Memory enhancing actions of Asiasari radix extracts via activation of insulin receptor and extracellular signal regulated kinase (ERK) I/II in rat hippocampus.
Brain insulin receptor and ERK I/II are suggested to play a role in memory formation. We designed a series of experiments to explore if Asiasari radix (AR) extracts could display memory enhancing actions possibly via the activation of insulin receptor and ERK I/II in mice and rats. Methanol extract of AR had significantly increased survival time in the NaNO(2) intoxication assay in mice. Methanol extract of Asiasari radix (fraction 1) and its subfractions, chloroform-soluble fraction (fraction 2) and chloroform-insoluble, methanol-soluble fraction (fraction 4) were further tested for memory formation. In eight-arm radial maze experiments, both reference memory errors and working memory errors were significantly decreased in mice by fractions 1, 2 and 4. In addition, these fractions were also effective in promoting memory in the passive avoidance test in mice and rats. To gain insight into the mechanism of memory enhancing effects by Asiasari radix extracts, the activities of hippocampal insulin receptors and ERK I/II were tested in mice and rats. Fraction 1 significantly stimulated tyrosine phosphorylation of the insulin receptor, whereas ERK I/II were stimulated by fractions 1, 2 and 4. These fractions also inhibited cholinesterase activities in rats. These results suggest that Asiasari radix extracts may exert memory enhancing effects via activation of insulin receptor and ERK I/II as well as decreasing cholinesterase activity.
Department of Pharmacology, School of Dentistry, Kyung Hee University, Seoul 130-701, South Korea.
Yong
Y
Han
Sung-Jin
SJ
Kim
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D030023:Asarum / Q000737:chemistry*; D001362:Avoidance Learning / Q000187:drug effects; D015153:Blotting, Western; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007928:Lethal Dose 50; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D020258:Neurotoxicity Syndromes / Q000523:psychology; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology / Q000633:toxicity; D011233:Precipitin Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000187:drug effects*; D012977:Sodium Nitrite / Q000633:toxicity; D014443:Tyrosine / Q000378:metabolism
D010936:Plant Extracts; D014443:Tyrosine; D011972:Receptor, Insulin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000110:Acetylcholinesterase; D012977:Sodium Nitrite