Alcohol Extracts From Ganoderma lucidum Delay the Progress of Alzheimer’s Disease by Regulating DNA Methylation in Rodents

Abstract

Age-related changes in methylation are involved in the occurrence and development of tumors, autoimmune disease, and nervous system disorders, including Alzheimer’s disease (AD), in elderly individuals; hence, modulation of these methylation changes may be an effective strategy to delay the progression of AD pathology. In this study, the AD model rats were used to screen the main active extracts from the mushroom, Ganoderma lucidum , for anti-aging properties, and their effects on DNA methylation were evaluated. The results of evaluation of rats treated with 100 mg/kg/day of D -galactose to induce accelerated aging showed that alcohol extracts of G. lucidum contained the main active anti-aging extract. The effects on DNA methylation of these G. lucidum extracts were then evaluated using SAMP8 and APP/PS1 AD model mice by whole genome bisulfite sequencing, and some methylation regulators including Histone H3, DNMT3A, and DNMT3B in brain tissues were up-regulated after treatment with alcohol extracts from G. lucidum . Molecular docking analysis was carried out to screen for molecules regulated by specific components, including ganoderic acid Mk, ganoderic acid C6, and lucidone A, which may be active ingredients of G. lucidum , including the methylation regulators of Histone H3, MYT, DNMT3A, and DNMT3B. Auxiliary tests also demonstrated that G. lucidum alcohol extracts could improve learning and memory function, ameliorate neuronal apoptosis and brain atrophy, and down-regulate the expression of the AD intracellular marker, Aβ 1-42 . We concluded that alcohol extracts from G. lucidum , including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression.

Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERK/NRF2 Signaling Pathway

“…Oxidative stress is an important factor that causes cellular senescence and body aging, and high concentrations of ROS trigger DNA damage and lead to cellular senescence through the direct or indirect regulation of aging-related signaling pathways [39]. As described in previous studies [16][17][18], Ganoderma lucidum could exert antiaging effects by regulating oxidative stress. In the present study, a senescent hAMSC cell model subjected to oxidative stress was established in vitro using H 2 O 2 .…”

Ganoderma lucidum Rhodiola compound preparation prevent d-galactose-induced immune impairment and oxidative stress in aging rat model

“…The main purpose of the Morris water maze experiment is to evaluate the cognitive function and spatial memory function of rats. A study by Lai showed that the use of Ganoderma lucidum extract can increase the weight of aging rats 24 . Our experimental results show that normal rats have significant weight gain and d-galactose can affect normal physiological functions of rats.…”

Epigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease

“…SAM reduces the production of Aβ and tau phosphorylation by upregulating PSEN1 and BACE1 expression in vivo, which improves the cognitive status in AD mouse models (162). The treatment with alcohol extracts from G. lucidum increases methylation regulators and improves memory in APP/PS1 AD model mice (163). In AD and mild cognitive impairment patients, B vitamin intake results in hypermethylation of NUDT15 and TXNRD1, which is associated with better cognitive performance (164).…”