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05 24, 2021;11 (1): 10790.

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

Yi-An Lin, Yan-Rong Li, Yi-Ching Chang, Mei-Chich Hsu, Szu-Tah Chen
Author Information
  1. Yi-An Lin: Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
  2. Yan-Rong Li: Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan.
  3. Yi-Ching Chang: Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan.
  4. Mei-Chich Hsu: Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan. meichich@gmail.com.
  5. Szu-Tah Chen: Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan. stc1105@cgmh.org.tw.
PMID: 34031457 DOI: 10.1038/s41598-021-89039-0

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.

References

  1. J Agric Food Chem. 2018 May 9;66(18):4734-4740 [PMID: 29685038]
  2. Biochem Biophys Res Commun. 2010 Oct 1;400(4):679-83 [PMID: 20816664]
  3. J Agric Food Chem. 2020 Feb 5;68(5):1306-1314 [PMID: 31957433]
  4. Mol Cell Endocrinol. 2008 Sep 24;292(1-2):11-9 [PMID: 18588941]
  5. Molecules. 2017 Jun 13;22(6): [PMID: 28608833]
  6. Mar Drugs. 2020 May 19;18(5): [PMID: 32438641]
  7. Am J Physiol Cell Physiol. 2012 Sep 1;303(5):C475-85 [PMID: 22700795]
  8. J Endocrinol. 2017 Aug;234(2):187-200 [PMID: 28533420]
  9. Bone. 2015 Nov;80:115-125 [PMID: 26453501]
  10. Biogerontology. 2016 Jun;17(3):619-39 [PMID: 26538344]
  11. J Strength Cond Res. 2014 Aug;28(8):2338-45 [PMID: 24531430]
  12. Exerc Immunol Rev. 2015;21:8-25 [PMID: 25826432]
  13. PLoS One. 2018 Nov 15;13(11):e0207533 [PMID: 30440034]
  14. Am J Physiol Cell Physiol. 2009 Jun;296(6):C1248-57 [PMID: 19357234]
  15. Sci Rep. 2016 Feb 02;6:20300 [PMID: 26831566]
  16. J Chromatogr A. 2007 Sep 7;1163(1-2):96-104 [PMID: 17606269]
  17. Biomed Pharmacother. 2016 Oct;83:1089-1094 [PMID: 27551754]
  18. FEBS J. 2013 Sep;280(17):4294-314 [PMID: 23517348]
  19. Biochem Biophys Res Commun. 2015 Aug 21;464(2):596-602 [PMID: 26151859]
  20. Biochim Biophys Acta. 2013 Sep;1832(9):1410-20 [PMID: 23523469]
  21. Nat Commun. 2016 Aug 03;7:12397 [PMID: 27484840]
  22. Appl Physiol Nutr Metab. 2009 Oct;34(5):817-28 [PMID: 19935843]
  23. Skelet Muscle. 2011 Jan 24;1(1):4 [PMID: 21798082]
  24. Nutr Res Rev. 2013 Dec;26(2):149-65 [PMID: 23930668]
  25. Biochem Biophys Res Commun. 2004 Nov 19;324(3):986-92 [PMID: 15485651]
  26. Endocrinology. 2011 Jan;152(1):193-206 [PMID: 21084444]
  27. Phytomedicine. 2021 Feb;82:153413 [PMID: 33339654]
  28. Skelet Muscle. 2011 Sep 08;1:29 [PMID: 21902831]
  29. PLoS One. 2018 Oct 24;13(10):e0206146 [PMID: 30356272]
  30. Biomed Pharmacother. 2019 Jul;115:108930 [PMID: 31055234]
  31. Mol Cell. 2004 May 7;14(3):395-403 [PMID: 15125842]
  32. Eur J Pharmacol. 2016 Sep 5;786:53-59 [PMID: 27238975]
  33. Int J Exp Pathol. 2012 Jun;93(3):157-71 [PMID: 22564195]
  34. J Appl Physiol (1985). 2004 Jan;96(1):203-10 [PMID: 12959952]
  35. Endocrinology. 2012 Jan;153(1):241-53 [PMID: 22087027]
  36. Cell Mol Life Sci. 2013 Nov;70(21):4117-30 [PMID: 23552962]
  37. BMC Complement Altern Med. 2014 May 03;14:144 [PMID: 24884709]
  38. Int J Biochem Cell Biol. 2005 Oct;37(10):1974-84 [PMID: 16087388]
  39. Eur J Pharmacol. 2015 Jul 5;758:60-3 [PMID: 25840280]
  40. Molecules. 2014 Jul 03;19(7):9502-14 [PMID: 24995929]
  41. Cell Mol Life Sci. 2014 Nov;71(22):4361-71 [PMID: 25080109]
  42. J Cell Biochem. 2009 Oct 1;108(2):458-68 [PMID: 19639604]
  43. Am J Physiol Endocrinol Metab. 2006 Jul;291(1):E80-9 [PMID: 16760336]
  44. Biochem Biophys Res Commun. 2018 Sep 10;503(3):1409-1414 [PMID: 30025893]
  45. Transplantation. 2014 Jul 27;98(2):139-47 [PMID: 24926828]
  46. Exp Mol Med. 2017 Sep 15;49(9):e377 [PMID: 28912572]
  47. Asian J Androl. 2006 Sep;8(5):601-5 [PMID: 16751992]
  48. Cell Biol Int. 2007 Oct;31(10):1274-9 [PMID: 17590360]
  49. Stress. 2010 Mar;13(2):132-41 [PMID: 19929313]
  50. Mol Cells. 2009 Nov 30;28(5):495-9 [PMID: 19855934]
  51. Andrologia. 2018 Feb;50(1): [PMID: 28294371]
  52. Med Sci Sports Exerc. 2012 Apr;44(4):610-5 [PMID: 21946153]
  53. J Cell Biol. 2009 Dec 14;187(6):859-74 [PMID: 20008564]
  54. J Ethnopharmacol. 2011 Apr 12;134(3):519-41 [PMID: 21215308]
  55. FASEB J. 2018 Apr;32(4):1741-1777 [PMID: 29242278]
  56. Clin Exp Dermatol. 2017 Apr;42(3):287-294 [PMID: 28211089]
  57. J Muscle Res Cell Motil. 2012 Mar;32(6):383-90 [PMID: 22012579]
  58. Nat Rev Drug Discov. 2015 Jan;14(1):58-74 [PMID: 25549588]
  59. Evid Based Complement Alternat Med. 2015;2015:235265 [PMID: 25705234]
  60. J Nutr Biochem. 2018 Nov;61:155-162 [PMID: 30236872]
  61. Biochem Biophys Res Commun. 2007 Sep 14;361(1):237-42 [PMID: 17658471]
  62. Food Funct. 2019 Jan 22;10(1):259-265 [PMID: 30560247]
  63. Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E591-601 [PMID: 15100091]
  64. Life Sci. 2015 Apr 1;126:57-68 [PMID: 25634110]

MeSH Term

Animals
Cell Differentiation
Cell Line
Chromones
Flavonoids
Gene Expression Regulation
Hypertrophy
Insulin-Like Growth Factor I
Mice
Morpholines
Myoblasts
Myosin Heavy Chains
Podophyllotoxin
Signal Transduction
Sirolimus

Chemicals

Chromones
Flavonoids
Morpholines
insulin-like growth factor-1, mouse
picropodophyllin
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Insulin-Like Growth Factor I
Myosin Heavy Chains
Podophyllotoxin
icariin
Sirolimus
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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