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(-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation
In this study, for the purpose of elucidation for antidiabetic components, we isolated and identified compounds that could become lead compounds for the development of antidiabetic agents from the herbal medicine Vitex trifolia, which is used for liver protection in Myanmar. Three kinds of lignan, (...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994966/ https://www.ncbi.nlm.nih.gov/pubmed/31878261 http://dx.doi.org/10.3390/molecules25010073 |
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author | Ukiya, Motohiko Sato, Daisuke Kimura, Hirokazu Koketsu, Mamoru Phay, Nyunt Nishina, Atsuyoshi |
author_facet | Ukiya, Motohiko Sato, Daisuke Kimura, Hirokazu Koketsu, Mamoru Phay, Nyunt Nishina, Atsuyoshi |
author_sort | Ukiya, Motohiko |
collection | PubMed |
description | In this study, for the purpose of elucidation for antidiabetic components, we isolated and identified compounds that could become lead compounds for the development of antidiabetic agents from the herbal medicine Vitex trifolia, which is used for liver protection in Myanmar. Three kinds of lignan, (-)-O-methylcubebin (MC), (-)-hinokinin, and (-)-cubebin, were isolated from the ethyl acetate extract of the leaves of V. trifolia, using various chromatography. Among the three isolated compounds, MC showed the strongest effects to increase intracellular lipid accumulation in 3T3-L1 cells. From the results of the elucidation of the MC’s effects on the adipogenesis of 3T3-L1 cells, the downsizing of adipocytes and the promotion of the expression of adipogenesis-related proteins, as well as adiponectin, were observed. On the other hand, since the activity of MC was inhibited by antagonists of PPARγ and improved by inhibitors of the classical mitogen-activated protein kinase (MAPK) pathway and p38MAPK pathway, MC was considered to be an agonist of PPARγ, and furthermore promoted adipogenesis via the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK phosphorylation. Although MC showed similar effects to those of rosiglitazone (RO) used as a positive control, RO promoted the migration of GLUT4 from the cytoplasm to the cell membrane, whereas MC did not show such an effect. From the abovementioned results, it was considered that MC could be a lead compound for the development of antidiabetic drugs that does not show weight gain, which is a side effect of RO. |
format | Online Article Text |
id | pubmed-6994966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69949662020-02-13 (-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation Ukiya, Motohiko Sato, Daisuke Kimura, Hirokazu Koketsu, Mamoru Phay, Nyunt Nishina, Atsuyoshi Molecules Article In this study, for the purpose of elucidation for antidiabetic components, we isolated and identified compounds that could become lead compounds for the development of antidiabetic agents from the herbal medicine Vitex trifolia, which is used for liver protection in Myanmar. Three kinds of lignan, (-)-O-methylcubebin (MC), (-)-hinokinin, and (-)-cubebin, were isolated from the ethyl acetate extract of the leaves of V. trifolia, using various chromatography. Among the three isolated compounds, MC showed the strongest effects to increase intracellular lipid accumulation in 3T3-L1 cells. From the results of the elucidation of the MC’s effects on the adipogenesis of 3T3-L1 cells, the downsizing of adipocytes and the promotion of the expression of adipogenesis-related proteins, as well as adiponectin, were observed. On the other hand, since the activity of MC was inhibited by antagonists of PPARγ and improved by inhibitors of the classical mitogen-activated protein kinase (MAPK) pathway and p38MAPK pathway, MC was considered to be an agonist of PPARγ, and furthermore promoted adipogenesis via the inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38MAPK phosphorylation. Although MC showed similar effects to those of rosiglitazone (RO) used as a positive control, RO promoted the migration of GLUT4 from the cytoplasm to the cell membrane, whereas MC did not show such an effect. From the abovementioned results, it was considered that MC could be a lead compound for the development of antidiabetic drugs that does not show weight gain, which is a side effect of RO. MDPI 2019-12-24 /pmc/articles/PMC6994966/ /pubmed/31878261 http://dx.doi.org/10.3390/molecules25010073 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ukiya, Motohiko Sato, Daisuke Kimura, Hirokazu Koketsu, Mamoru Phay, Nyunt Nishina, Atsuyoshi (-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation |
title | (-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation |
title_full | (-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation |
title_fullStr | (-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation |
title_full_unstemmed | (-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation |
title_short | (-)-O-Methylcubebin from Vitex trifolia Enhanced Adipogenesis in 3T3-L1 Cells via the Inhibition of ERK1/2 and p38MAPK Phosphorylation |
title_sort | (-)-o-methylcubebin from vitex trifolia enhanced adipogenesis in 3t3-l1 cells via the inhibition of erk1/2 and p38mapk phosphorylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994966/ https://www.ncbi.nlm.nih.gov/pubmed/31878261 http://dx.doi.org/10.3390/molecules25010073 |
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