Like other organs, brain functions diminish with age. Furthermore, for a variety of neurological disorders—including Alzheimer’s disease—age is one of the higher-risk factors. Since in many Western countries the average age is increasing, determining approaches for decreasing the effects of aging on brain function is taking on a new urgency. Neuroinflammation and oxidative stress are two convoluted key factors in brain aging and chronic neurodegenerative diseases. The diverseness of factors, causing an age-related decrease in brain functions, requires identifying small molecules that have multiple biological activities that can affect all these factors. One great source of these small molecules is related to polyphenolic flavonoids. Recently, 3,3′,4′,7-tetrahydroxyflavone (fisetin) has been reported as a potent senotherapeutic capable of extending lifespan by reducing peroxidation levels and enhancing antioxidant cell responses. The neuroprotective effects of fisetin have been shown in several in vitro and in vivo models of neurological disorders due to its actions on multiple pathways associated with different neurological disorders. The present work aims to collect the most recent achievements related to the antioxidant and neuroprotective effects of fisetin. Moreover, in silico pharmacokinetics, pharmacodynamics, and toxicity of fisetin are also comprehensively described along with emerging novel drug delivery strategies for the amelioration of this flavonol bioavailability and chemical stability.

This study aimed to investigate the anti-inflammatory effects of Quantum Molecular Resonance (QMR) technology in an in vitro model of osteoarthritis-related inflammation. The study used THP-1-derived macrophages stimulated with lipopolysaccharide and hyaluronic acid fragments to induce the expression of inflammatory cytokines and nitrosative stress. QMR treatment inhibited COX-2 and iNOS protein expression and activity and reduced NF-κB activity. Furthermore, QMR treatment led to a significant reduction in peroxynitrite levels, reactive nitrogen species that can form during inflammatory conditions, and restored tyrosine nitration values to those similar to sham-exposed control cells. We also investigated the effect of QMR treatment on inflammasome activation and macrophage polarization in THP-1-derived macrophages. Results showed that QMR treatment significantly decreased NLRP3 and activated caspase-1 protein expression levels and downregulated IL-18 and IL-1β protein expression and secretion. Finally, our findings indicate that QMR treatment induces a switch in macrophage polarization from the M1 phenotype to the M2 phenotype.

‘Sulmona red garlic’ is an Italian variety characterized by a red tunica surrounding a white bulb. Red tunicae and non-commercial small bulbs are food wastes that must be studied for their added value. Hydroalcoholic extracts, obtained by separated inner and outer tunicae and peeled bulbs of small commercial ‘Sulmona red garlic’ bulbs, harvested at two different years, were first characterized with respect to their color, polyphenolic content, and antiradical activity. Then, an untargeted metabolic profile by means of electrospray ionization Fourier transform ion cyclotron resonance (ESI FT-ICR) mass spectrometry led to a comparative evaluation of the chemical diversity of six different samples. The study was completed by biological tests aiming to evaluate the associated health potential. Data on monocytes/macrophages showed good biocompatibility and a promising cytoprotective effect under oxidative stress conditions of all the extracts. At a molecular level, all the garlic extracts were able to downregulate the hydrogen peroxide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression through the modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) and peroxynitrite intracellular amounts, at different extents depending on the extract, the cell type, and the concentration. On the whole, data highlight an associated health potential of the extracts of this waste plant material both in terms of cytoprotection and of anti-inflammatory activity.