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.

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Actinomycetes are gram-positive bacteria that have a high GC content compared to their counterparts. Actinomycetes were capable of producing a broad range of secondary metabolites and many of these were anti-bacterial agents. Antibiotics have been known to play a vital role in therapeutics and the clinical management of various diseases. Actinomycetes have contributed more than 70% of known antibiotics in the market today. Apart from antibiotics, actinomycetes also produce several enzymes, enzyme inhibitors, anticancer and anti-diabetic secondary metabolites. Currently, actinomycetes are being studied for medicinal, pharmaceutical, industrial, environmental and bioremediation applications. The current study focuses on a variety of antibacterial agents derived from actinomycetes and new antibiotics under clinical trial along with their mode of action. It also describes the genome mining methods for screening actinomycetes isolates for biosynthetic gene clusters and specific antibacterial secondary metabolites.