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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'...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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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. |
format | Online Article Text |
id | pubmed-6702137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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