Vanillic acid as phospholipase A₂ and proteases inhibitor: In vitro and computational analyses

Abstract

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 (∼25% inhibition); the caseinolytic activity induced by Bothrops atrox (∼30%), Bothrops jararacussu (∼44%), and C. d. terrificus (∼33%); the fibrinogenolysis induced by B. jararacussu, B. atrox, and C. d. terrificus (100%); the serine protease activity induced by Bothrops moojeni (∼45%) and Bothrops jararaca (∼66%); the hemolytic activity induced by B. moojeni (∼26%); the thrombolysis activity induced by B. atrox (∼30%) and B. jararacussu (∼20%); and the thrombotic activity induced by C. d. terrificus (∼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.

Effects of Vanillic Acid on Dynamic Fermentation Parameter, Nitrogen Distribution, Bacterial Community, and Enzymatic Hydrolysis of Stylo Silage

“…Stylo silage without further treatments might bear a high risk of remarkable nutrient loss and extensive proteolysis in that a high moisture condition would favor clostridial fermentation and butyric acid generation (Borreani et al, 2018;He et al, 2019c). Accordingly, VA addition might help improve microbial fermentation and protein preservation during ensiling process due to its great antimicrobial activity and inhibitory effects on different classes of enzymes (Henrique Cesar et al, 2020;Yao et al, 2020).…”

“…It possesses a variety of pharmacologic activities such as inhibiting carcinogenesis, antioxidative, antihypertensive, antiinflammatory, and antimicrobial activity (Calixto-Campos et al, 2015;Qian et al, 2020;Salau et al, 2020). Moreover, such biological functions might be partly owed to its inhibitory effects on different classes of enzymes like cyclooxygenase-2, phospholipases, and proteases (Henrique Cesar et al, 2020). Recently, VA has been widely used as preservatives, a flavoring agent in foods, cosmetics, and drugs, or an antioxidant with beneficial activities (Yao et al, 2020).…”

Advances in the Therapeutic Application of Small-Molecule Inhibitors and Repurposed Drugs against Snakebite

“…Recently, an oxidized form of vanillin is a phenolic compound derived from hydroxycinnamic acid, referred to here as compound 8 (C 8 H 8 O 4 , Figure ), was investigated for its inhibitory potential against enzymes from Bothrops spp. and C. d. terrificus venoms . Compound 8 showed inhibition of the following enzyme and pharmacological activities: PLA 2 activity of the B. alternatus venom at 1:1 (venom: 8 , w:w) ratio with ∼25% inhibition; 1:5 (venom: 8 , w:w) ratio with ∼28.3% inhibition, and 1:10 (venom: 8 , w:w) ratio with ∼33.6% inhibition Caseinolytic (protease) activity at 1:0.6 (venom: 8 , w:w) ratio of the B. atrox (∼32% inhibition), B. jararacussu (∼39% inhibition), and C. d. terrificus venoms (∼32% inhibition) Fibrinogenolytic activity of the B. jararacussu and C. d. terrificus venoms (100% inhibition) at 1:1 (venom: 8 , w:w) ratio Serine protease activity of the B. moojeni (∼25% inhibition) and B. jararaca venoms (∼66% inhibition) at 1:1 (venom: 8 , w:w) ratio Hemolytic activity of the B. moojeni venom (∼30% inhibition) at 1:04, 1:0.08, and 1:0.16 (venom: 8 , w:w) ratios Thrombolysis activity of the B. atrox (∼30% inhibition) and B. jararacussu venoms (∼20% inhibition) at 1:1 (venom: 8 , w:w) ratio Feeble inhibition of the thrombotic activity of the C. d. terrificus venom (∼8% inhibition) at 1:1 (venom: 8 , w:w) ratio …”

Evaluation of Protection by Caffeic Acid, Chlorogenic Acid, Quercetin and Tannic Acid against the In Vitro Neurotoxicity and In Vivo Lethality of Crotalus durissus terrificus (South American Rattlesnake) Venom

“…Vanillic acid inhibited the PLA 2 activity of Bothrops alternatus (∼25% inhibition) and the caseinolytic activity of Bothrops atrox (∼30%), Bothrops jararacussu (∼44%), and C. d. terrificus (∼33%). [11] Antibodies against synthetic peptides Antigenicity/immunogenicity of crotoxin and crotamine.…”