title: The Protective Effects of Icariin against the Homocysteine-Induced Neurotoxicity in the Primary Embryonic Cultures of Rat Cortical Neurons.
abstract: Icariin, an ingredient in the medicinal herbEpimedium brevicornumMaxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this study we aim to investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity in primary embryonic cultures of rat cortical neurons. Our findings demonstrated that icariin might be able restore the cytoskeleton network damaged by Hcy through the modulation of acetyl-α-tubulin, tyrosinated-α-tubulin, and phosphorylation of the tubulin-binding protein Tau. In addition, icariin downregulated p-extracellular signal-regulated kinase (ERK) which is a kinase targeting tau protein. Furthermore, icariin effectively restored the neuroprotective protein p-Akt that was downregulated by Hcy. We also applied RT² Profiler PCR Arrays focused on genes related to AD and neurotoxicity to examine genes differentially altered by Hcy or icariin. Among the altered genes from the arrays, ADAM9 was downregulated 15 folds in cells treated with Hcy, but markedly restored by icariin. ADAM family, encoded α-secreatase, plays a protective role in AD. Overall, our findings demonstrated that icariin exhibits a strong neuroprotective function and have potential for future development for drug treating neurological disorders, such as AD.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Av. Wai Long, Taipa, Macau, China. 1309853pct20001@student.must.edu.mo.
authors.forename: Xiao-Ang
authors.initials: XA
authors.lastname: Li
authors.affiliation: School of Nursing, The Hong Kong Polytechnic University, Kowloon, Hong Kong, China. janice.ys.ho@polyu.edu.hk.
authors.forename: Yuen-Shan
authors.initials: YS
authors.lastname: Ho
authors.affiliation: Department of Genetics, Rutgers University, New Brunswick, NJ 07001, USA. larichen7@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Av. Wai Long, Taipa, Macau, China. wlhsiao@must.edu.mo.
authors.forename: W L Wendy
authors.initials: WL
authors.lastname: Hsiao
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology*; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006710:Homocysteine / Q000009:adverse effects*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; D006710:Homocysteine; D051722:ADAM Proteins; C503705:Adam9 protein, rat; C056599:icariin
keywords: RT2 Profiler PCR array; homocysteine; icariin; neuroprotection