DOI QR코드

DOI QR Code

Gynostemma pentaphyllum extract and its active component gypenoside L improve the exercise performance of treadmill-trained mice

  • Kim, Yoon Hee (Technology Development Center, BTC Corporation) ;
  • Jung, Jae In (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Jeon, Young Eun (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Kim, So Mi (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Hong, Su Hee (Regional Strategic Industry Innovation Center, Hallym University) ;
  • Kim, Tae Young (Technology Development Center, BTC Corporation) ;
  • Kim, Eun Ji (Regional Strategic Industry Innovation Center, Hallym University)
  • Received : 2021.07.08
  • Accepted : 2021.09.02
  • Published : 2022.06.01

Abstract

BACKGROUND/OBJECTIVES: The effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G. pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined. MATERIALS/METHODS: This study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed. RESULTS: The ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferator-activated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation. CONCLUSIONS: These results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.

Keywords

Acknowledgement

The authors wish to thank the BTC Corporation for providing the Gynostemma pentaphyllum extract (GPE) and gypenoside L (GL).

References

  1. Matsukawa T, Motojima H, Sato Y, Takahashi S, Villareal MO, Isoda H. Upregulation of skeletal muscle PGC-1α through the elevation of cyclic AMP levels by cyanidin-3-glucoside enhances exercise performance. Sci Rep 2017;7:44799. https://doi.org/10.1038/srep44799
  2. 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 2011;286:10605-17. https://doi.org/10.1074/jbc.M110.211466
  3. Wang H, Li C, Wu X, Lou X. Effects of Gynostemma pentaphyllum (Thunb.) Makino polysaccharides supplementation on exercise tolerance and oxidative stress induced by exhaustive exercise in rats. Afr J Agric Res 2012;7:2632-8.
  4. Lin-Na S, Yong-Xiu S. Effects of polysaccharides from Gynostemma pentaphyllum (Thunb.), Makino on physical fatigue. Afr J Tradit Complement Altern Med 2014;11:112-7. https://doi.org/10.4314/ajtcam.v11i3.17
  5. Shang X, Chao Y, Zhang Y, Lu C, Xu C, Niu W. Immunomodulatory and antioxidant effects of polysaccharides from Gynostemma pentaphyllum Makino in immunosuppressed mice. Molecules 2016;21:1085. https://doi.org/10.3390/molecules21081085
  6. Quan Y, Qian MZ. Effect and mechanism of gypenoside on the inflammatory molecular expression in high-fat induced atherosclerosis rats. Zhongguo Zhong Xi Yi Jie He Za Zhi 2010;30:403-6.
  7. Cai H, Liang Q, Ge G. Gypenoside attenuates beta amyloid-induced inflammation in N9 microglial cells via SOCS1 signaling. Neural Plast 2016;2016:6362707.
  8. Liou CJ, Huang WC, Kuo ML, Yang RC, Shen JJ. Long-term oral administration of Gynostemma pentaphyllum extract attenuates airway inflammation and Th2 cell activities in ovalbumin-sensitized mice. Food Chem Toxicol 2010;48:2592-8. https://doi.org/10.1016/j.fct.2010.06.020
  9. Muller C, Gardemann A, Keilhoff G, Peter D, Wiswedel I, Schild L. Prevention of free fatty acid-induced lipid accumulation, oxidative stress, and cell death in primary hepatocyte cultures by a Gynostemma pentaphyllum extract. Phytomedicine 2012;19:395-401. https://doi.org/10.1016/j.phymed.2011.12.002
  10. Gou SH, Huang HF, Chen XY, Liu J, He M, Ma YY, Zhao XN, Zhang Y, Ni JM. Lipid-lowering, hepatoprotective, and atheroprotective effects of the mixture Hong-Qu and gypenosides in hyperlipidemia with NAFLD rats. J Chin Med Assoc 2016;79:111-21. https://doi.org/10.1016/j.jcma.2015.09.002
  11. la Cour B, Molgaard P, Yi Z. Traditional Chinese medicine in treatment of hyperlipidaemia. J Ethnopharmacol 1995;46:125-9. https://doi.org/10.1016/0378-8741(95)01234-5
  12. Wang M, Wang F, Wang Y, Ma X, Zhao M, Zhao C. Metabonomics study of the therapeutic mechanism of Gynostemma pentaphyllum and atorvastatin for hyperlipidemia in rats. PLoS One 2013;8:e78731. https://doi.org/10.1371/journal.pone.0078731
  13. Lee HS, Lim SM, Jung JI, Kim SM, Lee JK, Kim YH, Cha KM, Oh TK, Moon JM, Kim TY, et al. Gynostemma pentaphyllum extract ameliorates high-fat diet-induced obesity in C57BL/6N mice by upregulating SIRT1. Nutrients 2019;11:2475. https://doi.org/10.3390/nu11102475
  14. Huyen VT, Phan DV, Thang P, Hoa NK, Ostenson CG. Gynostemma pentaphyllum tea improves insulin sensitivity in type 2 diabetic patients. J Nutr Metab 2013;2013:765383. https://doi.org/10.1155/2013/765383
  15. Keilhoff G, Esser T, Titze M, Ebmeyer U, Schild L. Gynostemma pentaphyllum is neuroprotective in a rat model of cardiopulmonary resuscitation. Exp Ther Med 2017;14:6034-46.
  16. Li Y, Lin W, Huang J, Xie Y, Ma W. Anti-cancer effects of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan). Chin Med 2016;11:43. https://doi.org/10.1186/s13020-016-0114-9
  17. Kao TH, Huang SC, Inbaraj BS, Chen BH. Determination of flavonoids and saponins in Gynostemma pentaphyllum (Thunb.) Makino by liquid chromatography-mass spectrometry. Anal Chim Acta 2008;626:200-11. https://doi.org/10.1016/j.aca.2008.07.049
  18. Xie Z, Liu W, Huang H, Slavin M, Zhao Y, Whent M, Blackford J, Lutterodt H, Zhou H, Chen P, et al. Chemical composition of five commercial Gynostemma pentaphyllum samples and their radical scavenging, antiproliferative, and anti-inflammatory properties. J Agric Food Chem 2010;58:11243-9. https://doi.org/10.1021/jf1026372
  19. Lin CC, Huang PC, Lin JM. Antioxidant and hepatoprotective effects of Anoectochilus formosanus and Gynostemma pentaphyllum. Am J Chin Med 2000;28:87-96. https://doi.org/10.1142/S0192415X00000118
  20. Liu J, Zhang L, Ren Y, Gao Y, Kang L, Qiao Q. Anticancer and immunoregulatory activity of Gynostemma pentaphyllum polysaccharides in H22 tumor-bearing mice. Int J Biol Macromol 2014;69:1-4. https://doi.org/10.1016/j.ijbiomac.2014.05.014
  21. Attawish A, Chivapat S, Phadungpat S, Bansiddhi J, Techadamrongsin Y, Mitrijit O, Chaorai B, Chavalittumrong P. Chronic toxicity of Gynostemma pentaphyllum. Fitoterapia 2004;75:539-51. https://doi.org/10.1016/j.fitote.2004.04.010
  22. Chi AP, Chen JP, Wang ZZ, Xiong ZY, Li QX. Morphological and structural characterization of a polysaccharide from Gynostemma pentaphyllum Makino and its anti-exercise fatigue activity. Carbohydr Polym 2008;74:868-74. https://doi.org/10.1016/j.carbpol.2008.05.010
  23. Yang X, Zhao Y, Yang Y, Ruan Y. Isolation and characterization of immunostimulatory polysaccharide from an herb tea, Gynostemma pentaphyllum Makino. J Agric Food Chem 2008;56:6905-9. https://doi.org/10.1021/jf801101u
  24. Ding YJ, Tang KJ, Li FL, Hu QL. Effects of gypenosides from Gynostemma pentaphyllum supplementation on exercise-induced fatigue in mice. Afr J Agric Res 2010;5:707-11.
  25. Tadaishi M, Miura S, Kai Y, Kano Y, Oishi Y, Ezaki O. Skeletal muscle-specific expression of PGC-1α-b, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake. PLoS One 2011;6:e28290. https://doi.org/10.1371/journal.pone.0028290
  26. Kim YH, Kim SM, Lee JK, Jo SK, Kim HJ, Cha KM, Lim CY, Moon JM, Kim TY, Kim EJ. Efficacy of Gynostemma pentaphyllum extract in anti-obesity therapy. Rec Nat Prod 2020;14:116-28. https://doi.org/10.25135/rnp.146.19.05.1270
  27. Kim YH, Jung JI, Jeon YE, Kim SM, Oh TK, Lee J, Moon JM, Kim TY, Kim EJ. Gynostemma pentaphyllum extract and gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes. Nutr Res Pract 2021;15:e45.
  28. Hearris MA, Hammond KM, Fell JM, Morton JP. Regulation of muscle glycogen metabolism during exercise: implications for endurance performance and training adaptations. Nutrients 2018;10:298. https://doi.org/10.3390/nu10030298
  29. Jensen J, Rustad PI, Kolnes AJ, Lai YC. The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise. Front Physiol 2011;2:112. https://doi.org/10.3389/fphys.2011.00112
  30. Cheng CF, Ku HC, Lin H. PGC-1α as a pivotal factor in lipid and metabolic regulation. Int J Mol Sci 2018;19:3447. https://doi.org/10.3390/ijms19113447
  31. Kang C, Li Ji L. Role of PGC-1α signaling in skeletal muscle health and disease. Ann N Y Acad Sci 2012;1271:110-7. https://doi.org/10.1111/j.1749-6632.2012.06738.x
  32. Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1α expression. J Biol Chem 2007;282:194-9. https://doi.org/10.1074/jbc.M606116200
  33. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY, Krauss S, Mootha VK, Lowell BB, Spiegelman BM. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1. Mol Cell 2001;8:971-82. https://doi.org/10.1016/S1097-2765(01)00390-2
  34. Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proc Natl Acad Sci U S A 2007;104:12017-22. https://doi.org/10.1073/pnas.0705070104
  35. Wan JJ, Qin Z, Wang PY, Sun Y, Liu X. Muscle fatigue: general understanding and treatment. Exp Mol Med 2017;49:e384. https://doi.org/10.1038/emm.2017.194
  36. Facey A, Irving R, Dilworth L. Overview of lactate metabolism and the implications for athletes. J Sports Sci Med 2013;l:42-6.
  37. Hirabara SM, Silveira LR, Abdulkader FR, Alberici LC, Procopio J, Carvalho CR, Pithon-Curi TC, Curi R. Role of fatty acids in the transition from anaerobic to aerobic metabolism in skeletal muscle during exercise. Cell Biochem Funct 2006;24:475-81. https://doi.org/10.1002/cbf.1327
  38. DeFronzo RA. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988;37:667-87. https://doi.org/10.2337/diab.37.6.667
  39. Liu Y, Liu C. Antifatigue and increasing exercise performance of Actinidia arguta crude alkaloids in mice. J Food Drug Anal 2016;24:738-45. https://doi.org/10.1016/j.jfda.2016.03.001
  40. Martin WH 3rd, Dalsky GP, Hurley BF, Matthews DE, Bier DM, Hagberg JM, Rogers MA, King DS, Holloszy JO. Effect of endurance training on plasma free fatty acid turnover and oxidation during exercise. Am J Physiol 1993;265:E708-14.
  41. Horowitz JF, Klein S. Lipid metabolism during endurance exercise. Am J Clin Nutr 2000;72:558S-563S. https://doi.org/10.1093/ajcn/72.2.558S
  42. Li F, Li J, Li S, Guo S, Li P. Modulatory effects of Chinese herbal medicines on energy metabolism in ischemic heart diseases. Front Pharmacol 2020;11:995. https://doi.org/10.3389/fphar.2020.00995
  43. Kang D, Hamasaki N. Mitochondrial transcription factor A in the maintenance of mitochondrial DNA: overview of its multiple roles. Ann N Y Acad Sci 2005;1042:101-8. https://doi.org/10.1196/annals.1338.010
  44. Rowe GC, Jiang A, Arany Z. PGC-1 coactivators in cardiac development and disease. Circ Res 2010;107:825-38. https://doi.org/10.1161/CIRCRESAHA.110.223818
  45. Nalbandian M, Takeda M. Lactate as a signaling molecule that regulates exercise induced adaptations. Biology (Basel) 2016;5:38. https://doi.org/10.3390/biology5040038