Gastroprotection against Rat Ulcers by Nephthea Sterol Derivative

Biomolecules

Mahmoud A. A. Ibrahim¹  Mahmoud F. Moustafa²  Shifaa O. Alshammari³  Ahmed M. Al-Abd⁴  Mohamed A. M. Atia⁵  Tarik A. Mohamed⁶  Mohamed-Elamir F. Hegazy⁶  Sherin K. Ali⁶  Rania F. Ahmed⁷  Abdelsamed I. Elshamy⁷  Karam A. Mahdy⁸  Abdel Razik H. Farrag⁹ 

[1] Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt;Department of Biology, College of Science, King Khalid University, Abha 9004, Saudi Arabia;Department of Biology, College of Science, University of Hafr Al Batin, Hafar Al Batin 39524, Saudi Arabia;Department of Pharmaceutical Sciences, College of Pharmacy & Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman 4184, United Arab Emirates;Molecular Genetics and Genome Mapping Laboratory, Genome Mapping Department, Agricultural Genetic Engineering Research Institute (AGERI), Agricultural Research Center (ARC), Giza 12619, Egypt;National Research Centre, Chemistry of Medicinal Plants Department, 33 El−Bohouth St., Dokki, Giza 12622, Egypt;National Research Centre, Chemistry of Natural Compounds Department, Dokki, Giza 12622, Egypt;National Research Centre, Medical Biochemistry Department, 33 El Bohouth St., Dokki, Giza 12622, Egypt;National Research Centre, Pathology Department, 33 El Bohouth St., Dokki, Giza 12622, Egypt;

关键词: Nephthea species;    soft corals;    anti-ulcer activity;    molecular docking;    reactome analysis;   

DOI  :  10.3390/biom11081247

来源: DOAJ

【 摘 要 】

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 pK_i 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.

【 授权许可】

Unknown