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.

This study aims at investigation of antibacterial property of Parthenium hysterophorous against aquatic bacterial pathogens and to identify the key bioactive compound of the same. Antibacterial activity of the crude extracts confirmed that chloroform extract PHC has strong antibacterial activity against aquatic pathogens V.anguillarum and V.harveyi with 16mm and 15mm ZOI at 1mg/well concentration. The crude extracts were subjected for GC-MS analysis to identify the secondary metabolites. PHC was subjected to silica-gel column chromatography to separate the individual phytochemicals. PHC was separated into 9 fractions, among which Fraction No.2 demonstrated significant antibacterial activity against V.anguillarum and V.harveyi with 19mm and 17mm ZOI at 10µg/well concentration. Fraction No.2 was identified to be β-sitosterol based on mass spectrometry analysis and fragmentation analysis. In-silico protein ligand docking demonstrated that β-sitosterol has highest affinity to inhibit dihydrofolate reductase (DHFR) enzyme with -10.10Kcal/mol binding energy. This prediction was further validated using molecular dynamic simulation for 20ns. Based on these computational analyses, it was proposed that β-sitosterol exhibits antibacterial activity via inhibition of DHFR enzyme. β-sitosterol is a well known nutritionally valuable compound that reduces cholesterol levels in humans. It is also been used as supplement feed to increase the nutritional value of cultured fishes. β-sitosterol has also been proven to have positive effect in growth and reproduction of cultivated fishes. Findings of this study strongly suggest the usage of β-sitosterol in aquaculture, as nutritional supplement and also as disease control agent to prevent and control fish diseases caused by Vibrio species.

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 β-Sitosterol as an effective α-Amylase inhibitory compound. Among the analysed fifteen phytochemicals, β-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 β-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 β-Sitosterol. The data obtained from MDS results strongly suggested the potential inhibitory impact of β-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 β-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 β-Sitosterol on α-Amylase inhibition to help the anti-diabetic potential of the phytocompound. Communicated by Ramaswamy H. Sarma

Streptomyces sp. DSM 115979T, isolated from soil collected in Lavasan (Iran), was classified as a novel subspecies of Streptomyces barkulensis, for which the name S. barkulensis subsp. lavasanensis subsp. nov. is proposed. Culture extracts yielded lavasamycin A (1) and B (2); their structures were elucidated by comprehensive HR-MS and NMR spectroscopic analyses, revealing a dihydroxyanthraquinone scaffold carrying a previously unreported N-acetyl-didesmethyl analogue of the aminodeoxysugar ossamine. Lavasamycin B (2) additionally features an unusual α,β-unsaturated γ-butenolide moiety. Lavasamycin A (1) exhibited antibacterial activity against Bacillus subtilis. Genome mining and comparative bioinformatic analyses identified the corresponding type II polyketide synthase biosynthetic gene cluster (BGC). Deletion of the ketosynthase genes lav31−lav32 abolished lavasamycin production, confirming the identity of the BGC. Inactivation of the TetR-family regulator gene lav34 resulted in substantially increased lavasamycin production, indicating pathway-specific transcriptional repression. Comparative analyses revealed similarities to angucycline and aminodeoxysugar biosynthetic pathways and enabled the proposal of a biosynthetic route to lavasamycin. In particular, the similarity of Lav15 to UrdM supports A-ring cleavage via Baeyer−Villiger oxidation. A spontaneous autoxidation likely converts 1 into 2. These findings expand the structural diversity of bacterial aromatic polyketides and highlight the biosynthetic potential of newly characterized Streptomyces taxa.