DOI QR코드

DOI QR Code

The Effects of Astragali Radix Extracts on Mitochondrial Function in C2C12 Myotubes

C2C12 골격근세포에서 황기의 미토콘드리아 조절 작용

  • Song, Miyoung (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dongguk University)
  • 송미영 (동국대학교 한의과대학 한방재활의학교실)
  • Received : 2014.11.17
  • Accepted : 2014.12.05
  • Published : 2014.12.30

Abstract

Objective: The prevalence of metabolic syndrome and type 2 diabetes is increasing worldwide. Mitochondrial dysfunction is known to be involved in insulin resistance and obesity, researches have been increasing highly. Astragali Radix extract (ARE) or its main components have been shown to perform comparably to insulin by significantly reducing blood glucose levels in animal models however, the influence on mitochondrial dysfunction are not well understood. Methods: ARE (0.2, 0.5 and 1.0 mg/ml) or metformin (2.5 mM) were treated in C2C12 after 6 day-differentiation. The expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and phosphorylation AMPK, peroxisome proliferators-activated receptror ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$), nuclear respiratory factors 1 (NRF1), mitochondrial transcription factor (Tfam) and myosin heavy chain were detected with western blotting or polymerase chain reaction analysis. The morphological changes were also investigated. Results: ARE dose dependently increased phosphorylation of AMPK and respectively activated mRNA expressions of $PGC1{\alpha}$, NRF1 and Tfam which are mitochondrial biogenesis regulators. Furthermore, there were some morphologic differences of differentiated cells between ARE treatment and control. Conclusions: This study suggests that ARE has the potential to increase muscle mitochondrial function by activating AMPK and $PGC1{\alpha}$.

Keywords

References

  1. Wallace DC. A mitochondrial bioenergetic etiology of disease. J Clin Invest. 2013 ; 123(4) : 1405-12. https://doi.org/10.1172/JCI61398
  2. Lee HK, Cho YM, Kwak SH, Lim S, Park KS, Shim EB. Mitochondrial dysfunction and metabolic syndrome-looking for environmental factors. Biochimica et Biophysica Acta. 2010 ; 1800(3) ; 282-9. https://doi.org/10.1016/j.bbagen.2009.11.010
  3. Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science. 2005 ; 307(5708) : 384-7. https://doi.org/10.1126/science.1104343
  4. Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. 2008 ; 102(4) : 401-14. https://doi.org/10.1161/CIRCRESAHA.107.165472
  5. Choo HS, Ko YK. Type 2 diabetes and mitochondria. Endocrinol Metab. 2006 ; 21(4) : 266-71.
  6. Suwa M, Egashira T, Nakano H, Sasaki H, Kumagai S. Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. J Appl Physiol (1985). 2006 ; 101(6) : 1685-92.
  7. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 ; 127(6) : 1109-22. https://doi.org/10.1016/j.cell.2006.11.013
  8. Choi CS. Potential therapeutic strategies for fat induced insulin resistance. Endocrinol Metab. 2009 ; 24(2) : 65-74.
  9. Association of professors of herbology, Korean medicine. Herbology. Seoul : Yonglimsa. 2006 : 579-80.
  10. Liu M, Wu K, Mao X, Wu Y, Ouyang J. Astragalus polysaccharide improves insulin sensitivity in KKAy mice: regulation of PKB/GLUT4 signaling in skeletal muscle. J Ethnopharmacol. 2010 ; 127(1) : 32-7. https://doi.org/10.1016/j.jep.2009.09.055
  11. Zou F, Mao XQ, Wang N, Liu J, Ou-Yang JP. Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK. Acta Pharmacol Sin. 2009 ; 30(12) : 1607-15. https://doi.org/10.1038/aps.2009.168
  12. Shao BM, Xu W, Dai H, Tu P, Li Z, Gao XM. A study on the immune receptors for polysaccharides from the roots of Astragalus membranaceus, a Chinese medicinal herb. Biochem Biophys Res Commun. 2004 ; 320(4) : 1103-11. https://doi.org/10.1016/j.bbrc.2004.06.065
  13. Chen R, Shao H, Lin S, Zhang JJ, Xu KQ. Treatment with Astragalus membranaceus produces antioxidative effects and attenuates intestinal mucosa injury induced by intestinal ischemia-reperfusion in rats. Am J Chin Med. 2011 ; 39(5) : 879-87. https://doi.org/10.1142/S0192415X11009275
  14. Li XT, Zhang YK, Kuang HX, Jin FX, Liu DW, Gao MB, et al. Mitochondrial protection and anti-aging activity of Astragalus polysaccharides and their potential mechanism. Int J Mol Sci. 2012 ; 13(2) : 1747-61. https://doi.org/10.3390/ijms13021747
  15. Canto C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol. 2009 ; 20(2) : 98-105. https://doi.org/10.1097/MOL.0b013e328328d0a4
  16. Gleyzer N, Vercauteren K, Scarpulla RC. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol. 2005 ; 25(4) : 1354-66. https://doi.org/10.1128/MCB.25.4.1354-1366.2005
  17. Rochard P, Rodier A, Casas F, Cassar-Malek I, Marchal-Victorion S, Daury L, et al. Mitochondrial activity is involved in the regulation of myoblast differentiation through myogenin expression and activity of myogenic factors. J Biol Chem. 2000 ; 275(4) : 2733-44. https://doi.org/10.1074/jbc.275.4.2733
  18. Dedieu S, Mazeres G, Cottin P, Brustis JJ. Involvement of myogenic regulator factors during fusion in the cell line C2C12. Int J Dev Biol. 2002 ; 46(2) : 235-41.

Cited by

  1. 부자추출물의 골격근 세포에서의 에너지 조절 작용 vol.16, pp.2, 2014, https://doi.org/10.15429/jkomor.2016.16.2.109
  2. 고지방식이로 유도된 비만형 동물모델에서 부자 물추출물의 비만 및 당대사 개선 효능 평가 vol.17, pp.1, 2014, https://doi.org/10.15429/jkomor.2017.17.1.29
  3. 최근 10년간 한방비만학회지의 연구동향 분석: 2010-2019년 한방비만학회지 게재논문을 중심으로 vol.20, pp.2, 2014, https://doi.org/10.15429/jkomor.2020.20.2.149