Inhibition of β-amyloid Aggregation By Albiflorin, Aloeemodin And Neohesperidin And Their Neuroprotective Effect On Primary Hippocampal Cells Against β-amyloid Induced Toxicity.
Being one of the hallmarks of Alzheimer's disease, β-amyloid (Aβ) aggregates induce complicated neurotoxicity. Evidences show that the underlying mechanism of neurotoxicity involves a glutamate receptor subtype, N-methyl-D-aspartate (NMDA) receptor, an increase in intracellular calcium(II) ion loading as well as an elevation in oxidation stress. In this work, among the 35 chemical components of Chinese herbal medicines (CHMs) being screened for inhibitors of Aβ aggregation, four of them, namely albiflorin, aloeemodin, neohesperidin and physcion, were found for the first time to exhibit a potent inhibitory effect on Aβ(1-40) and Aβ(1-42) aggregation. Their neuroprotective capability on primary hippocampal neuronal cells was also investigated by MTT assay, ROS assay and intracellular calcium(II) ion concentration measurement. It was interesting to find that physcion was rather toxic to neuronal cells while albiflorin, aloeemodin and neohesperidin reduced the toxicity and ROS induced by both monomeric and oligomeric Aβ species. In addition, albiflorin was particularly powerful in maintaining the intracellular Ca(2+) concentration.
See-Lok
SL
Ho
Chung-Yan
CY
Poon
Chengyuan
C
Lin
Ting
T
Yan
Daniel Wai-Jing
DW
Kwong
Ken Kin-Lam
KK
Yung
Man S
MS
Wong
Zhaoxiang
Z
Bian
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, P.R. China. hwli@hkbu.edu.hk.
Hung-Wing
HW
Li
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001952:Bridged-Ring Compounds / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004642:Emodin / Q000031:analogs & derivatives / Q000737:chemistry; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D007477:Ions / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D066329:Protein Aggregates / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D006027:Glycosides
D016229:Amyloid beta-Peptides; D001952:Bridged-Ring Compounds; D002118:Calcium; D004642:Emodin; D006569:Hesperidin; D007477:Ions; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C014959:albiflorin; D006027:Glycosides; C546526:neohesperidin