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

Abstract

(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.

Mass Spectrometric Identification of Licania rigida Benth Leaf Extracts and Evaluation of Their Therapeutic Effects on Lipopolysaccharide-Induced Inflammatory Response

“…This anti-inflammatory effect may also be associated with the presence of gallic acid in both AELR and HELR extracts. It is noteworthy that our results with both L. rigida extracts are corroborated by other reports, indicating that gallic acid is a subject of study due to its beneficial therapeutic activities, such as its role in the regulation of extracellular platelet-activating factor and modulation of the inflammatory process [ 49 , 50 ].…”

Assessing the Potential of Gallic Acid and Methyl Gallate to Enhance the Efficacy of β-Lactam Antibiotics against Methicillin-Resistant Staphylococcus aureus by Targeting β-Lactamase: In Silico and In Vitro Studies

“…GA and MG, which are secondary metabolites of plants generally found in many foods and beverages, have gained attention due to their favorable safety information [11,12]. GA and MG have been reported to offer many health benefits, including antioxidant [13], anti-cancers [14,15], anti-inflammatory [16,17] and antimicrobial effects [18][19][20]. Their pharmacological activities have been documented to be associated with enzyme inhibition because of the protein-binding capabilities of phenolic compounds [21].…”

“…For example, Sharanya et al (2018) showed that MG could inhibit lipoxygenase activity through wetlaboratory experiments and in silico studies, highlighting its potential anti-inflammatory therapy [16]. Similarly, GA shows promise in inflammatory therapy due to its inhibitory effect on phospholipase A2 [17]. However, the inhibition of bacterial enzymes or virulence by other phenolic compounds have been reported to be either associated or not associated with their antibacterial activity [22].…”

Gallic Acid Substance Appraisal in Daucus Carota Sp. Sativus and Genus Vitis by Conventional Withdrawal and High Performance Liquid Chromatography

“…GA bio efficacy impact has been the subject of many research papers and reviews to date. GA has many biological properties 1 which includes antioxidant [2][3] , anticancer property [4][5] , anti-inflammatory 6 , antidiabetic [7][8] , anti-ulcerogenic 9 . GA is also safe against disorders like radical oxygen species (ROS), hyper production, oxidative stress (OS) 10 and bacterial infections 11 .…”