Biotransformation of Resveratrol and Its Affinity for COX-2: An In Silico Analysis of Its Anti-Inflammatory Potential
DOI:
https://doi.org/10.29105/respyn24.3-885Keywords:
Resveratrol, Inflamación, Polifenoles, Microbiota gastrointestinal, Biología computacionalAbstract
Introduction: Chronic inflammation is implicated in the pathogenesis of various degenerative diseases and is closely associated with the overexpression of cyclooxygenase-2 (COX-2), a key enzyme in the inflammatory response. Resveratrol, a phenolic compound found in grapes, berries, and peanuts, has demonstrated anti-inflammatory properties, partly attributed to its interaction with COX-2. Objective: To evaluate, using in silico tools, the gut microbiota-mediated biotransformation of resveratrol and the potential anti-inflammatory effects of its metabolites on COX-2. Material and method: The BioTransformer platform was used to predict structural modifications of resveratrol induced by microbial enzymes. The resulting metabolites, stilbendiol and stilbenol, were analyzed for their pharmacokinetic properties and potential molecular targets using SwissADME and SwissTargetPrediction. Their binding affinity to COX-2 was subsequently evaluated through molecular docking with AutoDock. Results: Computational analyses indicated that bacterial dehydroxylases generate two resveratrol derivatives: 3,4’-dihydroxy-trans-stilbene and trans-4-hydroxystilbene. Both compounds were predicted to target COX-2 (probability ≥ 0.4) and displayed favorable pharmacokinetic properties (LogP ≥ 2). However, molecular docking suggested that stilbenol has a stronger binding affinity to the COX-2 active site (−7.09 kcal/mol). Conclusion: Gut microbiota may enhance the anti-inflammatory efficacy of resveratrol through its biotransformation into more active metabolites, such as trans-4-hydroxystilbene. To the best of our knowledge, this is the first study to identify stilbenol as a potential COX-2 inhibitor.
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Copyright (c) 2025 Alejandra Niño Sánchez, Alpha Berenice Medellín Guerrero, Elizabeth Solís Pérez, Manuel López-Cabanillas Lomelí, Luis Fernando Méndez López
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