Lai Guoxiao, Guo Yinrui, Chen Diling, Tang Xiaocui, Shuai Ou, Yong Tianqiao, Wang Dongdong, Xiao Chun, Zhou Gailian, Xie Yizhen, Yang Burton B, Wu Qingping
College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China.
State Key Laboratory of Applied Microbiology Southern China - Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application - Guangdong Open Laboratory of Applied Microbiology - Guangdong Institute of Microbiology, Guangzhou, China.
Front Pharmacol. 2019 Mar 26;10:272. doi: 10.3389/fphar.2019.00272. eCollection 2019.
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, , 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 contained the main active anti-aging extract. The effects on DNA methylation of these 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 . 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 , including the methylation regulators of Histone H3, MYT, DNMT3A, and DNMT3B. Auxiliary tests also demonstrated that 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. We concluded that alcohol extracts from , including ganoderic acid and lucidone A, are the main extracts involved in delaying AD progression.
甲基化的年龄相关变化与老年人肿瘤、自身免疫性疾病及神经系统疾病（包括阿尔茨海默病（AD））的发生和发展有关；因此，调节这些甲基化变化可能是延缓AD病理进程的有效策略。在本研究中，使用AD模型大鼠筛选蘑菇的主要活性提取物以评估其抗衰老特性，并评价其对DNA甲基化的影响。用100mg/kg/天的D-半乳糖诱导加速衰老的大鼠的评估结果表明，[蘑菇名称未给出]的醇提取物含有主要的活性抗衰老提取物。然后通过全基因组亚硫酸氢盐测序，使用SAMP8和APP/PS1 AD模型小鼠评估这些提取物对DNA甲基化的影响，用[蘑菇名称未给出]的醇提取物处理后，脑组织中的一些甲基化调节因子，包括组蛋白H3、DNMT3A和DNMT3B上调。进行分子对接分析以筛选由特定成分调节的分子，包括灵芝酸Mk、灵芝酸C6和光泽三萜酸A，这些可能是[蘑菇名称未给出]的活性成分，包括组蛋白H3、MYT、DNMT3A和DNMT3B的甲基化调节因子。辅助试验还表明，[蘑菇名称未给出]醇提取物可改善学习和记忆功能，减轻神经元凋亡和脑萎缩，并下调AD细胞内标志物Aβ的表达。我们得出结论，[蘑菇名称未给出]的醇提取物，包括灵芝酸和光泽三萜酸A，是参与延缓AD进展的主要提取物。
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