title: Icariin protects SH-SY5Y cells from formaldehyde-induced injury through suppression of Tau phosphorylation.
abstract: OBJECTIVE
  To investigate the neuroprotective effects of icariin on formaldehyde (FA)-treated human neuroblastoma SH-SY5Y cells and the possible mechanisms involved.
  
  
  METHODS
  SH-SY5Y cells were divided into FA treatment group, FA treatment group with icariin, and the control group. Cell viability, apoptosis, and morphological changes were determined by cell counting kit-8 (CCK 8), flow cytometry, and confocal microscopy, respectively. The phosphorylation of Tau protein was examined by western blotting.
  
  
  RESULTS
  FA showed a half lethal dose (LD50) of 0.3 mmol/L in SH-SY5Y cells under the experimental conditions. Icariin (1-10 µmol/L) prevented FA-induced cell death in SH-SY5Y cells in a dose-dependent manner, with the optimal effect observed at 5 µmol/L. After FA treatment, the absorbance in FA group was 1.31±0.05, while in the group of icariin (5 µmol/L) was 1.63±0.05. Examination of cell morphology by confocal microscopy demonstrated that 5 µmol/L icariin significantly attenuated FA-induced cell injury (P <0.05). Additionally, Icariin inhibited FA-induced cell apoptosis in SH-SY5Y cells. Results from western blotting showed that icariin suppressed FA-induced phosphorylation at Thr 181 and Ser 396 of Tau protein, while having no effect on the expression of the total Tau protein level. Furthermore, FA activated Tau kinase glycogen synthase kinase 3 beta (GSK-3β) by enhancement of Y216 phosphorylation, but icariin reduced Y216 phosphorylation and increased Ser 9 phosphorylation.
  
  
  CONCLUSIONS
  Icariin protects SH-SY5Y cells from FA-induced injury poßsibly through the inhibition of GSK-3β-mediated Tau phosphorylation.
authors.affiliation: Integrated Laboratory of Chinese and Western Medicine, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Yi-Xiang
authors.initials: YX
authors.lastname: Song
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Jun-Ye
authors.initials: JY
authors.lastname: Miao
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Min
authors.initials: M
authors.lastname: Qiang
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Rong-Qiao
authors.initials: RQ
authors.lastname: He
authors.affiliation: Integrated Laboratory of Chinese and Western Medicine, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Integrated Laboratory of Chinese and Western Medicine, Peking University First Hospital, Beijing, 100034, China. weiwei_ivy@163.com.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005557:Formaldehyde; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; D016875:tau Proteins; D005557:Formaldehyde; D000071679:Glycogen Synthase Kinase 3 beta; C056599:icariin
keywords: Tau phosphorylation; formaldehyde; glycogen synthase kinase 3 beta; icariin; neuroprotection