Molecular docking analysis of major active compounds of pomegranate peel extract (Punica granatum L.) in inhibiting cyclooxygenase enzyme

Abstract

Background: Inflammation is the body's physiological response to an injury. Injury that affected the body can be a chemical agent, physical, or biological agent. Nowadays the inflammatory condition treated by eliminating the main etiological factor then prescribing anti-inflammatory drugs such as NSAIDs, but according the data in 2021 shown that 78,8% patients has gastritis side effect. Pomegranate peel extract (PPE) has good anti-inflammatory ability because it containing the highest concentration of flavonoid. Objectives: To predict the molecular inhibition of major active compounds (epigallocatachin gallate, ferulic acid, chlorogenic acid, gallic acid, caffeic acid, cianidanol, epicatechin, and punicalagin) in PPE against cyclooxygenase enzyme (COX-1 & COX-2) using in silico study. Method: Preparation of the active compounds of PPE, prediction of their activity, ADMET predicting test, physicochemical test, and molecular docking simulation. Results and discussions: In silico test showed that all common active compound of PPE that have potential as anti-inflammatory drugs. All of MAC PPE had value of Pa > 0.5. ADMET prediction showed that all common active compounds can distribute systemically because had score of log mucosal permeability < 2.5. All of common active compound in PPE had negative prediction not to toxic or triggering dermatitis contact against oral mucosa through ADMET prediction. The result of molecular docking of chlorogenic acid and punicalagin against protein of COX-2 showed ∆Gbind value more than mefenamic acid and arachidonic acid against COX-1 and COX-2 in range of -3,0 to -9,1 kcal/mol which the most effective as an anti-inflammatory is punicalagin (-4,0 & -9,1 kcal/mol). Conclusion: PPE had potential as anti-inflammatory drugs through COX-1 & COX-2 inhibition with the best anti-inflammation ability is ferrulic acid and punicalagin.