Molecular Docking Studies to Understand the Potential Role of Ginger Compounds (6-Gingerol and 6-Shogaol) on Anti-Angiogenic and Anti-Lymphangiogenic Mechanisms

摘要

Background: 6-Gingerol and 6-Shogaol are novel biologically active phenol compounds isolated from rhizomes of Ginger (Zingiber officinale Roscoe), which has a potential role as anti-inflammatory, anti-oxidant and apoptotic. Till date there are no scientific reports on the functional properties of Ginger against the molecular mechanisms of angiogenesis, lymphangiogenesis, and metastasis. Hence, in the present study we have explored the feasibility of active ginger compounds (6-Gingerol and 6-Shogaol) to validate their molecular mechanisms on angiogenesis and lymphangiogenesis in breast cancer progression through in silico approach. Methodology: Studies have been targeted to find the interactions between selected protein receptors, which play a pivotal role in angiogenesis and lymphangiogenesis and ligands of Ginger compounds (6-Gingerol and 6-Shogaol) by using Accelrys discovery studio 2.5, followed by analysis of data.Results: Based on the in silico approaches, we found the best interactions between ginger compounds (6-Gingerol and 6-Shogaol) and targeted protein molecules as shown less than 3.10 A0H-bond distance to indicate higher binding affinity and stronger interactions and high docking scores. We demonstrate docking interactions of 6-Gingerol with the proteins involved in angiogenesis like VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B, Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3) and with the proteins involved in lymphangiogenesis such as VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ). Similarly, our data shows that 6-Shogaol also interacts with angiogenic specific proteins, like [VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B), Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3)] and lymphangiogenesis [VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ)].Discussion: In silico approaches suggest a stronger binding affinity between the ginger compounds (6-Gingerol and 6-Shogaol) and selected proteins critical in angiogenesis and lymphangiogenesis. The present study underlines the feasibility of neutraceuticals to target the pathways participating in breast cancer progression through neovascularization. Our results also advocate 6-Gingerol to be more potent inhibitor of lymphangiogenesis assessed by its binding efficacy with VEGF-C and NRP2 (4QDS) as compared against 6-Shogaol.