Redox Modulation of Meniere Disease by Coriolus Versicolor Treatment, a Nutritional Mushroom Approach with Neuroprotective Potential.

BACKGROUND: Meniere's disease (MD) is a cochlear neurodegenerative disease. Hearing loss appears to be triggered by oxidative stress in the ganglion neurons of the inner ear. OBJECTIVE: Here, we confirm the variation of markers of oxidative stress and inflammation in patients with Meniere and hypothesize that chronic treatment with Coriolus mushroom helps in the response to oxidative stress and acts on α-synuclein and on NF-kB-mediated inflammatory processes. METHODS: Markers of oxidative stress and inflammation were evaluated in MD patients with or without Coriolus treatment for 3 or 6 months. RESULTS: MD patients had a small increase in Nrf2, HO-1, γ-GC, Hsp70, Trx and sirtuin-1, which were further increased by Coriolus treatment, especially after 6 months. Increased markers of oxidative damage, such as protein carbonyls, HNE, and ultraweak chemiluminescence, associated with a decrease in plasma GSH/GSSG ratio, were also observed in lymphocytes from MD patients. These parameters were restored to values similar to the baseline in patients treated with Coriolus for both 3 and 6 months. Furthermore, treated MD subjects showed decreased expression of α-synuclein, GFAP and Iba-1 proteins and modulation of the NF-kB pathway, which were impaired in MD patients. These changes were greatest in subjects taking the supplements for 6 months. CONCLUSIONS: Our study suggests MD as a model of cochlear neurodegenerative disease for the identification of potent inducers of the Nrf2-vitagene pathway, able to reduce the deleterious consequences associated with neurodegenerative damage, probably by indirectly acting on α-synuclein expression and on inflammatory processes NF- kB-mediated.

Antioxidants, Hormetic Nutrition, and Autism.

Autism spectrum disorder (ASD) includes a heterogeneous group of complex neurodevel opmental disorders characterized by atypical behaviors with two core pathological manifestations: deficits in social interaction/communication and repetitive behaviors, which are associated with disturbed redox homeostasis. Modulation of cellular resilience mechanisms induced by low levels of stressors represents a novel approach for the development of therapeutic strategies, and in this context, neuroprotective effects of a wide range of polyphenol compounds have been demonstrated in several in vitro and in vivo studies and thoroughly reviewed by [2, 3]. Mushrooms have been used in traditional medicine for many years and have been associated with a long list of therapeutic properties, including antitumor, immunomodulatory, antioxidant, antiviral, antibacterial, and hepatoprotective effects [4]. Our recent studies have strikingly indicated the presence of polyphenols in nutritional mushrooms and demonstrated their protective effects in different models of neurodegenerative disorders in humans and rats [5, 6]. Although their therapeutic effects are exerted through multiple mechanisms, increasing attention is focusing on their capacity to induce endogenous defense systems by modulating cellular signaling processes, such as nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) pathways. Here we discuss the protective role of hormesis and its modulation by hormetic nutrients in ASD.

Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology.

The scientific community, recently, has focused notable attention on the chemopreventive and therapeutic effects of dietary polyphenols for human health. Emerging evidence demonstrates that polyphenols, flavonoids and vitamins counteract and neutralize genetic and environmental stressors, particularly oxidative stress and inflammatory process closely connected to cancer initiation, promotion and progression. Interestingly, polyphenols can exert antioxidant or pro-oxidant cytotoxic effects depending on their endogenous concentration. Notably, polyphenols at high dose act as pro-oxidants in a wide type of cancer cells by inhibiting Nrf2 pathway and the expression of antioxidant vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), GPx, heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system which play an essential role in the metabolism of reactive oxygen species (ROS), detoxification of xenobiotics and inhibition of cancer progression, by inducing apoptosis and cell cycle arrest according to the hormesis approach. Importantly, mutagenesis of Nrf2 pathway can exacerbate its "dark side" role, representing a crucial event in the initiation stage of carcinogenesis. Herein, we review the hormetic effects of polyphenols and nanoincapsulated-polyphenols in chemoprevention and treatment of brain tumors via activation or inhibition of Nrf2/vitagenes to suppress carcinogenesis in the early stages, and thus inhibit its progression. Lastly, we discuss innovative preclinical approaches through mini-brain tumor organoids to study human carcinogenesis, from basic cancer research to clinical practice, as promising tools to recapitulate the arrangement of structural neuronal tissues and biological functions of the human brain, as well as test drug toxicity and drive personalized and precision medicine in brain cancer.

Moringa oleifera Protects SH-SY5YCells from DEHP-Induced Endoplasmic Reticulum Stress and Apoptosis.

Moringa oleifera (MO) is a medicinal plant that has been shown to possess antioxidant, anticarcinogenic and antibiotic activities. In a rat model, MO extract (MOe) has been shown to have a protective effect against brain damage and memory decline. As an extending study, here, we have examined the protective effect of MOe against oxidative stress and apoptosis caused in human neuroblastome (SH-SY5Y) cells by di-(2-ethylhexyl) phthalate (DEHP), a plasticizer known to induce neurotoxicity. Our data show that MOe prevents oxidative damage by lowering reactive oxygen species (ROS) formation, restoring mitochondrial respiratory chain complex activities, and, in addition, by modulating the expression of vitagenes, i.e., antioxidant proteins Nrf2 and HO-1. Moreover, MOe prevented neuronal damage by partly inhibiting endoplasmic reticulum (ER) stress response, as indicated by decreased expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and Glucose-regulated protein 78 (GRP78) proteins. MOe also protected SH-SY5Y cells from DEHP-induced apoptosis, preserving mitochondrial membrane permeability and caspase-3 activation. Our findings provide insight into understanding of molecular mechanisms involved in neuroprotective effects by MOe against DEHP damage.