In Silico Molecular Docking Analysis of Nigella Sativa Bioactive Compounds as Potential Modulators of WNT/Β-Catenin Pathway Proteins in Chronic Venous Insufficiency

Abstract

Chronic venous insufficiency (CVI) is a vascular disease in which there is obstruction in the flow of venous blood either in the superficial vein or in the deep veins, which causes venous hypertension due to the development of reflux and inflammation. Recent research has emphasized the role of the WNT/β-catenin signaling pathway in the physiopathology of CVI. The aim of this in silico study is to explore the binding potential of two important bioactive molecules (carvacrol & thymoquinone) from Nigella sativa with WNT-related proteins (FZD2, DVL2, and AXIN1) underlying the pathology of venous insufficiency. Further proof of the highly functional interplay between FZD2, DVL2, and AXIN1 was provided through protein-protein interaction analysis using STRING, thereby justifying their selection as the major molecular targets. The docking study revealed that both carvacrol and thymoquinone showed a promising binding affinity towards the target molecules, especially AXIN1. The carvacrol-AXIN1 complex exhibited a better geometric complementarity value of -13.86 AC, as well as the binding free energy of -6.13 kcal/mol. Although thymoquinone had similar thermodynamic stability, carvacrol possessed a better fit in terms of geometric complementarity within the AXIN1. These findings suggest that the minor discrepancies may not establish therapeutic superiority for chronic venous insufficiency. The present in-silico study serves as a basis for future hypothesis-driven research on the therapeutic effects of such molecules in vascular diseases.