Exploring the inhibitory potential of phytochemicals from Vernonia glaberrima leaves against snake venom toxins through computational simulation and experimental validation.

Autor: Yusuf AJ; Department of Pharmaceutical and Medicinal Chemistry, Usmanu Danfodiyo University, Sokoto, Nigeria. Electronic address: amina.yusuf@udusok.edu.ng., Bugaje AI; Department of Pharmaceutical and Medicinal Chemistry, Usmanu Danfodiyo University, Sokoto, Nigeria., Sadiq M; Department of Pharmaceutical and Medicinal Chemistry, Usmanu Danfodiyo University, Sokoto, Nigeria., Salihu M; Department of Pharmaceutical and Medicinal Chemistry, Usmanu Danfodiyo University, Sokoto, Nigeria., Adamu HW; Department of Biology, Shehu Shagari College of Education, Sokoto, Nigeria., Abdulrahman M; Department of Pharmaceutical and Medicinal Chemistry, Usmanu Danfodiyo University, Sokoto, Nigeria.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2024 Aug 28; Vol. 247, pp. 107838. Date of Electronic Publication: 2024 Jul 05.
DOI: 10.1016/j.toxicon.2024.107838
Abstrakt: Phospholipase A 2 (PLA 2 ) is an enzyme present in appreciable quantity in snake venoms which catalyze the hydrolysis of glycerophospholipids at sn-2 position and promote the release of lysophospholipids and fatty acids. 5-methylcoumarin-4-β-glucoside (5MC4BG) and lupeol were previously isolated from the leaves of V. glaberrima. The aim of this research was to evaluate effect of these compounds as potential inhibitors of snake venom toxins of Naja nigricollis using an in vitro and in silico studies. Antisnake venom studies was conducted using acidimetry while the molecular docking analysis against PLA 2 enzyme from N. nigricollis was performed using Auto Dock Vina and ADME-Tox analysis was evaluated using swissADME and ProTox-II online servers. The two compounds (5MC4BG and Lupeol) were able to inhibit the hydrolytic actions of PLA 2 enzyme with percentage inhibition ranging from 23.99 to 72.36 % and 21.97-24.82 % at 0.0625-1.00 mg/mL respectively while the standard ASV had 82.63 % at 1.00 mg/mL after 10 min incubation at 37 °C. Similar effects were observed after 30 min incubation, although there was significant increase in percentage inhibition of 5MC4BG and lupeol ranging from 66.51 to 83.73 % and 54.87-59.60 % at similar concentrations. Furthermore, the compounds were able to bind to the active site of PLA 2 enzyme with high affinity (-7.7 to -6.3 kcal/mol); the standard ligand, Varespladib had a docking score of -6.9 kcal/mol and they exhibited favorable drug-likeness and pharmacokinetic properties and according to toxicity predictions, the two compounds are toxic. In conclusion, the leaf of V. glaberrima contains phytoconstituents with antisnake activity and thus, validates the hypothesis that, the phytoconstituents of V. glaberrima leaves has antisnake venom activity against N. nigricollis venom and thus, should be studied further for the development as antisnake venom agents.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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