Abstract
Background and objectives: Sambucus ebulus (SE) fruits are applied in folk medicine for the treatment of inflammatory gastrointestinal disorders and for immune stimulation in the autumn–winter period. LS-MS analysis has revealed that 5-O-Caffeoylquinic acid (Compound 1, C1), Cyanidin-3-O-Galactoside chloride (Compound 2, C2) and L-Epicatechin (Compound 3, C3) are among the most abundant polyphenolic compounds in SE fruit extracts. The aim of the present study was to perform in silico 3D/4D QSAR prediction of their anti-inflammatory properties, metabolism, and cytotoxicity. Methods: Prediction was performed using molecular exterior- and molecular interior-based 3D/4D QSAR analysis with CiS/MC and AlteQ platforms. Calculated probability ranged from 0 (no probability) to 1 (high probability). Results: Anti-inflammatory testing predicted a very high probability to reduce carrageenan-induced paw edema in rats (0.96, 50–60% inhibition of inflammation) for C3; intermediate COX2 inhibition for C2 (0.770, 11–19% inhibition), C1, (0.682, 7–10% inhibition) and C3 (0.500, 2–7% inhibition); low inhibition of COX1 for C2 (0.370), C3 (0.355), and C1 (0.206); low inhibition of LOX-5 for C2 (0.376) and low anti-peritoneal activity for C2 (0.345), C1 (0.339), and C3 (0.307). Cytotoxicity testing predicted low activity for C2 (0.122) and C3 (0.271), and C1 (0.305). Metabolism modelling revealed high probability of the biotransformation of C1 (0.904, 4 metabolites) and C3 (0.817, 3 metabolites) and low probability of the biotransformation of C2 (0.347) by CYP3A4. It also revealed high probability of biotransformation of C2 (0.869, 4 metabolites) and low probability of C3 (0.500) by CYP2D6. Discussion: 3D/4D QSAR in silico modelling appears to be a fast method for screening the possible biological properties of polyphenolic compounds. The method could be of interest in screening for new biologically active compounds for application in different industries, including in nutrition, pharmaceuticals, cosmetics, etc.
Author Contributions
Conceptualization, Y.K.-K., D.I. and I.P.; methodology, I.P.; software, I.P.; formal analysis, I.P.; investigation, Y.K.-K. and I.P.; resources, D.I. and Y.K.-K.; data curation, I.P.; writing—original draft preparation, Y.K.-K.; writing—review and editing, D.I. and I.P.; supervision, D.I. and I.P.; project administration, Y.K.-K.; funding acquisition, D.I. and Y.K.-K. All authors have read and agreed to the published version of the manuscript.
Funding
This study is financed by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project NO. BG-RRP-2.004-0009-C02.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Data will be available after reasonable request.
Conflicts of Interest
The authors declare no conflict of interest.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).