PDF(Pubmed)
Abstract：
Different species belonging to the genus Nephthea (Acyonaceae) are a rich resource for bioactive secondary metabolites. The literature reveals that the gastroprotective effects of marine secondary metabolites have not been comprehensively studied in vivo. Hence, the present investigation aimed to examine and determine the anti-ulcer activity of 4α,24-dimethyl-5α-cholest-8β,18-dihydroxy,22E-en-3β-ol (ST-1) isolated from samples of a Nephthea species. This in vivo study was supported by in silico molecular docking and protein-protein interaction techniques. Oral administration of ST-1 reduced rat stomach ulcers with a concurrent increase in gastric mucosa. Molecular docking calculations against the H+/K+-ATPase transporter showed a higher binding affinity of ST-1, with a docking score value of -9.9 kcal/mol and a pKi value of 59.7 nM, compared to ranitidine (a commercial proton pump inhibitor, which gave values of -6.2 kcal/mol and 27.9 µM, respectively). The combined PEA-reactome analysis results revealed promising evidence of ST-1 potency as an anti-ulcer compound through significant modulation of the gene set controlling the PI3K signaling pathway, which subsequently plays a crucial role in signaling regarding epithelialization and tissue regeneration, tissue repairing and tissue remodeling. These results indicate a probable protective role for ST-1 against ethanol-induced gastric ulcers.
摘要：
属于Nephthea属（Acyonaceae）的不同物种是生物活性次级代谢产物的丰富资源。文献表明，尚未在体内全面研究海洋次生代谢产物的胃保护作用。因此，本研究旨在检查和确定4α的抗溃疡活性，24-二甲基-5α-胆-8β，18-二羟基,22E-en-3β-ol(ST-1)分离自Nephthea物种的样品。这项体内研究得到了计算机分子对接和蛋白质-蛋白质相互作用技术的支持。口服ST-1可减少大鼠胃溃疡，同时增加胃粘膜。针对H+/K+-ATP酶转运蛋白的分子对接计算显示ST-1的结合亲和力更高，对接评分值为-9.9kcal/mol，pKi值为59.7nM，与雷尼替丁（一种商业质子泵抑制剂，给出的值为-6.2kcal/mol和27.9µM，分别)。联合PEA-反应组分析结果揭示了ST-1作为抗溃疡化合物通过显著调节控制PI3K信号通路的基因集的有希望的证据。随后在上皮形成和组织再生的信号传导中起着至关重要的作用，组织修复和组织重塑。这些结果表明ST-1可能对乙醇诱导的胃溃疡具有保护作用。
