摘要
Objective:To evaluate the neutralizing effects of flavonoids on snake venom toxicity by stand-alone and combinatorial approaches.Methods:Synthetic flavonoids were assessed,either individually or in combination with antivenom,for their neutralization of phospholipase A_(2)(PLA_(2)),protease,antioxidant(DPPH)assay and hemotoxic activity.Molecular docking studies were performed to understand possible binding of flavonoids with Naja naja venom PLA_(2).In vivo studies were carried out to confirm the neutralisation effects using a mouse model.Moreover,inhibition of PLA_(2) was monitored using combinatorial approaches.Results:Among the flavonoids used,quercetin and naringenin inhibited PLA_(2)(56%and 45%),protease(71%and 64%),DPPH scavenging(69.0%and 77.5%)and hemotoxic(70%)activities.Molecular docking studies indicated that the flavonoids bind to the substrate-binding site of PLA_(2)(Cys44 and Tyr63).In vivo studies showed a reduction in the venom toxicity level in the presence of naringenin.Additionally,combinatorial studies using the mixture of flavonoid and anti-venom revealed the possibility of synergistic effect(up to 32%enhancement)in neutralising the venom enzymes.Conclusions:These flavonoids can be used as additives for the treatment of snake bites,which may exert synergistic effects in combination with antivenom and decrease the post-therapeutic effects caused by excessive use of antivenom.
