Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
J Ethnopharmacol. 2024 Dec 5;335:118617. doi: 10.1016/j.jep.2024.118617. Epub 2024 Jul 23.
Eucalyptus genus has been used for a very long time in conventional treatment as an anti-ulcer remedy.
The study aimed to explore the gastroprotective potential of 7-O-methyl aromadendrin (7-OMA), and sakuranetin (SKN) in comparison with omeprazole. The study tackled the contribution of their anti-inflammatory, antioxidant, and antiapoptotic capabilities to their anti-gastric ulcer effects.
An ethanol-induced gastric ulcer model in rats was adopted and the consequences were confirmed by a molecular docking study.
The oral pretreatment of rats 1 h before ethanol using omeprazole (20 mg/kg) or 7-OMA (20 or 40 mg/kg) or SKN (20 or 40 mg/kg) exhibited gastroprotective and anti-inflammatory properties to different extents. These amendments witnessed as restorations in the stomach histological architecture in H and E-stained sections, mucus content in periodic acid-Schiff (PAS) stained sections with increased cellular proliferation, as demonstrated by increased immunohistochemical staining of PCNA, and increments in stomach COX-1 activity and eNOS. The highest dose of SKN showed the best corrections to reach 4.8, 1.8, and 2.1 folds increase in PAS, COX-1 and eNOS, respectively as compared to the untreated ethanol-induced gastric ulcer group; effects that were comparable to that of omeprazole. Moreover, reductions in COX-2 activity, and the protein expression of NF-κB, IL-6, TNF-α and NOx, in addition to the gene expression of inducible iNOS were also noted. Moreover, the antioxidant and antiapoptotic capabilities of omeprazole, 7-OMA, and SKN were perceived. SKN (40 mg/kg) succeeded to show the unsurpassed results to reach 293.6%, 237.1%, 274.7%, 248.2%, and 175.4% in total and reduced GSH, catalase, SOD, and Bcl2, respectively, as well as 50.0%, 46.8%, and 52.1 % in oxidized GSSG, TBARS and caspase-3, respectively. The gastroprotective potential of the tested compounds can be assigned to their anti-inflammatory, antioxidant and antiapoptotic properties.7-OMA and SKN were studied using molecular docking into the binding sites of the most significant inflammatory targets, including COX-2, TNF-α, iNOS, and NF-κB. Pharmacokinetic and physicochemical parameters in silico were appropriate.
The prophylactic use of 7-OMA and SKN could be considered as an add-on to recurrent gastric ulcers and might influence its therapeutic approaches.
桉树属植物在传统治疗中被长期用作抗溃疡药物。
本研究旨在探索 7-O-甲基莪术二酮（7-OMA）和樱花素（SKN）的胃保护潜力，并与奥美拉唑进行比较。本研究探讨了它们的抗炎、抗氧化和抗凋亡能力对其抗胃溃疡作用的贡献。
采用乙醇诱导的大鼠胃溃疡模型，并通过分子对接研究证实其结果。
奥美拉唑（20mg/kg）或 7-OMA（20 或 40mg/kg）或 SKN（20 或 40mg/kg）在乙醇前 1 小时对大鼠进行口服预处理，在不同程度上表现出胃保护和抗炎作用。这些改良措施在 H 和 E 染色切片中恢复了胃组织学结构，在过碘酸希夫（PAS）染色切片中增加了细胞增殖的黏液含量，如增殖细胞核抗原（PCNA）的免疫组织化学染色增加所示，并且胃 COX-1 活性和 eNOS 增加。SKN 的最高剂量显示出最佳的校正作用，与未经治疗的乙醇诱导的胃溃疡组相比，PAS、COX-1 和 eNOS 分别增加了 4.8、1.8 和 2.1 倍；效果可与奥美拉唑相媲美。此外，还观察到 COX-2 活性、核因子-κB（NF-κB）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和一氧化氮合酶（NOS）的蛋白表达以及诱导型 iNOS 的基因表达减少。此外，还观察到奥美拉唑、7-OMA 和 SKN 的抗氧化和抗凋亡能力。SKN（40mg/kg）成功地达到了 293.6%、237.1%、274.7%、248.2%和 175.4%的总还原型谷胱甘肽（GSH）、过氧化氢酶、超氧化物歧化酶（SOD）和 Bcl2 以及 50.0%、46.8%和 52.1%的氧化型谷胱甘肽二硫化物（GSSG）、丙二醛（TBARS）和半胱天冬酶-3（caspase-3）的最佳结果。测试化合物的胃保护潜力可归因于其抗炎、抗氧化和抗凋亡特性。使用分子对接研究了 7-OMA 和 SKN 进入最重要的炎症靶点，包括 COX-2、TNF-α、iNOS 和 NF-κB 的结合位点。计算机模拟的药代动力学和物理化学参数是合适的。
预防性使用 7-OMA 和 SKN 可考虑作为复发性胃溃疡的附加治疗方法，并可能影响其治疗方法。
