Nutritional Mushroom Treatment in Meniere’s Disease with Coriolus versicolor: A Rationale for Therapeutic Intervention in Neuroinflammation and Antineurodegeneration

Abstract

Meniere’s disease (MD) represents a clinical syndrome characterized by episodes of spontaneous vertigo, associated with fluctuating, low to medium frequencies sensorineural hearing loss (SNHL), tinnitus, and aural fullness affecting one or both ears. To date, the cause of MD remains substantially unknown, despite increasing evidence suggesting that oxidative stress and neuroinflammation may be central to the development of endolymphatic hydrops and consequent otholitic degeneration and displacement in the reuniting duct, thus originating the otolithic crisis from vestibular otolithic organs utricle or saccule. As a starting point to withstand pathological consequences, cellular pathways conferring protection against oxidative stress, such as vitagenes, are also induced, but at a level not sufficient to prevent full neuroprotection, which can be reinforced by exogenous nutritional approaches. One emerging strategy is supplementation with mushrooms. Mushroom preparations, used in traditional medicine for thousands of years, are endowed with various biological actions, including antioxidant, immunostimulatory, hepatoprotective, anticancer, as well as antiviral effects. For example, therapeutic polysaccharopeptides obtained from Coriolus versicolor are commercially well established. In this study, we examined the hypothesis that neurotoxic insult represents a critical primary mediator operating in MD pathogenesis, reflected by quantitative increases of markers of oxidative stress and cellular stress response in the peripheral blood of MD patients. We evaluated systemic oxidative stress and cellular stress response in MD patients in the absence and in the presence of treatment with a biomass preparation from Coriolus. Systemic oxidative stress was estimated by measuring, in plasma, protein carbonyls, hydroxynonenals (HNE), and ultraweak luminescence, as well as by lipidomics analysis of active biolipids, such as lipoxin A4 and F2-isoprostanes, whereas in lymphocytes we determined heat shock proteins 70 (Hsp72), heme oxygenase-1 (HO-1), thioredoxin (Trx), and γ-GC liase to evaluate the systemic cellular stress response. Increased levels of carbonyls, HNE, luminescence, and F2-isoprostanes were found in MD patients with respect to the MD plus Coriolus-treated group. This was paralleled by a significant (p < 0.01) induction, after Coriolus treatment, of vitagenes such as HO-1, Hsp70, Trx, sirtuin-1, and γ-GC liase in lymphocyte and by a significant (p < 0.05) increase in the plasma ratio-reduced glutathione (GSH) vs. oxidized glutathione (GSSG). In conclusion, patients affected by MD are under conditions of systemic oxidative stress, and the induction of vitagenes after mushroom supplementation indicates a maintained response to counteract intracellular pro-oxidant status. The present study also highlights the importance of investigating MD as a convenient model of cochlear neurodegenerative disease. Thus, searching innovative and more potent inducers of the vitagene system can allow the development of pharmacological strategies capable of enhancing the intrinsic reserve of vulnerable neurons, such as ganglion cells to maximize antidegenerative stress responses and thus providing neuroprotection.

Anti-inflammatory and Anti-oxidant Activity of Hidrox® in Rotenone-Induced Parkinson’s Disease in Mice

“…Nrf2, one of the most important transcription factors that activates several genes with cytoprotective function, participates in antioxidant and anti-inflammatory reactions [ 72 , 73 , 74 , 75 , 76 , 77 ]. These cytoprotective genes encode a wide variety of phase II detoxification enzymes, such as NAD (P) H: quinone oxidoreductase 1 (NQO1), HO-1, γ-GCS, glutathione S-transferase (GST) and glutamate-cysteine ligase, thioredoxin, thioredoxin reductase, thermal shock proteins and many others [ 31 , 78 , 79 , 80 , 81 ]. Cell culture studies have shown that HT was the only olive oil phenol capable of increasing the transactivation of Nrf2, which suggests that this polyphenol could be responsible for the induction of Nrf2-dependent gene expression [ 82 ].…”

Healthy Effects of Plant Polyphenols: Molecular Mechanisms

“…These effects represent a powerful instrument supporting redox homeostasis under stressful conditions [111] and support the assumptions that the helpful properties of polyphenols carry out through adaptive stress response vitagenes. Within this context, both heme oxygenase-1 (HO-1) and Hsp70 have received considerable attention for their recognized antioxidative function needed to maintain cell homeostasis [112]. Moreover, the well-known principle of hormesis may be applied also to HO-1.…”

Ozone: a natural bioactive molecule with antioxidant property as potential new strategy in aging and in neurodegenerative disorders

“…curcumin, resveratrol, flavonols present in Ginkgo biloba extracts, polyphenols present abundantly in the leaves and in the ripening fruits of the olive tree, Olea europaea ), as well as mushrooms ( Hericium Erinaceus , Coriolus versicolor ) can significantly modulate Nrf2 and Nrf2-dependent vitagenes expression, showing neuroprotective action. This can potentially resolve pathologies such as AD, PD and also Meniere’s Disease, another degenerative pathology ( Amara et al, 2020 , Trovato et al, 2016a , Trovato et al, 2016b , Trovato Salinaro et al, 2018 , Scuto et al, 2019 ).…”

“…Preconditioning is a process whereby an initial low dose of a stressor agent upregulates adaptive mechanisms that enhance resilience against subsequent and acute stressor agents within a time-sensitive window of ∼ 10–14 days ( Calabrese, 2016 ). Different studies demonstrated that the supplementation with Coriolus versicolor ( Ferreiro et al, 2018 , Scuto et al, 2019 , Trovato Salinaro et al, 2018 , Trovato et al, 2016a ), and Hericium Herinaceus ( Trovato Salinaro et al, 2018 , Trovato et al, 2016b ) biomass and polyphenols ( Mao et al, 2019 ) can maintain the response to neutralize intracellular pro-oxidant/neuroinflammatory status, preventing different neurological conditions.…”