Investigating the effect of Echinacea purpurea on Nrf2 in Multiple Sclerosis by molecular docking method
Investigating the effect of Echinacea purpurea on Nrf2 in Multiple Sclerosis by molecular docking method
Melika Naderi,1,*
1. Islamic Azad University Pharmaceutical Sciences Branch
Introduction: Multiple Sclerosis (MS) is a chronic neuroinflammatory disease occurring in the central nervous system (CNS), characterized by demyelination, axonal degeneration and inflammatory lesions. Invading leukocytes produce exorbitant quantities of cytotoxic mediators, including reactive oxygen species (ROS), which shift the oxidant/pro-oxidant balance. In order to counteract these devastating effects, the nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in advancing defenses. Several studies have indicated that within MS lesions, Nrf2 is upregulated in macrophages and astrocytes, therefore, the expression of several antioxidative enzymes is also elevated.
Echinacea purpurea, commonly known as purple coneflower, contains substances that have shown promising effects on inflammatory responses, as well as immune cell functions. Furthermore, derivatives of this plant act as modulators in neuroprotective pathways that may be involved in pathogenesis of MS.
The objective of this study is to evaluate the binding affinity between Echinacea purpurea and Nrf2. It is expected that if they establish a strong connection, Echinacea purpurea is likely to promote the activation of Nrf2, subsequently reducing oxidative stress in MS.
Methods: In this research, initially, the Nrf2 structure was obtained from the Uniprot website, then necessary preparations, such as adding charge and hydrogen ions, were performed using Chimera software. The three-dimensional structure of the Echinacea purpurea was downloaded from the PubChem website. The binding site of the DISC1 protein was determined using Deepsite. [Center; X: 38.518, Y: -11.120, Z: 3.625 and Dimensions (Angstrom); X, Y, Z: 25.00] Finally, the molecular docking process was conducted using AutoDock Vina in PyRx 0.8 to assess the binding status of Echinacea purpurea to Nrf2.
Results: Following the completion of the docking process of Echinacea purpurea and Nrf2, using PyRx software, the obtained results are as followed. For each model, the data belongs to their binding affinity, RMSD lower bond and RMSD upper bound, respectively:
Model #1: [-8.9, 0.0, 0.0]
Model #2: [-8.9, 1.425, 2.595]
Model #3: [-8.5, 3.122, 9.59]
Model #4: [-8.4, 1.545, 2.931]
Model #5: [-8.1, 3.421, 9.413]
Conclusion: Based on the results of the molecular docking analysis of Echinacea purpurea and Nrf2, it was determined that in accordance with the negative binding energy, Echinacea purpurea can bind well to Nrf2. The efficacy of Echinacea purpurea in MS treatment requires further investigation; however, current research shows possibilities for utilizing this herbal medicine by targeting Nrf2 signaling pathways, due to its good binding status.