Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy

Abstract The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as repr...

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Autores principales:	Yi-An Lin, Yan-Rong Li, Yi-Ching Chang, Mei-Chich Hsu, Szu-Tah Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/370a7efabb5a44bbabf65ba11eba80c9
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spelling	oai:doaj.org-article:370a7efabb5a44bbabf65ba11eba80c92021-12-02T15:49:35ZActivation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy10.1038/s41598-021-89039-02045-2322https://doaj.org/article/370a7efabb5a44bbabf65ba11eba80c92021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89039-0https://doaj.org/toc/2045-2322Abstract The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.Yi-An LinYan-Rong LiYi-Ching ChangMei-Chich HsuSzu-Tah ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yi-An Lin Yan-Rong Li Yi-Ching Chang Mei-Chich Hsu Szu-Tah Chen Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy
description	Abstract The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways. C2C12 myotube hypertrophy was demonstrated by enlarged myotube and increased myosin heavy chains (MyHCs). In similar to IGF-1, EE/ICA activated key components of the IGF-1 signal pathway, including IGF-1 receptor. Pre-treatment with IGF-1 signal pathway specific inhibitors such as picropodophyllin, LY294002, and rapamycin attenuated EE induced myotube hypertrophy and MyHC isoform overexpression. In a different way, EE induced MHyC-S overexpression can be blocked by AMPK, but not by mTOR inhibitor. On the level of transcription, EE suppressed myostatin and MRF4 expression, but did not suppress atrogenes MAFbx and MuRF1 like IGF-1 did. Differential regulation of MyHC isoform and atrogenes is probably due to inequivalent AKT and AMPK phosphorylation induced by EE and IGF-1. These findings suggest that EE/ICA stimulates pathways partially overlapping with IGF-1 signaling pathway to promote myotube hypertrophy.
format	article
author	Yi-An Lin Yan-Rong Li Yi-Ching Chang Mei-Chich Hsu Szu-Tah Chen
author_facet	Yi-An Lin Yan-Rong Li Yi-Ching Chang Mei-Chich Hsu Szu-Tah Chen
author_sort	Yi-An Lin
title	Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy
title_short	Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy
title_full	Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy
title_fullStr	Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy
title_full_unstemmed	Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy
title_sort	activation of igf-1 pathway and suppression of atrophy related genes are involved in epimedium extract (icariin) promoted c2c12 myotube hypertrophy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/370a7efabb5a44bbabf65ba11eba80c9
work_keys_str_mv	AT yianlin activationofigf1pathwayandsuppressionofatrophyrelatedgenesareinvolvedinepimediumextracticariinpromotedc2c12myotubehypertrophy AT yanrongli activationofigf1pathwayandsuppressionofatrophyrelatedgenesareinvolvedinepimediumextracticariinpromotedc2c12myotubehypertrophy AT yichingchang activationofigf1pathwayandsuppressionofatrophyrelatedgenesareinvolvedinepimediumextracticariinpromotedc2c12myotubehypertrophy AT meichichhsu activationofigf1pathwayandsuppressionofatrophyrelatedgenesareinvolvedinepimediumextracticariinpromotedc2c12myotubehypertrophy AT szutahchen activationofigf1pathwayandsuppressionofatrophyrelatedgenesareinvolvedinepimediumextracticariinpromotedc2c12myotubehypertrophy
_version_	1718385682943049728

Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy

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