Mahmoud Mona F, Abdo Walied, Nabil Mohamed, Drissi Badreddine, El-Shazly Assem M, Abdelfattah Mohamed A O, Sobeh Mansour
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El Sheikh 33516, Egypt.
Biomed Pharmacother. 2023 Apr;160:114331. doi: 10.1016/j.biopha.2023.114331. Epub 2023 Feb 1.
Malus domestica Borkh, the apple tree, exhibited numerous pharmacological properties including antioxidant, neuroprotective, anti-inflammatory, anticancer and antimicrobial activities. The present work aimed to annotate the secondary metabolites from a butanol fraction of apple leaves (BLE), evaluate the gastro-protective and healing effects of this fraction against indomethacin-induced gastric ulcers in rats and to identify its mechanism of action. BLE (100, and 200 mg/kg) was orally administered in rats as an acute treatment against indomethacin-induced gastric ulcer in comparison with famotidine as reference anti-ulcer drug. The stomachs of rats were collected to determine the ulcer index, the preventive ratio, measure the activity of glutathione peroxidase (GPx), and estimate the expression of cyclooxygenase-2 (COX-2), and heat shock protein 70 (HSP70). Furthermore, we evaluated both inflammatory and oxidative stress markers in the gastric tissues. We also performed histopathological study of gastric mucosa using H&E stain and periodic Schiff base stain to evaluate both gastric injury scores and gastric mucus content respectively. Pretreatment with BLE markedly lowered the severity of gastric injury induced by indomethacin, decreased oxidative stress, inflammatory cytokines, and COX-2 expression in the examined gastric tissues. The gastric healing effect of BLE was associated with increased mucoglycoproteins, and HSP70 expression. Additionally, gastric healing effect of high dose of BLE was superior to that of famotidine in decreasing gastric injury scores, COX-2, inflammatory cytokines, lipid peroxidation and in increasing gastric mucin content, HSP70, and reduced glutathione. These findings indicate that BLE is effective in accelerating ulcer healing by boosting HSP70 expression, and decreasing COX-2 expression, oxidative stress, and gastric inflammation which might be related to the presence of 21 phytoconstituents.
苹果树（苹果，学名：Malus domestica Borkh）具有多种药理特性，包括抗氧化、神经保护、抗炎、抗癌和抗菌活性。本研究旨在对苹果叶丁醇提取物（BLE）中的次生代谢产物进行注释，评估该提取物对吲哚美辛诱导的大鼠胃溃疡的胃保护和愈合作用，并确定其作用机制。将BLE（100和200mg/kg）经口给予大鼠，作为对吲哚美辛诱导的胃溃疡的急性治疗，与法莫替丁作为参考抗溃疡药物进行比较。收集大鼠的胃以测定溃疡指数、预防率，测量谷胱甘肽过氧化物酶（GPx）的活性，并评估环氧合酶-2（COX-2）和热休克蛋白70（HSP70）的表达。此外，我们还评估了胃组织中的炎症和氧化应激标志物。我们还使用苏木精和伊红染色以及过碘酸希夫碱染色对胃黏膜进行组织病理学研究，分别评估胃损伤评分和胃黏液含量。用BLE预处理可显著降低吲哚美辛诱导的胃损伤严重程度，降低所检测胃组织中的氧化应激、炎性细胞因子和COX-2表达。BLE的胃愈合作用与黏糖蛋白增加和HSP70表达增加有关。此外，高剂量BLE在降低胃损伤评分、COX-2、炎性细胞因子、脂质过氧化以及增加胃黏液含量、HSP70和还原型谷胱甘肽方面的胃愈合作用优于法莫替丁。这些发现表明，BLE通过提高HSP70表达、降低COX-2表达、氧化应激和胃炎症来有效加速溃疡愈合，这可能与21种植物成分的存在有关。
