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Ashitaba and red ginseng complex stimulates exercise capacity by increasing mitochondrial biogenesis

미토콘드리아 생합성 촉진을 통한 신선초와 홍삼 복합물의 운동수행능력 증가 효과

  • 김창희 (연세대학교 생명공학과) ;
  • 김미보 (연세대학교 생명공학과) ;
  • 이승호 ((주)카인즈 바이오틱스 R&BD팀) ;
  • 김예진 ((주)카인즈 바이오틱스 R&BD팀) ;
  • 황재관 (연세대학교 생명공학과)
  • Received : 2017.07.21
  • Accepted : 2017.09.24
  • Published : 2017.12.31

Abstract

Mitochondrial biogenesis-a process that leads to an increment in the number and density of mitochondria, improves physical performance and body health by enhancing exercise capacity. In the present study, we investigated the stimulatory effect of Ashitaba and red ginseng complex (ARC) on exercise capacity in L6 skeletal muscle cells and mice. In L6 skeletal muscle cells, ARC increased the mitochondrial contents and ATP production by activating AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-$1{\alpha}$) and up-regulating the mRNA expression of nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM). In the animal experiments, mice treated with ARC showed an increment in exercise capacity as compared with mice treated with Ashitaba extract or red ginseng extract alone. These studies indicate that ARC might serve as a potential natural candidate for enhancing exercise capacity by stimulation of mitochondrial biogenesis.

Keywords

Ashitaba;Exercise capacity;Mitochondrial biogenesis;Red ginseng

References

  1. Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr. Physiol. 2: 1143-1211 (2012)
  2. Golbidi S, Mesdaghinia A, Laher I. Exercise in the metabolic syndrome. Oxid. Med. Cell. Longev. 2012: 349710 (2012)
  3. Na C, Hong CY, Na D, Kim JB, Yoon SY, Lee S, Dong M. Hotwater extract of Hovenia dulcis peduncle improves exercise performance and anti-fatigue effects in mice. Korean J. Pharmacogn. 44: 83-90 (2013)
  4. Na C, Kim HK, Kim JB, Roh HJ, Um NN, Noh H, Na D, Dong M, Hong CY. The effects of Hovenia dulcis fruit hot water extracts on anti-fatigue and improvement of the exercise performance in SD rats. J. Pharm. Soc. Korea 57: 348-356 (2013)
  5. Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat. Rev. Endocrinol. 8: 457-465 (2012) https://doi.org/10.1038/nrendo.2012.49
  6. Egan B, Zierath JR. Exercise metabolisms and the molecular regulation of skeletal muscle adaptation. Cell Metab. 17: 162-184 (2013) https://doi.org/10.1016/j.cmet.2012.12.012
  7. Scarpulla RC, Vega RB, Kelly DP. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol. Metab. 23: 459-466 (2012) https://doi.org/10.1016/j.tem.2012.06.006
  8. Safdar A, Little JP, Stokl AJ, Hettinga BP, Akhtar M, Tarnopolsky MA. Exercise increases mitochondrial PGC-1alpha content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J. Biol. Chem. 286: 10605-10617 (2011) https://doi.org/10.1074/jbc.M110.211466
  9. Bruce CR, Thrush AB, Mertz VA, Bezaire V, Chabowski A, Heigenhauser GJ, Dyck DJ. Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am. J. Physiol. Endocrinol. Metab. 291: E99-E107 (2006) https://doi.org/10.1152/ajpendo.00587.2005
  10. Canto C, Auwerx J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr. Opin. Lipidol. 20: 98-105 (2009) https://doi.org/10.1097/MOL.0b013e328328d0a4
  11. Kim B. The effects of endurance training on mitochondrial Tfam and PGC-$1{\alpha}$ mRNA in GK rats. Korean J. Sport Sci. 17: 863-872 (2008)
  12. Kim SN, Ha YW, Shin H, Son SH, Wu SJ, Kim YS. Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control. J. Pharm. Biomed. Anal. 45: 164-170 (2007) https://doi.org/10.1016/j.jpba.2007.05.001
  13. Byeon SE, Lee J, Kim JH, Yang WS, Kwak YS, Kim SY, Choung ES, Rhee MH, Cho JY. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean red ginseng. Mediat. Inflamm. 2012: 732860 (2012)
  14. Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, Shim I. Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. Journal of pharmacological sciences. J. Pharmacol. Sci. 97: 124-131 (2005) https://doi.org/10.1254/jphs.FP0040184
  15. Choi KT. Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C.A. Meyer. Acta Pharmacol. Sin. 29: 1109-1118 (2008) https://doi.org/10.1111/j.1745-7254.2008.00869.x
  16. Cabral de Oliveira AC, Perez AC, Merino G, Prieto JG, Alvarez AI. Protective effects of Panax ginseng on muscle injury and inflammation after eccentric exercise. Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 130: 369-377 (2001) https://doi.org/10.1016/S1532-0456(01)00262-9
  17. Ramesh T, Kim SW, Hwang SY, Sohn SH, Yoo SK, Kim SK. Panax ginseng reduces oxidative stress and restores antioxidant capacity in aged rats. Nutr. Res. 32: 718-726 (2012) https://doi.org/10.1016/j.nutres.2012.08.005
  18. Kim TH, Son YK, Hwang KH, Kim M. Effects of Angelica keiskei Koidzumi and turmeric extract supplementation on serum lipid parameters in hypercholesterolemic diet or P-407-induced hyperlipidemic rat. J. Korean Soc. Food Sci. Nutr. 37: 708-713 (2008) https://doi.org/10.3746/jkfn.2008.37.6.708
  19. Zhang T, Yamashita Y, Yasuda M, Yamamoto N, Ashida H. Ashitaba (Angelica keiskei) extract prevents adiposity in high-fat dietfed C57BL/6 mice. Food Funct. 6: 135-145 (2015)
  20. Enoki T, Ohnogi H, Nagamine K, Kudo Y, Sugiyama K, Tanabe M, Kobayashi E, Sagawa H, Kato I. Antidiabetic activities of chalcones isolated from a Japanese herb, Angelica keiskei. J. Agric. Food Chem. 55: 6013-6017 (2007) https://doi.org/10.1021/jf070720q
  21. Kwon D, Yoon S, Carter O, Bailey GS, Dashwood RH. Antioxidant and antigenotoxic activities of Angelica keiskei, Oenanthe javanica and Brassica oleracea in the Salmonella mutagenicity assay and in HCT116 human colon cancer cells. Biofactors 26: 231-244 (2006) https://doi.org/10.1002/biof.5520260402
  22. Akihisa T, Tokuda H, Ukiya M, Iizuka M, Schneider S, Ogasawara K, Mukainaka T, Iwatsuki K, Suzuki T, Nishino H. Chalcones, coumarins, and flavanones from the exudate of Angelica keiskei and their chemopreventive effects. Cancer Lett. 201: 133-137 (2003) https://doi.org/10.1016/S0304-3835(03)00466-X
  23. Kim T, Kim MB, Kim C, Jung HY, Hwang JK. Standardized Boesenbergia pandurata extract stimulates exercise endurance through increasing mitochondrial biogenesis. J. Med. Food 19: 692-700 (2016) https://doi.org/10.1089/jmf.2015.3630
  24. Lee GS, Lee KM, Kim SH, Jeong NJ, Kim YJ, Jung JY, Kang TJ. Protective effects of SAPP, a novel herbal complex, in acute hepatotoxic mouse model. Nat. Prod. Sci. 19: 173-178 (2013)
  25. Kim JH, Kim J, Park Y. Trans-10, cis-12 conjugated linoleic acid enhances endurance capacity by increasing fatty acid oxidation reducing glycogen utilization in mice. Lipids 47: 855-863 (2012) https://doi.org/10.1007/s11745-012-3698-6
  26. Jung HY, Lee AN, Song TJ, An HS, Kim YH, Kim KD, Kim IB, Kim KS, Han BS, Kim JB. Korean Mistletoe (Viscum album coloratum) extract improves endurance capacity in mice by stimulating mitochondrial activity. J. Med. Food 15: 621-628 (2012) https://doi.org/10.1089/jmf.2010.1469
  27. Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, Hubbard BP, Varela AT, Davis JG, Varamini B, Hafner A, Moaddel R, Rolo AP, Coppari R, Palmeira CM, de Cabo R, Baur JA, Sinclair DA. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab. 15: 675-690 (2012) https://doi.org/10.1016/j.cmet.2012.04.003
  28. Yuan HD, Huang B, Quan HY, Chung SH. Ginsenoside 20(R)-Rg3 stimulates glucose uptake in C2C12 myotubes via CaMKKAMPK pathways. Food Sci. Biotechnol. 19: 1277-1282 (2010) https://doi.org/10.1007/s10068-010-0182-z
  29. Lee HM, Lee OH, Kim KJ, Lee BY. Ginsenoside Rg1 promotes glucose uptake through activated AMPK pathway in insulin-resistant muscle cells. Phytother. Res. 26: 1017-1022 (2012) https://doi.org/10.1002/ptr.3686
  30. Kawabata K, Sawada K, Ikeda K, Fukuda I, Kawasaki K, Yamamoto N, Ashida H. Prenylated chalcones 4-hydroxyderricin and xanthoangelol stimulate glucose uptake in skeletal muscle cells by inducing GLUT4 translocation. Mol. Nutr. Food Res. 55: 467-475 (2011) https://doi.org/10.1002/mnfr.201000267
  31. Park SJ, Lim KH, Noh JH, Jeong EJ, Kim YS, Han BS, Lee SH, Moon KS. Subacute oral toxicity study of Korean red ginseng extract in Sprague-Dawley rats. Toxicol. Res. 29: 285-292 (2013) https://doi.org/10.5487/TR.2013.29.4.285
  32. Nagata J, Morino T, Saito M. Effects of dietary Angelica keiskei on serum and liver lipid profiles, and body fat accumulations in rats. J. Nutr. Sci. Vitaminol. 53: 133-137 (2007) https://doi.org/10.3177/jnsv.53.133
  33. Lee IH, Kim MJ, Park SW, Park YE, Kim HM, Lew JH. Ergogenic effect of Cervi Cornu and CoenzymeQ10 complex. J. Int. Korean Med. 36: 297-307 (2015)
  34. Kim K, You Y. Stimulatory Effects of extracts of inner bark from Tabebuia avellanedae on exercise endurance capacity. J. Korean Soc. Food Sci. Nutr. 43: 1937-s1941 (2014) https://doi.org/10.3746/jkfn.2014.43.12.1937
  35. Wang J, Li S, Fan Y, Chen Y, Liu D, Cheng H, Gao X, Zhou Y. Anti-fatigue activity of the water-soluble polysaccharides isolated from Panax ginseng C. A. Meyer. J. Ethnopharmacol. 130: 421-423 (2010) https://doi.org/10.1016/j.jep.2010.05.027
  36. Lee ES, Yang YJ, LEE JH, Yoon YS. Effect of high-dose ginsenoside complex (UG0172) supplementation on physical performance of healthy adults during a 12-week supervised exercise program: A randomized placebo-controlled clinical trial. J. Ginseng Res. in press (2017)
  37. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 22: 659-661 (2008) https://doi.org/10.1096/fj.07-9574LSF
  38. Jeong HW, Cho SY, Kim S, Shin ES, Kim JM, Song MJ, Park PJ, Sohn JH, Park H, Seo DB, Kim WG, Lee SJ. Chitooligosaccharide induces mitochondrial biogenesis and increases exercise endurance through the activation of Sirt1 and AMPK in rats. PLoS One 7: e40073 (2012) https://doi.org/10.1371/journal.pone.0040073
  39. Park KS, Park KI, Kim JW, Yun YJ, Kim SH, Lee CH, Park JW, Lee JM. Efficacy and safety of Korean red ginseng for cold hypersensitivity in the hands and feet: A randomized, doubleblind, placebo-controlled trial. J. Ethnopharmacol. 158: 25-32 (2014) https://doi.org/10.1016/j.jep.2014.09.028
  40. Noh HM, Ahn EM, Yun JM, Cho BL, Paek YJ. Angelica keiskei Koidzumi extracts improve some markers of liver function in habitual alcohol drinkers: A randomized double-blind clinical trial. J. Med. Food 18: 166-172 (2015) https://doi.org/10.1089/jmf.2014.3222