title: The neuroprotective effects and possible mechanism of action of a methanol extract from Asparagus cochinchinensis: In vitro and in vivo studies.
abstract: Extracts of Asparagus cochinchinensis (AC) have antitumor, anti-inflammatory, and immunostimulant effects. The neurobiological mechanisms underlying the effects of AC have not been sufficiently explored. Thus we performed in vivo and in vitro experiments to further characterize potential therapeutic effects and to clarify the underlying mechanisms. In the tail suspension test immobility time was significantly reduced after administration of AC which suggests antidepressant-like activity without effect on body core temperature. Moreover, in animals pretreated with AC infarct size after occlusion of the middle cerebral artery was reduced. In vitro experiments confirmed neuroprotective effects. Total saponin obtained from AC significantly inhibited H2O2-induced cell death in cultured cortical neurons. The survival-promoting effect by AC saponins 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, phosphorylation of Scr homology-2 (SH2) domain-containing phosphatase 2 (Shp-2) was induced by AC, and the protective effect of AC was abolished by NSC87877, an inhibitor for Shp-2, suggesting an involvement of Shp-2 mediated intracellular signaling in AC saponins. Moreover, AC-induced activation of pShp-2 and ErK1/2 were blocked by NSC87877 indicating that activation of these signaling pathways was mediated by the Shp-2 signaling pathway. These effects appear to be associated with activation of the Shp-2, ErK1/2 and Akt signaling pathways. Our results suggest that AC has antidepressant-like and neuroprotective (reducing infarct size) effects and that activation of pShp-2 and pErK1/2 pathways may be involved in the effects.
authors.affiliation: Institute of Traditional Medicine and Technology, Ministry of Education, Culture, and Science, Ulaanbaatar, Mongolia; Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Jalsrai
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Numakawa
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kunugi
authors.affiliation: Otto von Guericke University, Faculty of Medicine, Institute of Pharmacology and Toxicology, Leipziger Strasse 44, 39120 Magdeburg, Germany; CBBS, Center for Behavioral Brain Siences, Magdeburg, Germany.
authors.forename: D C
authors.initials: DC
authors.lastname: Dieterich
authors.affiliation: Otto von Guericke University, Faculty of Medicine, Institute of Pharmacology and Toxicology, Leipziger Strasse 44, 39120 Magdeburg, Germany. Electronic address: axel.becker@med.ovgu.de.
authors.forename: A
authors.initials: A
authors.lastname: Becker
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D027761:Asparagus Plant / Q000737:chemistry; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003866:Depressive Disorder / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D000432:Methanol / Q000737:chemistry; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D018696:Neuroprotective Agents; D010936:Plant Extracts; D012503:Saponins; D000432:Methanol
keywords: Asparagus cochinchinensis; ErK/Shp-2; neuroprotection; saponin