title: Protective effects of a Chotosan Fraction and its active components on β-amyloid-induced neurotoxicity.
abstract: Chotosan (CTS) is a traditional Kampo prescription used to treat chronic headache and hypertension. Recent clinical studies demonstrated that CTS has ameliorative effects on dementia. This study aims to identify the anti-Alzheimer components in CTS. β-amyloid (Aβ) is considered to play a central role in the pathophysiology of Alzheimer's disease. CTS-E, a fraction of CTS, showed significant protective effects on Aβ-induced neurotoxicity. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used for the qualitative analysis of it. Among the identified constituents, neuroprotective effects against Aβ(25-35)-induced neurotoxicity of 10 major compounds were tested by MTT assay. Their inhibitory action on Aβ(1-42) self-induced aggregation was measured by Thioflavin T-binding assay. The results showed that caffeic acid, chlorogenic acid, 1,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid had significant neuroprotective effects on Aβ(25-35)-induced neurotoxicity. Besides these phenolic acids, nobiletin and hesperidin could also inhibit Aβ(1-42) self-induced aggregation. In conclusion, the neuroprotective fraction, CTS-E, could protect PC12 cells from Aβ-induced neurotoxicity. Anti-oxidative effects may at least partly mediate the neuroprotective effects of it. Phenolic acids from Chrysanthemi Flos and flavonoids from Citri Reticulatae Pericarpium might be the effective constituents in CTS-E.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Menglin
authors.initials: M
authors.lastname: Wei
authors.affiliation: Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Jiazhuo
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: liuwenyuan@cpu.edu.cn.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China. Electronic address: fengfeng@cpu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D016923:Cell Death; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D066329:Protein Aggregates; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D010446:Peptide Fragments; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); C120250:choto-san
keywords: Alzheimer’s disease; Caffeoylquinic acids; Chotosan; Quadrupole time-of-flight mass spectrometry; β-Amyloid