Russelioside B; A pregnane glycoside for treatment of gastric ulcer via modulation of heat shock protein-70 and vascular endothelial growth factor
Russelioside B; A pregnane glycoside for treatment of gastric ulcer via modulation of heat shock protein-70 and vascular endothelial growth factor
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DOI：
10.1016/j.steroids.2020.108759
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发表时间：
2021-01-01
期刊：
影响因子：
2.7
通讯作者：
Abdel-Sattar, Essam A.
中科院分区：
文献类型：
--
作者：
El-Shiekh, Riham A.;Salama, Abeer;Abdel-Sattar, Essam A.
胃溃疡是一种非常常见的公共卫生问题，影响全球高达10%。Russelioside B是一种从几种水牛角属植物中分离得到的甾体糖苷。没有研究测试该化合物的溃疡愈合潜力。本研究旨在评估Russelioside B对乙醇诱导的大鼠胃粘膜损伤的保护作用。采用单次灌胃无水乙醇（5 mL/kg）诱发大鼠溃疡。将大鼠随机分为4组（n = 8），并在溃疡诱导前1 h经口灌胃给予治疗（Antodine，20 mg/kg或Russelioside B，50 mg/kg）。预先给予Russelioside B（50 mg/kg）可减轻胃粘膜损伤，表现为溃疡指数和组织学评分降低。它通过显著降低肿瘤坏死因子-α和白细胞介素-6水平以及髓过氧化物酶活性（这也是Covid-19感染的加重因素）来抑制胃部炎症。此外，给药罗素苷B通过维持还原型谷胱甘肽和减少丙二醛抑制脂质过氧化物来停止胃氧化应激。它还能够恢复由乙醇诱导的热休克蛋白-70、血管内皮生长因子和前列腺素E2水平的急剧下降。此外，它还表现出碳酸酐酶抑制活性。Russelioside B的胃保护作用通过多种机制作用来确定;抑制胃氧化应激、炎症、抗凋亡活性，并通过上调内皮生长因子、使热休克蛋白-70和前列腺素E2正常化来增强胃粘膜保护。这些作用在一定程度上与一些经典的抗溃疡药物（如安妥定）相当。
Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n = 8) and given treatments (Antodine, 20 mg/kg or russelioside B, 50 mg/kg) by oral gavage 1 h before ulcer induction. Pretreatment with russelioside B (50 mg/kg) attenuated the gastric mucosal injury as proved by a decrease of ulcer index, and histological scores. It suppressed the gastric inflammation by a significant lowering the tumor necrosis factor-alpha and interleukin-6 levels with myeloperoxidase activity (which are also aggravating factors in the case of Covid-19 infection). In addition, administration of russelioside B halted the gastric oxidative stress via inhibition of lipid peroxides by maintaining reduced glutathione and by decreasing malondialdehyde. It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. Additionally, it showed carbonic anhydrase inhibition activity. The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2. These actions were comparable in part to some classical antiulcer drugs such as Antodine.