El-Demerdash Aya A, Menze Esther T, Esmat Ahmed, Tadros Mariane G, Elsherbiny Doaa A
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Badr University in Cairo (BUC), Cairo, 11829, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1411-1424. doi: 10.1007/s00210-021-02067-5. Epub 2021 Feb 27.
Peptic ulcer including gastric and duodenal ulcers is a common gastro-intestinal disorder worldwide, associated with a significant mortality due to bleeding and perforation. Numerous efforts are being exerted to look for natural drugs that lack the potential side effects but still keep beneficial effects for treatment and/or prevention of gastric ulcer. Pinocembrin (PINO) is a natural flavonoid retaining anti-microbial, anti-oxidant, and anti-inflammatory activities. The present study was conducted to investigate the protective and therapeutic effects of PINO against indomethacin (INDO)-induced gastric ulcer in rats and the possible underlying mechanisms. PINO (25 and 50 mg/kg) promoted mucus secretion, decreased ulcer index, and inhibited histopathological changes induced by INDO. Further investigation of possible mechanisms showed that PINO significantly attenuated INDO-induced oxidative and inflammatory responses in both doses when administrated before or after ulcer induction. PINO downregulated mRNA expression level of p38-mitogen-activated protein kinase (p38-MAPK) which subsequently inhibited NF-κB activation and inflammatory cytokine release including tumor necrosis factor-α (TNF-α) and interleukin-1beta (IL-1β). Additionally, PINO inhibited apoptotic activity which was confirmed by downregulation of caspase-3 transcription. The current results demonstrated the promising therapeutic activity of PINO against INDO-induced gastric ulcer due to-at least partly-its anti-oxidant, anti-inflammatory, and anti-apoptotic effects.
消化性溃疡包括胃溃疡和十二指肠溃疡，是一种全球常见的胃肠道疾病，因出血和穿孔导致显著的死亡率。人们正在付出诸多努力寻找天然药物，这些药物缺乏潜在副作用，但对胃溃疡的治疗和/或预防仍具有有益作用。松属素（PINO）是一种具有抗菌、抗氧化和抗炎活性的天然黄酮类化合物。本研究旨在探讨PINO对吲哚美辛（INDO）诱导的大鼠胃溃疡的保护和治疗作用以及可能的潜在机制。PINO（25和50毫克/千克）促进黏液分泌，降低溃疡指数，并抑制INDO诱导的组织病理学变化。对可能机制的进一步研究表明，无论在溃疡诱导前还是诱导后给药，PINO在两种剂量下均能显著减轻INDO诱导的氧化和炎症反应。PINO下调p38丝裂原活化蛋白激酶（p38-MAPK）的mRNA表达水平，随后抑制NF-κB活化以及包括肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）在内的炎性细胞因子释放。此外，PINO抑制凋亡活性，这通过caspase-3转录的下调得到证实。目前的结果表明，PINO对INDO诱导的胃溃疡具有有前景的治疗活性，至少部分归因于其抗氧化、抗炎和抗凋亡作用。
