Computational study on the effectiveness of flavonoids from Marsilea crenata C. Presl as potent SIRT1 activators and NFκB Inhibitors

Abstract

Ovarian aging is a natural process in females, and it occurs due to an elevated ROS-induced inflammation caused by oxidative stress. SIRT-1 is a metabolic sensor that tightly regulates oxidative and inflammatory responses. However, this regulative function is antagonized by NFκB. Therefore, the objective of this study was to explore the pathways involved in aging and identify the flavonoid compounds from Marsilea crenata that might be useful as SIRT1 activators and NFκB inhibitors. The screening began with exploring the protein-protein interaction in the experimental process using BioGrid, and the role of the flavonoid was evaluated using STITCH. The interaction between hyperoside, luteolin, naringenin, and quercetin against SIRT1 and NFκB was determined through molecular docking, while their toxicity was also evaluated. The present result demonstrated that seven proteins were similar to the SIRT1 and NFκB pathways. The STITCH result showed six proteins involved in aging, and quercetin was shown to interact with SIRT1. The molecular docking result demonstrated that hyperoside exhibited as a SIRT1 activator for dimeric, heterodimeric, and heterotrimeric chains and NFκB inhibitor for p52-RelB, p50-p65 complex, and IκK, as it had the best binding affinity compared to the other flavonoids. These flavonoids also potentially have at least one toxicity characteristic. In conclusion, flavonoids from M. crenata might be a promising activator of SIRT1 and inhibitors of NFκB.