Smilagenin induces expression and epigenetic remodeling of BDNF in alzheimer's disease
文献类型：期刊论文
| 作者 | Yang, Shuangshuang1,2,3,4,5 ; Fan, Lei1,5; Zhang, Rui1,5; Song, Chenghuan1,5; Shi, Jiyun1,5; Wang, Jing1,5; Zhang, Pingao1,5; Wang, Hao1,5; Zhang, Yongfang1,5
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| 刊名 | PHYTOMEDICINE
 |
| 出版日期 | 2023-09-01 |
| 卷号 | 118页码:11 |
| 关键词 | Alzheimer's disease Brain-derived neurotrophic factor Histone acetylation Smilagenin |
| ISSN号 | 0944-7113 |
| DOI | 10.1016/j.phymed.2023.154956 |
| 通讯作者 | Wang, Hao(angela_wanghao@sjtu.edu.cn) ; Zhang, Yongfang(13391269883@163.com) |
| 英文摘要 | Background: Smilagenin (SMI) is a lipid-soluble steroidal sapogenin, extracted from traditional Chinses medicinal herbs Radix Asparagi, which is extracted from the dry root of Asparagus cochinchinensis (Lour.) Merr. We previously found that SMI significantly increased brain-derived neurotrophic factor (BDNF) expression in A beta-intoxicated SH-SY5Y cells. Methods: In this study, we performed behavioral tests to analyze cognitive function of WT and APP/PS1 mice treated with or without SMI, and found that SMI could significantly improve the learning and memory ability of APP/PS1 mice. Moreover, immunofluorescence and ELISA results showed that SMI pretreatment could effectively reduce the deposition of eta-amyloid plaques in the cortex and hippocampus of APP/PS1 mice (26 mg/kg/ day for 60 days) and inhibit the secretion of A & beta;1-42 in N2a/APPswe cells (10 & mu;M concentration for 24 hours). Results: Mechanistically, SMI enhanced BDNF mRNA expression, elevated the global level of H3AC and H4AC, and increased the expression of P300 in AD models. Furthermore, chromatin immunoprecipitation results showed that SMI could increase the levels of H3AC and H4AC at the promoter of BDNF promoter II and IV, indicating that SMI epigenetically regulates BDNF expression through HAT enhancement. To further verify the critical role of P300 by which SMI upregulated histone acetylation in BDNF, AD mice were treated with SMI and C646 simultaneously. Behavioral experiments showed that the improvement effects of SMI on cognitive impairment were abolished after P300 inhibition in APP/PS1 mice. Conclusions: Our research for the first time demonstrated that SMI showed neuroprotective effects by increasing the expression of P300 protein, thus upregulating histone acetylation levels in the promoter region of BDNF and promoting its transcription. Our findings provide an important theoretical basis for the treatment of Alzheimer's disease with SMI extracted from Asparagus cochinchinensis (Lour.) Merr. |
| WOS关键词 | HISTONE ACETYLATION ; SYNAPTIC PLASTICITY ; MESSENGER-RNA ; MOUSE MODEL ; MEMORY ; DYSREGULATION ; HIPPOCAMPUS ; DEACETYLASE ; INHIBITORS ; HDAC2 |
| 资助项目 | National Natural Science Foundation of China[82003710] ; National Natural Science Foundation of China[81573401] ; National Natural Science Foundation of China[81973297] ; Shanghai High Level Local Colleges Construction Project[XD18015] ; Key project of Shanghai Science and Technology Commission[19JC1413100] ; Research Foundation of Translational Medicine, Shanghai Jiao Tong University[ZH2018ZDA23] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001047099200001 |
| 出版者 | ELSEVIER GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306986]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Hao; Zhang, Yongfang |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Dept Pharmacol & Chem Biol, Sch Med, Shanghai 200025, Peoples R China 2.Shanghai Xuhui Cent Hosp, Cent Lab, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Shanghai Engn Res Ctr Phase I Clin Res & Qual Cons, Shanghai 200031, Peoples R China 5.Shanghai Jiao Tong Univ, Shanghai Univ Collaborat Innovat Ctr Translat Med, Sch Med, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Shuangshuang,Fan, Lei,Zhang, Rui,et al. Smilagenin induces expression and epigenetic remodeling of BDNF in alzheimer's disease[J]. PHYTOMEDICINE,2023,118:11. |
| APA | Yang, Shuangshuang.,Fan, Lei.,Zhang, Rui.,Song, Chenghuan.,Shi, Jiyun.,...&Zhang, Yongfang.(2023).Smilagenin induces expression and epigenetic remodeling of BDNF in alzheimer's disease.PHYTOMEDICINE,118,11. |
| MLA | Yang, Shuangshuang,et al."Smilagenin induces expression and epigenetic remodeling of BDNF in alzheimer's disease".PHYTOMEDICINE 118(2023):11. |
入库方式： OAI收割
来源：上海药物研究所
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