title: A Novel, Multi-Target Natural Drug Candidate, Matrine, Improves Cognitive Deficits in Alzheimer's Disease Transgenic Mice by Inhibiting Aβ Aggregation and Blocking the RAGE/Aβ Axis.
abstract: The treatment of AD is a topic that has puzzled researchers for many years. Current mainstream theories still consider Aβ to be the most important target for the cure of AD. In this study, we attempted to explore multiple targets for AD treatments with the aim of identifying a qualified compound that could both inhibit the aggregation of Aβ and block the RAGE/Aβ axis. We believed that a compound that targets both Aβ and RAGE may be a feasible strategy for AD treatment. A novel and small natural compound, Matrine (Mat), was identified by high-throughput screening of the main components of traditional Chinese herbs used to treat dementia. Various experimental techniques were used to evaluate the effect of Mat on these two targets both in vitro and in AD mouse model. Mat could inhibit Aβ42-induced cytotoxicity and suppress the Aβ/RAGE signaling pathway in vitro. Additionally, the results of in vivo evaluations of the effects of Mat on the two targets were consistent with the results of our in vitro studies. Furthermore, Mat reduced proinflammatory cytokines and Aβ deposition and attenuated the memory deficits of AD transgenic mice. We believe that this novel, multi-target strategy to inhibit both Aβ and RAGE, is worthy of further exploration. Therefore, our future studies will focus on identifying even more effective multi-target compounds for the treatment of AD based on the molecular structure of Mat.
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China. lilicui_gmu@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Wanwen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Liu
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.|Institutes of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Jianghao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Departments of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cao
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.|Institutes of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Tao
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Mingkang
authors.initials: M
authors.lastname: Yin
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Pengru
authors.initials: P
authors.lastname: Huang
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China. lilicui_gmu@163.com.|Institute of clinical medicine, Jinan University, Guangzhou, People's Republic of China. lilicui_gmu@163.com.
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
authors.affiliation: Guangdong key laboratory of age-related cardiac and cerebral diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China. binzhao0759@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D060825:Cognitive Dysfunction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011807:Quinolizines / Q000008:administration & dosage*; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000093842:Matrines
chemical_list: C000593873:Ager protein, mouse; D000470:Alkaloids; D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D010446:Peptide Fragments; D011807:Quinolizines; D000067759:Receptor for Advanced Glycation End Products; C075222:amyloid beta-protein (1-42); D000093842:Matrines
keywords: Alzheimer’s disease; Matrine; Receptors for Advanced glycation end product; β-Amyloid peptide