Phosphatase-mediated intracellular signaling contributes to neuroprotection by flavonoids of Iris tenuifolia.
A variety of flavonoids are suggested to be useful for the treatment of brain-related disorders, including dementia and depression. An investigation on the characteristics of the extracted compounds of Iris tenuifolia Pall. (IT) is of much interest, as this plant has been used as a traditional medicine. In the present study, we examined the effect of total flavonoids obtained from IT on cultured cortical neurons under oxidative-stress and found that pretreatment with IT flavonoids significantly inhibited H 2 O 2-induced cell death in cortical neurons. Such a survival-promoting effect by IT flavonoids was partially blocked by inhibitors for extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase/Akt (PI3K/Akt) cascades, both of which are known as survival-promoting signaling molecules. Furthermore, the phosphorylation of Src homology-2 (SH2) domain-containing phosphatase2 (Shp2) was induced by IT flavonoids, and the protective effect of IT flavonoids was abolished by NSC87877, an inhibitor for Shp2, suggesting the involvement of Shp2-mediated intracellular signaling in flavonoid-dependent neuroprotection.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Aldarmaa
A
Jalsrai
Tadahiro
T
Numakawa
Yoshiko
Y
Ooshima
Naoki
N
Adachi
Hiroshi
H
Kunugi
D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000009:adverse effects; D031323:Iris Plant / Q000737:chemistry*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D005419:Flavonoids; D018696:Neuroprotective Agents; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11