Inhibition of Snake Venom Enzymes and Antivenom Adjuvant Effects of Azadirachta indica A. Juss. (Meliaceae) Leaf Extracts

Abstract

Snake venom enzymes are the key substances involved in snake venom toxicity. Thus, inactivating these enzymes is generally considered to be the fundamental step in the management of snakebite. Conventionally, snakebite envenomation is treated parenterally with serum-based antivenins, and adjuvants to these antivenins are required for maximum protection of victims. Hence, this research was aimed at evaluating the inhibitory effect of Azadirachta indica leaf extracts on Naja nigricollis Reinhardt venom enzymes and screens for their antivenom adjuvant effects. A. indica leaf was collected, authenticated and extracted using 95% methanol followed by fractionation using hexane and ethyl acetate. The venom enzymes inhibition assays was evaluated using in vitro methods, while, adjuvant effect was screened using Albino rats. The results revealed that both the hexane and the ethyl acetate fractions showed capability of inhibiting the venom enzymes significantly (P<0.05) when compared with the venom controls in varying degrees of efficacies. For the adjuvant effect, no significant effect (P>0.05) of the venom at the administered dose was observed on bleeding time, clotting time, defibrinogenating and haemorrhagic effects compared to the normal control. However, the size of necrotic lesion and the percentage haemolysis were significantly (P<0.05) higher in the venom control rats. Both the hexane and the ethyl acetate fractions significantly mitigated these effects in the treated animals. The degree of protection was about 3 folds more than when the antivenin was used alone. Finally, these findings would be of importance in the area of drug development with a view to actualizing the substitution or enhancing the effect of conventional snakebite therapeutic options.

Antioxidant Enhancing Effect of Azadirachta indica A. Juss. Leaf Fractionated Extracts on Naja nigricollis Reinhardt Venom in Albino Rats

“…Tannins are water soluble phenolic substances with the ability to form complexes with proteins. Among its various biological activities are enzyme inhibition, inhibition of lipid peroxidation, scavenger of free radicals and anti-tumor action [51,52].…”

A Contemporary Exploration of Traditional Indian Snake Envenomation Therapies

“…Isolated organic fractions of methanolic leaf extract of Azadirachta indica significantly inhibited Naja nigricollis venom enzymes in vitro. A. indica extract acts as an effective adjuvant when used with snake venom antiserum in the treatment [169]. Aqueous and methanolic extracts of Azadirachta indica leaves are protective against Naja haje arabica and Bitis arietans arietans snake venoms in mice [170].…”

“…Various references demonstrate its effectiveness as an antidote for snake venom. Azadirachta indica [17,64,69,74,151,[164][165][166][167][168][169][170][171][172][173] and Rauvolfia serpentina [17,18,69,[87][88][89][90][91][92][93][94][95][96] hold second place in pharmacological evidence. Figure 3 depicts the number of appearances in references for each plant species as a snake venom antidote (labels as mentioned in the earlier section).…”

Prospects and Challenges of Developing Plant‐Derived Snake Antivenin Natural Products: A Focus on West Africa

“…Local effects induced by N. nigricollis’ venom such as necrotic lesion and hemolysis were significantly reduced in the group receiving ASV and the plant extract ( versus those receiving only ASV). The combination regimen afforded up to a 3‐fold improvement in venom‐protecting activity over ASV‐only treatment [131] . Abubakar et al.…”