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Glial cell monoamine oxidase (MAO) activity has been implicated as a contributor to oxidative neuronal damage associated with various neurodegenerative diseases. The attenuation of MAO activity may provide protection against oxidative neurodegeneration. In this investigation, the presence of MAO-B in rat C6 astrocyte cells was substantiated by dose-dependent inhibition of enzyme activity in the presence of chlorgyline-HCl and L-deprenyl. The present study evaluated various dietary-derived food constituents for evidence of inhibition on oxidative deamination of monoamines or peroxide radical trapping capacity. Results of this investigation indicate that compounds which inhibit C6 glial cell MAO enzyme activity or scavenge peroxide product include chlorogenic acid, (+)-catechin, taxifolin, (-)-epigallocatechin gallate (EGCG), fisetin, coenzyme Q0, curcumin, sesamol, morin, sesame oil, silymarin, green tea, ferulic acid, caffeic acid, and rutin hydrate. The results of this study indicate that dietary compounds can attenuate peroxide production in glial cells by either inhibiting the deamination of monoamines or acting as a free radical scavenger.

The Nrf2-Keap1-ARE pathway is the principal regulator of antioxidant and phase II detoxification genes. Its activation increases the expression of antioxidant and cytoprotective proteins, protecting cells against infections. Nrf2 modulates virus-induced oxidative stress, ROS generation, and disease pathogenesis, which are vital in the viral life cycle. During respiratory viral infections, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an inflammatory process, and oxidative stress of the epithelium lining cells activate the transcription factor Nrf2, which protects cells from oxidative stress and inflammation. Nrf2 reduces angiotensin-converting enzyme 2 (ACE2) receptors expression in respiratory epithelial cells. SARS-CoV2 has a high affinity for ACE2 that works as receptors for coronavirus surface spike glycoprotein, facilitating viral entry. Disease severity may also be modulated by pre-existing conditions, such as impaired immune response, obesity, and age, where decreased level of Nrf2 is a common feature. Consequently, Nrf2 activators may increase Nrf2 levels and enhance antiviral mediators’ expression, which could initiate an “antiviral state”, priming cells against viral infection. Therefore, this hypothesis paper describes the use of flavonoid supplements combined with vitamin D3 to activate Nrf2, which may be a potential target to prevent and/or decrease SARS-CoV-2 infection severity, reducing oxidative stress and inflammation, enhancing innate immunity, and downregulating ACE2 receptors.

Manganese (Mn) is an essential trace element required for normal function and development. However, exposure to this metal at elevated levels may cause manganism, a progressive neurodegenerative disorder with neurological symptoms similar to idiopathic Parkinson’s disease (IPD). Elevated body burdens of Mn from exposure to parental nutrition, vapors in mines and smelters and welding fumes have been associated with neurological health concerns. The underlying mechanism of Mn neurotoxicity remains unclear. Accordingly, the present study was designed to investigate the toxic effects of Mn2+ in human neuroblastoma SH-SY5Y cells. Mn2+ caused a concentration dependent decrease in SH-SY5Y cellular viability compared to controls. The LD50 value was 12.98 μM Mn2+ (p <0.001 for control vs. 24h Mn treatment). Both TUNEL and annexin V/propidium iodide apoptosis assays confirmed the induction of apoptosis in the cells following exposure to Mn2+ (2 μM, 62 μM or 125 μM). In addition, Mn2+ induced both the formation and accumulation of DNA single strand breaks (via alkaline comet assay analysis) and oxidatively modified thymine bases (via gas chromatography/mass spectrometry analysis). Pre-incubation of the cells with characteristic antioxidants, either 1 mM N-acetylcysteine or 1 mM glutathione reduced the level of DNA strand breaks and the formation of thymine base lesions, suggesting protection against oxidative cellular damage. Our findings indicate that 1) exposure of SH-SY5Y cells to Mn promotes both the formation and accumulation of oxidative DNA nucleotide base damage, 2) SH-SY5Y cells with accumulated DNA damage are more likely to die via an apoptotic pathway and 3) the accumulated levels of DNA damage can be abrogated by the addition of exogenous chemical antioxidants. This is the first known report of Mn2+-induction and antioxidant protection of thymine lesions in this SH-SY5Y cell line and contributes new information to the potential use of antioxidants as a therapeutic strategy for protection against Mn2+-induced oxidative DNA damage.

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Excessive nitric oxide (NO) production in the brain has been correlated with neurotoxicity and the pathogenesis of several neurodegenerative diseases. NO production from neuroglial cells surrounding neurons contributes significantly to the pathogenesis of these diseases. The suppression of NO production in these cells may be beneficial in retarding many of these disorders. The present study was designed to evaluate the capacity of dietary-derived polyphenolic compounds, flavonoids, crude extracts, oils, and other food constituents in suppressing the release of NO from lipopolysaccharide (LPS)/gamma-interferon (IFN-gamma) stimulated C6 astrocyte cells. In this experiment, 61 compounds were tested, and 36 showed significant suppressive effects of NO production. The results indicate that the following compounds exhibited a dose-dependent suppressive effect of NO production with an IC50 less than 10(-3) M: quercetin, (-)-epigallocatechin gallate, morin, curcumin, apigenin, sesamol, chlorogenic acid, fisetin, (+)-taxifolin, (+)-catechin, ellagic acid, and caffeic acid. Compounds, which reduce NO production at less than 300 ppm, include milk thistle, silymarin, grapenol, and green tea. These results demonstrate a possible value for dietary compounds to inhibit the excessive production of NO.

African American Men are 65% more likely to develop prostate cancer and are twice as likely to die of prostate cancer, than are Caucasian American Males. The explanation for this glaring health disparity is still unknown; although a number of different plausible factors have been offered including genetic susceptibility and gene-environment interactions. We favor the hypothesis that altered gene expression plays a major role in the disparity observed in prostate cancer incidence and mortality between African American and Caucasian American Males. To discover genes or gene expression pattern(s) unique to African American or to Caucasian American Males that explain the observed prostate cancer health disparity in African American males, we conducted a micro array pilot project study that used prostate tumors with a Gleason score of 6. We compared gene expression profiling in tumors from African-American Males to prostate tumors in Caucasian American Males. A comparison of case-matched ratios revealed at least 67 statistically significant genes that met filtering criteria of at least +/- 4.0 fold change and p < 0.0001. Gene ontology terms prevalent in African American prostate tumor/normal ratios relative to Caucasian American prostate tumor/normal ratios included interleukins, progesterone signaling, Chromatin-mediated maintenance and myeloid dendritic cell proliferation. Functional in vitro assays are underway to determine roles that selected genes in these onotologies play in contributing to prostate cancer development and health disparity.