Title : Hormetic nutrition with medicinal mushrooms in neurodegeneration: Redoxomics and metabolomics approaches from bench to clinic
Abstract:
Hormetic nutrition for enhancing stress resilience and overall human health, recently, have received much attention. Redoxomics has been successfully applied to study neurodegeneration of ganglion neurons of the inner ear for the identification of potential biomarkers and novel mechanisms of Meniere’s disease (MD) neurodegeneration and the assessment of treatment prognosis and outcome. The identification and quantification of diverse lipidic species in human urine by innovative mass spectrometry platforms is of considerable importance to study redox metabolic homeostasis in normal and pathofisiological conditions. To date, the cause of Meniere's disease remains substantially unknown, despite many study reports indicate idiopathic endolymphatic hydrops as the main pathophysiological event, and increasing evidence suggests that oxidative stress and neuroinflammation are central to the development of endolymphatic hydrops and consequent vestibular otholitic degeneration and crisis. Emerging evidence indicate that hormetic nutrients including mushrooms supplementation targeting Nrf2 pathway and stress resilience vitagenes have shown to improve neurotoxic insults and mitochondrial dysfunction thus inhibiting oxidative stress and neuroinflammation that trigger neurosensorial degeneration of spiral ganglion cells. In this study we showed increased levels of carbonyls, HNE and pro-inflammatory NF-kB pathway as well as reduced mitochondrial complex activities in MD patients with respect to MD plus Coriolus treated group for 6 months. According to hormesis, supplementation by mushrooms exhibits biphasic dose-response effects by upregulating at low dose the expression of HO-1, Hsp70, Sirt1, Y-GCs and Trx (P < 0.05) in lymphocytes of MD patients as compared to untreated MD patients and by a significant increase in the plasma ratio reduced glutathione (GSH) vs oxidized glutathione (GSSG) (P<0.05) as measure of antioxidant status to oxidative stress. Lipidomics showed a significant increase of bioactive eicosanoid lipoxin A4 in lymphocytes, plasma and urine of MD patients compared to controls as well as a significant reduction of pro-inflammatory eicosanoid F2-isoprostanes. Metabolomics approach and results will be also discussed. In conclusion, hormetic nutrients including Coriolus versicolor biomass supplementation targeting vitagenes could be considered a promising nutritional approach in healthy aging medicine and anti-neurodegenerative therapeutics for neuroprotection in order to prevent or inhibit neuroinflammation releated to oxidative stress-induced neurodegeneration of vulnerable ganglion neurons in MD patients and high risk of developing sensorineural hearing loss.