Inhibition of phospholipase A2 from Naja haje and Naja nigricollis venoms by active fraction of Moringa oleifera leaves: in vitro and in silico methods
A. Adeyi, Abideen Omobayo Jimoh, B. S. Ajisebiola, O. Adeyi, D. Metibemu, R. Okonji
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引用次数: 0
Abstract
Abstract Phospholipases are one of the principal toxic enzymes in snake venoms inducing a wide variety of pharmacological effects after envenomation. Natural inhibitors from plants are known to inhibit the toxic enzyme activities of snake venoms. In this study, ethanol crude extract of M. oleifera leaves was partitioned using n-hexane and ethyl acetate after which fractionation was done using column and thin layer chromatography. Subsequently, the inhibitory activities of the crude extract and sub-fractions of M. oleifera were investigated against phospholipases A2 isolated from Naja haje and Naja nigricollis venoms using in vitro and in-silico approaches while EchiTab-PLUS polyvalent antivenom was used as the standard drug. The molecular weight of isolated N. haje phospholipase A2 (NH-PL) and N. nigricollis phospholipase A2 (NN-PL) were 24.11 and 35.22 kDa respectively. NH-PL enzyme had a specific activity of 2.70 μM/min/mg substrate while NN-PL activity was 2.10 μM/min/mg substrate. The Km of NH-PL was 0.330 μM with Vmax of 0.085 μM/mL min while NN-PL had Vmax of 0.198 μM/mL.min and Km of 0.670 μM. M. oleifera n-hexane sub-fraction 5 (MOLH5) exhibited a total inhibition of NN-PL and NH-PL enzyme activities at all concentrations used. Molecular docking of the phytoconstituents of MOLH5 against the catalytic site of phospholipase A2 revealed 2-Hydrazino-8-hydroxy-4-phenylquinoline as the lead compound and a potential drug candidate with a docking score of −6.789 kcal/mol. Findings indicated that MOLH5 possesses phospholipase A2 natural inhibitors that could be explored as a therapy for snake envenoming.
期刊介绍:
Toxin Reviews provides an international forum for publishing state-of-the-art reviews and guest-edited single topic special issues covering the multidisciplinary research in the area of toxins derived from animals, plants and microorganisms. Our aim is to publish reviews that are of broad interest and importance to the toxinology as well as other life science communities. Toxin Reviews aims to encourage scientists to highlight the contribution of toxins as research tools in deciphering molecular and cellular mechanisms, and as prototypes of therapeutic agents. Reviews should emphasize the role of toxins in enhancing our fundamental understanding of life sciences, protein chemistry, structural biology, pharmacology, clinical toxinology and evolution. Prominence will be given to reviews that propose new ideas or approaches and further the knowledge of toxinology.