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Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β

BACKGROUND AND AIM: The aging-dependent activation of glycogen synthase kinase-3β (GSK-3β) has been suggested to be important in the onset of dementia. To discover novel therapeutic Kampo medicines for dementia, we examined the effects of orengedokuto (OGT; 黃連解毒湯 huáng lián jiědú tāng) and san'...

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Autores principales: Fujiwara, Hironori, Yoshida, Jun, Dibwe, Dya Fita, Awale, Suresh, Hoshino, Haruka, Kohama, Hiroshi, Arai, Hiroyuki, Kudo, Yukitsuka, Matsumoto, Kinzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702137/
https://www.ncbi.nlm.nih.gov/pubmed/31453129
http://dx.doi.org/10.1016/j.jtcme.2018.12.001
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author Fujiwara, Hironori
Yoshida, Jun
Dibwe, Dya Fita
Awale, Suresh
Hoshino, Haruka
Kohama, Hiroshi
Arai, Hiroyuki
Kudo, Yukitsuka
Matsumoto, Kinzo
author_facet Fujiwara, Hironori
Yoshida, Jun
Dibwe, Dya Fita
Awale, Suresh
Hoshino, Haruka
Kohama, Hiroshi
Arai, Hiroyuki
Kudo, Yukitsuka
Matsumoto, Kinzo
author_sort Fujiwara, Hironori
collection PubMed
description BACKGROUND AND AIM: The aging-dependent activation of glycogen synthase kinase-3β (GSK-3β) has been suggested to be important in the onset of dementia. To discover novel therapeutic Kampo medicines for dementia, we examined the effects of orengedokuto (OGT; 黃連解毒湯 huáng lián jiědú tāng) and san'oshashinto (SST; 三黃瀉心湯 sān huáng xiè xīn tāng) on memory deficits and GSK-3β activity in senescence-accelerated prone mice (SAMP8). EXPERIMENTAL PROCEDURE: The object recognition test (ORT) and conditioned fear memory test (CFT) were employed to elucidate short-term working memory and long-term fear memory. The activity of GSK-3β and the phosphorylation of related molecules were measured using a kinase assay and Western blotting. RESULTS AND CONCLUSION: OGT and SST attenuated memory deficits in SAMP8 in ORT, but not in CFT. In ex vivo experiments, cortical GSK-3β activity was significantly stronger in SAMP8 than in SAMR1. The enhanced cortical GSK-3β activity in SAMP8 was accompanied by a significant increase in the level of phosphorylated collapsin response mediator protein-2 (CRMP2), an important factor that is involved in the regulation of microtubule stability. OGT and SST attenuated not only increases in cortical GSK-3β activity, but also the levels of phosphorylated CRMP2 in SAMP8. In vitro experiments, flavonoids contained in these kampo medicines, inhibited GSK-3β activity in concentration-dependent manners. These results suggest that OGT and SST prevent aging-induced short-term working memory deficits by inhibiting aging-dependent elevations in the cortical GSK-3β activity and subsequent CRMP2 phosphorylation.
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spelling pubmed-67021372019-08-26 Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β Fujiwara, Hironori Yoshida, Jun Dibwe, Dya Fita Awale, Suresh Hoshino, Haruka Kohama, Hiroshi Arai, Hiroyuki Kudo, Yukitsuka Matsumoto, Kinzo J Tradit Complement Med Original article BACKGROUND AND AIM: The aging-dependent activation of glycogen synthase kinase-3β (GSK-3β) has been suggested to be important in the onset of dementia. To discover novel therapeutic Kampo medicines for dementia, we examined the effects of orengedokuto (OGT; 黃連解毒湯 huáng lián jiědú tāng) and san'oshashinto (SST; 三黃瀉心湯 sān huáng xiè xīn tāng) on memory deficits and GSK-3β activity in senescence-accelerated prone mice (SAMP8). EXPERIMENTAL PROCEDURE: The object recognition test (ORT) and conditioned fear memory test (CFT) were employed to elucidate short-term working memory and long-term fear memory. The activity of GSK-3β and the phosphorylation of related molecules were measured using a kinase assay and Western blotting. RESULTS AND CONCLUSION: OGT and SST attenuated memory deficits in SAMP8 in ORT, but not in CFT. In ex vivo experiments, cortical GSK-3β activity was significantly stronger in SAMP8 than in SAMR1. The enhanced cortical GSK-3β activity in SAMP8 was accompanied by a significant increase in the level of phosphorylated collapsin response mediator protein-2 (CRMP2), an important factor that is involved in the regulation of microtubule stability. OGT and SST attenuated not only increases in cortical GSK-3β activity, but also the levels of phosphorylated CRMP2 in SAMP8. In vitro experiments, flavonoids contained in these kampo medicines, inhibited GSK-3β activity in concentration-dependent manners. These results suggest that OGT and SST prevent aging-induced short-term working memory deficits by inhibiting aging-dependent elevations in the cortical GSK-3β activity and subsequent CRMP2 phosphorylation. Elsevier 2018-12-27 /pmc/articles/PMC6702137/ /pubmed/31453129 http://dx.doi.org/10.1016/j.jtcme.2018.12.001 Text en © 2019 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Fujiwara, Hironori
Yoshida, Jun
Dibwe, Dya Fita
Awale, Suresh
Hoshino, Haruka
Kohama, Hiroshi
Arai, Hiroyuki
Kudo, Yukitsuka
Matsumoto, Kinzo
Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β
title Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β
title_full Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β
title_fullStr Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β
title_full_unstemmed Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β
title_short Orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β
title_sort orengedokuto and san'oshashinto improve memory deficits by inhibiting aging-dependent activation of glycogen synthase kinase-3β
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702137/
https://www.ncbi.nlm.nih.gov/pubmed/31453129
http://dx.doi.org/10.1016/j.jtcme.2018.12.001
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