Potencial modulador dos metabólitos da semente e polpa de Euterpe oleracea Mart. sobre a via Orai1/STIM1/NFAT de linfócitos T: uma abordagem in silico

Abstract

The species Euterpe oleracea Mart, known as açaí and native to the Amazon region, is valued for its nutritional properties and health benefits, including antioxidant, anti-inflammatory and immunomodulatory activities. However, the full potential action of the secondary metabolites of this plant species on the immune system is not yet known. In this context, the present work aimed at the in silico evaluation of major compounds from açaí seed extract and pulp in the Orai1/STIM1/NFAT pathway of T lymphocyte activation. The compounds procyanidin C1 (PCC1), Epigallocatechin-3,3-di-O-Gallate (EGCdiG), patulithrin (PAT) and cyanidin (CY) were selected for computational analysis. The structures of the compounds were obtained from PubChem and used to evaluate the physicochemical characteristics, prediction of biological activity spectra, toxicological data, theoretical oral bioavailability, interaction profile of compounds with pharmacological targets, and interaction with proteins of the pathway of interest through molecular docking. All compounds evaluated showed relevant physicochemical properties, showing promise for some route of administration in the radar bioavailability analysis, with emphasis on cyanidin and patulithrin with the best oral bioavailability. According to pharmacokinetic parameters, these two compounds showed potential for absorption in the gastrointestinal tract and penetration through the skin. PASS predictions of biological activity spectra revealed that all compounds have potential for various activities, including peroxidase inhibition, free radical scavenging, antioxidant effects, and regulation of the immunoinflammatory response. Furthermore, CY and PAT exhibited low toxic potential in hepatotoxicity, cytotoxicity and mutagenicity. Molecular docking analysis demonstrated that CY (-7.0 kcal/mol) and PAT (-8.3 kcal/mol) bind to the Orai1 regulatory site (Ala282 and Phe171, respectively), while EGCdiG (-7.0 kcal/mol) and CY (-6.0 kcal/mol) exhibited affinity for the STIM1 activation/regulation site (Gly22 and Asp32, respectively). These results demonstrate that the selected compounds, mainly cyanidin and patulithrin, present characteristics that validate their future use as modulating agents of T lymphocyte activity, due to their interaction with proteins of the Orai1/STIM1/NFAT pathway.