Key Mechanisms and Potential Implications of <i>Hericium erinaceus</i> in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease
Marika Cordaro,
Angela Trovato Salinaro,
Rosalba Siracusa,
Ramona D’Amico,
Daniela Impellizzeri,
Maria Scuto,
Maria Laura Ontario,
Salvatore Cuzzocrea,
Rosanna Di Paola,
Roberta Fusco,
Vittorio Calabrese
Affiliations
Marika Cordaro
Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy
Angela Trovato Salinaro
Department of Biomedical and Biotechnological Sciences, University of Catania, 95124 Catania, Italy
Rosalba Siracusa
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy
Ramona D’Amico
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy
Daniela Impellizzeri
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy
Maria Scuto
Department of Biomedical and Biotechnological Sciences, University of Catania, 95124 Catania, Italy
Maria Laura Ontario
Department of Biomedical and Biotechnological Sciences, University of Catania, 95124 Catania, Italy
Salvatore Cuzzocrea
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy
Rosanna Di Paola
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy
Roberta Fusco
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, 98166 Messina, Italy
Vittorio Calabrese
Department of Biomedical and Biotechnological Sciences, University of Catania, 95124 Catania, Italy
Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and Hericium erinaceus was administered daily by gavage. Before the experiment’s end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. Hericium erinaceus administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, Hericium erinaceus decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that Hericium erinaceus has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress.