ß-Sitosterol, a phytocompound from Parthenium hysterophorus, reveals anti-diabetic properties through α-Amylase inhibition: an in-silico and in-vitro analysis.

The study aims to identify and validate a potential α-Amylase inhibitor from the leaf extract of the Parthenium hysterophorus. Molecular docking and dynamics analyses were performed to test the anti-diabetic efficacy of the compound by focusing on α-Amylase inhibition. The molecular docking study using AutoDock Vina (PyRx) and SeeSAR tools identified ß-Sitosterol as an effective α-Amylase inhibitory compound. Among the analysed fifteen phytochemicals, ß-Sitosterol demonstrated the most appreciable binding energy (-9.0 Kcal/mol) and is comparatively higher than the binding energy of the standard α-Amylase inhibitor, the Acarbose (-7.6 Kcal/mol). The significance of the interaction between ß-Sitosterol and α-Amylase was further investigated using Molecular Dynamics Simulation (MDS) for 100 ns via GROMACS. The data reveals that the compound could exhibit the highest stability with α-Amylase regarding RMSD, RMSF, SASA and Potential Energy analysis. The key residue of α-Amylase (Asp -197) shows a significantly low fluctuation of 0.7 Å while interacting with ß-Sitosterol. The data obtained from MDS results strongly suggested the potential inhibitory impact of ß-Sitosterol on α-Amylase. In addition, the proposed phytochemical was purified from the leaf extracts of P.hysterophorus using the silica gel column chromatography and identified by GC-MS analysis. The purified ß-Sitosterol demonstrated a significant 42.30% in-vitro α-Amylase enzyme inhibition property under 400 µg/ml concentration and thus supported the in-silico predictions. Further in-vivo investigations are necessary to analyse the efficiency of ß-Sitosterol on α-Amylase inhibition to help the anti-diabetic potential of the phytocompound.Communicated by Ramaswamy H. Sarma.

Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation.

Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in the body. Nuclear factor E2-related factor 2 (NRF2), encoded by the gene NFE2L2, is the master regulator of phase II antioxidant enzymes that protect against oxidative stress and inflammation. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer. The consumption of dietary phytochemicals acts as an effective modulator of NRF2/ARE in various acute and chronic diseases. In the present review, we discussed the role of NRF2 in diabetes, Alzheimer's disease (AD), Parkinson's disease (PD), cancer, and atherosclerosis. Additionally, we discussed the phytochemicals like curcumin, quercetin, resveratrol, epigallocatechin gallate, apigenin, sulforaphane, and ursolic acid that have effectively modified NRF2 signaling and prevented various diseases in both in vitro and in vivo models. Based on the literature, it is clear that dietary phytochemicals can prevent diseases by (1) blocking oxidative stress-inhibiting inflammatory mediators through inhibiting Keap1 or activating Nrf2 expression and its downstream targets in the nucleus, including HO-1, SOD, and CAT; (2) regulating NRF2 signaling by various kinases like GSK3beta, PI3/AKT, and MAPK; and (3) modifying epigenetic modulation, such as methylation, at the NRF2 promoter region; however, further investigation into other upstream signaling molecules like NRF2 and the effect of phytochemicals on them still need to be investigated in the near future.