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Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease.
Neurobiol Aging. 2015 May; 36(5):1792-807.NA

Abstract

Alzheimer's disease (AD) is characterized by amyloid β (Aβ) peptide aggregation and cholinergic neurodegeneration. Therefore, in this paper, we examined silibinin, a flavonoid extracted from Silybum marianum, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for AD treatment. To achieve this, we used molecular docking and molecular dynamics simulations to examine the affinity of silibinin with Aβ and AChE in silico. Next, we used circular dichroism and transmission electron microscopy to study the anti-Aβ aggregation capability of silibinin in vitro. Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay, immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun experiment were performed on silibinin-treated APP/PS1 transgenic mice. In molecular dynamics simulations, silibinin interacted with Aβ and AChE to form different stable complexes. After the administration of silibinin, AChE activity and Aβ aggregations were down-regulated, and the quantity of AChE also decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater scores in the Morris Water Maze. Moreover, silibinin could increase the number of newly generated microglia, astrocytes, neurons, and neuronal precursor cells. Taken together, these data suggest that silibinin could act as a dual inhibitor of AChE and Aβ peptide aggregation, therefore suggesting a therapeutic strategy for AD treatment.

Authors+Show Affiliations

Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Guangzhou Brain and Psychiatric Hospital, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Key Lab of High Performance Computing of Guangdong Province, Guangzhou, China.Research Center for Drug Discovery and Institute of Human Virology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.Department of Anatomy, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address: gu_huaiyu@yahoo.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25771396

Citation

Duan, Songwei, et al. "Silibinin Inhibits Acetylcholinesterase Activity and Amyloid Β Peptide Aggregation: a Dual-target Drug for the Treatment of Alzheimer's Disease." Neurobiology of Aging, vol. 36, no. 5, 2015, pp. 1792-807.
Duan S, Guan X, Lin R, et al. Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease. Neurobiol Aging. 2015;36(5):1792-807.
Duan, S., Guan, X., Lin, R., Liu, X., Yan, Y., Lin, R., Zhang, T., Chen, X., Huang, J., Sun, X., Li, Q., Fang, S., Xu, J., Yao, Z., & Gu, H. (2015). Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease. Neurobiology of Aging, 36(5), 1792-807. https://doi.org/10.1016/j.neurobiolaging.2015.02.002
Duan S, et al. Silibinin Inhibits Acetylcholinesterase Activity and Amyloid Β Peptide Aggregation: a Dual-target Drug for the Treatment of Alzheimer's Disease. Neurobiol Aging. 2015;36(5):1792-807. PubMed PMID: 25771396.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease. AU - Duan,Songwei, AU - Guan,Xiaoyin, AU - Lin,Runxuan, AU - Liu,Xincheng, AU - Yan,Ying, AU - Lin,Ruibang, AU - Zhang,Tianqi, AU - Chen,Xueman, AU - Huang,Jiaqi, AU - Sun,Xicui, AU - Li,Qingqing, AU - Fang,Shaoliang, AU - Xu,Jun, AU - Yao,Zhibin, AU - Gu,Huaiyu, Y1 - 2015/02/11/ PY - 2014/04/29/received PY - 2015/02/03/revised PY - 2015/02/04/accepted PY - 2015/3/16/entrez PY - 2015/3/17/pubmed PY - 2016/3/2/medline KW - APP/PS1 transgenic mice KW - Acetylcholinesterase KW - Alzheimer's disease KW - Amyloid β protein KW - MD simulation KW - Memory deficits KW - Silibinin SP - 1792 EP - 807 JF - Neurobiology of aging JO - Neurobiol Aging VL - 36 IS - 5 N2 - Alzheimer's disease (AD) is characterized by amyloid β (Aβ) peptide aggregation and cholinergic neurodegeneration. Therefore, in this paper, we examined silibinin, a flavonoid extracted from Silybum marianum, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for AD treatment. To achieve this, we used molecular docking and molecular dynamics simulations to examine the affinity of silibinin with Aβ and AChE in silico. Next, we used circular dichroism and transmission electron microscopy to study the anti-Aβ aggregation capability of silibinin in vitro. Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay, immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun experiment were performed on silibinin-treated APP/PS1 transgenic mice. In molecular dynamics simulations, silibinin interacted with Aβ and AChE to form different stable complexes. After the administration of silibinin, AChE activity and Aβ aggregations were down-regulated, and the quantity of AChE also decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater scores in the Morris Water Maze. Moreover, silibinin could increase the number of newly generated microglia, astrocytes, neurons, and neuronal precursor cells. Taken together, these data suggest that silibinin could act as a dual inhibitor of AChE and Aβ peptide aggregation, therefore suggesting a therapeutic strategy for AD treatment. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/25771396/Silibinin_inhibits_acetylcholinesterase_activity_and_amyloid_β_peptide_aggregation:_a_dual_target_drug_for_the_treatment_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(15)00102-5 DB - PRIME DP - Unbound Medicine ER -