ（PPAR-γ），导致从促炎 M1 巨噬细胞向抗炎 M2 巨噬细胞的表型转换，这表现在 PPAR-γ 和 M2 标志物基因（Arg-1 和 CD206）的 mRNA 表达水平上调和 M1 标志物基因（IL-6 和 CCL3）的下调。此外，白杨素通过增加血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和分化簇-31（CD31）的表达促进血管生成。总之，这些发现表明白杨素有潜力预防吲哚美辛诱导的胃溃疡。
