Naufal Kushairi

Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Lewy body dementia, etc. Alzheimer’s Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer’s Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer’s Disease.

Oxidative stress and inflammation in neuron-glia system are key factors in the pathogenesis of neurodegenerative diseases. As synthetic drugs may cause side effects, natural products have gained recognition for the prevention or management of diseases. In this study, hot water (HE-HWA) and ethanolic (HE-ETH) extracts of the basidiocarps of Hericium erinaceus mushroom were investigated for their neuroprotective and anti-inflammatory activities against hydrogen peroxide (H₂O₂)-induced neurotoxicity in HT22 mouse hippocampal neurons and lipopolysaccharide (LPS)-induced BV2 microglial activation respectively. HE-ETH showed potent neuroprotective activity by significantly (p < 0.0001) increasing the viability of H₂O₂-treated neurons. This was accompanied by significant reduction in reactive oxygen species (ROS) (p < 0.05) and improvement of the antioxidant enzyme catalase (CAT) (p < 0.05) and glutathione (GSH) content (p < 0.01). Besides, HE-ETH significantly improved mitochondrial membrane potential (MMP) (p < 0.05) and ATP production (p < 0.0001) while reducing mitochondrial toxicity (p < 0.001), Bcl-2-associated X (Bax) gene expression (p < 0.05) and nuclear apoptosis (p < 0.0001). However, gene expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were unaffected (p > 0.05). HE-ETH also significantly (p < 0.0001) reduced nitric oxide (NO) level in LPS-treated BV2 indicating an anti-inflammatory activity in the microglia. These findings demonstrated HE-ETH maybe a potential neuroprotective and anti-inflammatory agent in neuron-glia environment.