allic Acid as a Non-Selective Inhibitor of alpha/beta-Hydrolase Fold Enzymes Involved in the Inflammatory Process: The Two Sides of the Same Coi

Autor(es)

Toyama, Marcos Hikari ^[1] ; Rogero, Airam ^[1] ; de Moraes, Laila Lucyane Ferreira ^[1] ; Fernandes, Gustavo Antonio ^[1] ; da Cruz Costa, Caroline Ramos ^{[1, 2]} ; Belchor, Mariana Novo ^{[1, 2]} ; De Carli, Agatha Manzi ^[1] ; de Oliveira, Marcos Antonio ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Biosci Inst, BIOMOLPEP Grp, BR-11330900 Sao Vicente, SP - Brazil

^[2] Fed Univ ABC, Postgrad Program Biotechnosci, BR-09210580 Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: HARMACEUTIC; v. 14, n. 2 FEB 2022.
• Citações Web of Science: 0

Resumo

(1) Background: Gallic acid (GA) has been characterized as an effective anti-inflammatory, antivenom, and promising drug for therapeutic use. (2/3) Methods and Results: GA was identified from ethanolic extract of fresh pitanga (Eugenia uniflora) leaves, which was identified using commercial GA. Commercial GA neutralized the enzymatic activity of secretory PLA2 (sPLA2) by inhibiting the active site and inducing changes in the secondary structure of the enzyme. Pharmacological edema assays showed that GA strongly decreased edema when the compound was previously incubated with sPLA2. However, prior treatment of GA (30 min before) significantly increased the edema and myotoxicity induced by sPLA2. The molecular docking results of GA with platelet-acetylhydrolase (PAF-AH) and acetylcholinesterase reveal that this compound was able to interact with the active site of both molecules, inhibiting the hydrolysis of platelet-activating factor (PAF) and acetylcholine (ACh). (4) Conclusion: GA has a great potential application; however, our results show that this compound can also induce adverse effects in previously treated animals. Additionally, the increased edema and myotoxicity observed experimentally in GA-treated animals may be due to the inhibition of PAF-AH and Acetylcholinesterase. (AU)

• Processo FAPESP: 20/03297-8 - Triagem e bioprospecção de compostos anti-inflamatórios em plantas Phyllanthus niruri, Eugenia uniflora, Schinus terebinthifolius e Jatropha gossypiifolia bioguiados por bioafinidade sobre a sPLA2 de Crotalus durissus terrificus
• Beneficiário: Gustavo Antonio Fernandes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 17/19942-7 - Busca de inibidores do sistema peroxirredoxina de patógenos e humanos
• Beneficiário: Marcos Antonio de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/20291-0 - Caracterização da atividade pró-inflamatória de uma nova serino protease (cdtsp-2) purificada do veneno total de Crotalus durissus terrificus
• Beneficiário: Marcos Hikari Toyama
• Modalidade de apoio: Auxílio à Pesquisa - Regular