Gallic Acid as a Non-Selective Inhibitor of α/β-Hydrolase Fold Enzymes Involved in the Inflammatory Process: The Two Sides of the Same Coin

Pharmaceutics

Mariana Novo Belchor¹  Gustavo Antônio Fernandes¹  Caroline Ramos da Cruz Costa¹  Marcos Hikari Toyama¹  Laila Lucyane Ferreira de Moraes¹  Agatha Manzi De Carli¹  Airam Rogero¹  Marcos Antônio de Oliveira¹ 

[1] BIOMOLPEP Group, Biosciences Institute, São Paulo State University (UNESP), São Vicente 11330-900, São Paulo, Brazil;

关键词: gallic acid;    edema;    myotoxic effect;    snake venom;    phospholipase A2;   

DOI  :  10.3390/pharmaceutics14020368

来源: DOAJ

【 摘 要 】

(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.

【 授权许可】

Unknown