Vanillic Acid As Phospholipase A(2) And Proteases Inhibitor: In Vitro And Computational Analyses

Enzymatic inhibition by natural compounds may represent a valuable adjuvant in snakebite serum therapy. The objective in this work was to evaluate possible in vitro interactions between vanillic acid and enzymes from Bothrops spp. and Crotalus durissus terrificus venoms, and also suggest a theory as how they interact based on molecular docking. Vanillic acid inhibited the phospholipase activity induced by Bothrops alternatus (similar to 25% inhibition); the caseinolytic activity induced by Bothrops atrox (similar to 30%), Bothrops jararacussu (similar to 44%), and C. d. terrificus (similar to 33%); the fibrinogenolysis induced by B. jararacussu, B. atrox, and C. d. terrificus (100%); the serine protease activity induced by Bothrops moojeni (similar to 45%) and Bothrops jararaca (similar to 66%); the hemolytic activity induced by B. moojeni (similar to 26%); the thrombolysis activity induced by B. atrox (similar to 30%) and B. jararacussu (similar to 20%); and the thrombotic activity induced by C. d. terrificus (similar to 8%). The compound was also capable of delaying the coagulation time in citrated plasma by 60, 35, and 75 Sec, when incubated with B. moojeni, B. atrox, and B. jararaca, respectively. The results obtained expand the possibilities for future pharmaceutical use of vanillic acid, considering the high homology degree among human and snake venom phospholipases A(2) and proteases (involved in chronic inflammatory diseases). Also, this compound can be used as adjuvant to improve currently available treatments for ophidism victims.