In-silico study of Marselia crenata compounds as activator Keap1/Nrf2 pathway in ovarian function

Abstract

Abstract The activity of granulosa cells during folliculogenesis and the presence of follicular atresia causes increased ROS (Reactive Oxygen spesies) level in the ovaries. ROS accumulation will induce disorders of ovarian physiology, so maintaining ROS levels is necessary for normal ovarian physiology. Nrf2 (nuclear factor erythroid-2-related factor 2) is a protein that plays a role in regulating the expression of genes that induce antioxidant expression. In an inactive, Nrf2 binds to Keap1 in the cytoplasm. Inhibiting the interaction of Keap1-Nrf2 will activate Nrf2 and Nrf2 will move towards the nucleus to regulate some endogenous antioxidants. The research aims to investigate the potential of Marsilea crenata compounds as inhibitors of Keap1-Nrf2 interactions. The study used an in-silico approach. Compounds chosen were Naringenin and Hyperosida. Keap1 (ID: 2flu) was obtained from Protein Data Bank (PDB), while Hyperoside (CID: 5281643), and Naringenin (CID: 932) were retrieved from PubChem database. Keap1 was prepared by removing any solvents and other ligands using Discovery Studio v.19 versions. Naringenin and Hyperoside were minimized their affinity using PyRx 0.8 software. Ligand and protein were interacted using autodock vina integrated with PyRx 0.8 tools and visualized by Discovery Studio v.19. Results showed that Naringenin and Hyperoside bound to Keap1 in the same active sites of Keap1- Nrf2 regions. Both of Naringenin and Hyperoside interacted with Keap1 in different areas. The interaction between Keap1 and ligands (Naringenin and Hyperoside) was through the formation of hydrogen bonds and Van der walls forces. The binding energy of Naringenin and Hyperoside with Keap1 was -6.7 and -7.2 Kcal/mol, respectively. Our study predicted that Naringenin and Hyperoside might have a potential activity to inhibit Keap1-Nrf2 interaction and activated Nrf2 to regulate the antioxidant gene.