Korean J Physiol Pharmacol.  2017 Nov;21(6):651-656. 10.4196/kjpp.2017.21.6.651.

Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study

• Bang HS
• Seo DY
• Chung YM
• Kim DH
• Lee SJ
• Lee SR
• Kwak HB
• Kim TN
• Kim M
• Oh KM
• Son YJ
• Kim S
• Han J

• KMID: 2395260
• DOI: http://doi.org/10.4196/kjpp.2017.21.6.651

Abstract

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men.

Keyword

Resistance training; Resistance-trained men; Skeletal muscle damage markers; Ursolic acid

MeSH Terms

Adipose Tissue
Body Composition
Body Weight
Creatine
Creatine Kinase
Healthy Volunteers
Humans
Hydrocortisone
L-Lactate Dehydrogenase
Male
Muscle, Skeletal*
Myoglobin
Natriuretic Peptide, Brain
Pilot Projects*
Resistance Training*
Creatine
Creatine Kinase
Hydrocortisone
L-Lactate Dehydrogenase
Myoglobin
Natriuretic Peptide, Brain

Figure

• 

  Fig. 1 Percentage of changes in markers of skeletal muscle damage at baseline and after 8 weeks of RT and RT+UA in resistance-trained men. (A) B-type natriuretic peptide (BNP), (B) creatine kinase (CK), (C) creatine kinase–myocardial band (CK-MB), (D) cortisol, (E) lactate dehydrogenase (LDH), and (F) myoglobin. Data are presented as mean±SE. *p<0.05, vs. the RT group.

Reference

1. Mendes R, Sousa N, Themudo-Barata J, Reis V. Impact of a community-based exercise programme on physical fitness in middle-aged and older patients with type 2 diabetes. Gac Sanit. 2016; 30:215–220.

2. Goldberg AL, Etlinger JD, Goldspink DF, Jablecki C. Mechanism of work-induced hypertrophy of skeletal muscle. Med Sci Sports. 1975; 7:185–198.

3. Seo DY, Lee SR, Kim N, Ko KS, Rhee BD, Han J. Humanized animal exercise model for clinical implication. Pflugers Arch. 2014; 466:1673–1687.

4. Popov DV, Lysenko EA, Bachinin AV, Miller TF, Kurochkina NS, Kravchenko IV, Furalyov VA, Vinogradova OL. Influence of resistance exercise intensity and metabolic stress on anabolic signaling and expression of myogenic genes in skeletal muscle. Muscle Nerve. 2015; 51:434–442.

5. Kim JS, Yoon DH, Kim HJ, Choi MJ, Song W. Resistance exercise reduced the expression of fibroblast growth factor-2 in skeletal muscle of aged mice. Integr Med Res. 2016; 5:230–235.

6. Clarkson PM, Nosaka K, Braun B. Muscle function after exerciseinduced muscle damage and rapid adaptation. Med Sci Sports Exerc. 1992; 24:512–520.

7. Moat SJ, Korpimäki T, Furu P, Hakala H, Polari H, Meriö L, Mäkinen P, Weeks I. Characterization of a blood spot creatine kinase skeletal muscle isoform immunoassay for high-throughput newborn screening of duchenne muscular dystrophy. Clin Chem. 2017; 63:908–914.

8. Chen YC, Sumandea MP, Larsson L, Moss RL, Ge Y. Dissecting human skeletal muscle troponin proteoforms by top-down mass spectrometry. J Muscle Res Cell Motil. 2015; 36:169–181.

9. Larsen AI, Skadberg Ø, Aarsland T, Kvaløy JT, Lindal S, Omland T, Dickstein K. B-type natriuretic peptide is related to histological skeletal muscle abnormalities in patients with chronic heart failure. Int J Cardiol. 2009; 136:358–362.

10. Washington TA, Healey JM, Thompson RW, Lowe LL, Carson JA. Lactate dehydrogenase regulation in aged skeletal muscle: Regulation by anabolic steroids and functional overload. Exp Gerontol. 2014; 57:66–74.

11. Stauber WT, Clarkson PM, Fritz VK, Evans WJ. Extracellular matrix disruption and pain after eccentric muscle action. J Appl Physiol (1985). 1990; 69:868–874.

12. Takekura H, Fujinami N, Nishizawa T, Ogasawara H, Kasuga N. Eccentric exercise-induced morphological changes in the membrane systems involved in excitation-contraction coupling in rat skeletal muscle. J Physiol. 2001; 533:571–583.

13. Koskinen SO, Wang W, Ahtikoski AM, Kjaer M, Han XY, Komulainen J, Kovanen V, Takala TE. Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content. Am J Physiol Regul Integr Comp Physiol. 2001; 280:R1292–R1300.

14. Lieber RL, Fridén J. Selective damage of fast glycolytic muscle fibres with eccentric contraction of the rabbit tibialis anterior. Acta Physiol Scand. 1988; 133:587–588.

15. Fridén J, Seger J, Ekblom B. Sublethal muscle fibre injuries after high-tension anaerobic exercise. Eur J Appl Physiol Occup Physiol. 1988; 57:360–368.

16. Seo DY, McGregor RA, Noh SJ, Choi SJ, Mishchenko NP, Fedoreyev SA, Stonik VA, Han J. Echinochrome a improves exercise capacity during short-term endurance training in rats. Mar Drugs. 2015; 13:5722–5731.

17. Seo DY, Kwak HB, Lee SR, Cho YS, Song IS, Kim N, Bang HS, Rhee BD, Ko KS, Park BJ, Han J. Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5 and circulating irisin in high-fat-diet rat models. Nutr Res Pract. 2014; 8:177–182.

18. Kunkel SD, Suneja M, Ebert SM, Bongers KS, Fox DK, Malmberg SE, Alipour F, Shields RK, Adams CM. mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass. Cell Metab. 2011; 13:627–638.

19. Volek JS. Influence of nutrition on responses to resistance training. Med Sci Sports Exerc. 2004; 36:689–696.

20. Klinkenberg LJ, Res PT, Haenen GR, Bast A, van Loon LJ, van Dieijen-Visser MP, Meex SJ. Effect of antioxidant supplementation on exercise-induced cardiac troponin release in cyclists: a randomized trial. PLoS One. 2013; 8:e79280.

21. Ma JQ, Ding J, Zhang L, Liu CM. Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK/NF-κB pathway. Environ Toxicol Pharmacol. 2014; 37:975–983.

22. Wang YL, Wang ZJ, Shen HL, Yin M, Tang KX. Effects of artesunate and ursolic acid on hyperlipidemia and its complications in rabbit. Eur J Pharm Sci. 2013; 50:366–371.

23. Kunkel SD, Elmore CJ, Bongers KS, Ebert SM, Fox DK, Dyle MC, Bullard SA, Adams CM. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One. 2012; 7:e39332.

24. Senthil S, Chandramohan G, Pugalendi KV. Isomers (oleanolic and ursolic acids) differ in their protective effect against isoproterenol-induced myocardial ischemia in rats. Int J Cardiol. 2007; 119:131–133.

25. Somova LI, Shode FO, Mipando M. Cardiotonic and antidysrhythmic effects of oleanolic and ursolic acids, methyl maslinate and uvaol. Phytomedicine. 2004; 11:121–129.

26. American College of Sports Medicine. American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009; 41:687–708.

27. Bang HS, Seo DY, Chung YM, Oh KM, Park JJ, Arturo F, Jeong SH, Kim N, Han J. Ursolic Acid-induced elevation of serum irisin augments muscle strength during resistance training in men. Korean J Physiol Pharmacol. 2014; 18:441–446.

28. Maisel A, Hollander JE, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R. Rapid Emergency Department Heart Failure Outpatient Trial investigators. Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT). A multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol. 2004; 44:1328–1333.

29. Steele J, Fisher J, Skivington M, Dunn C, Arnold J, Tew G, Batterham AM, Nunan D, O'Driscoll JM, Mann S, Beedie C, Jobson S, Smith D, Vigotsky A, Phillips S, Estabrooks P, Winett R. A higher effort-based paradigm in physical activity and exercise for public health: making the case for a greater emphasis on resistance training. BMC Public Health. 2017; 17:300.

30. Bellamy LM, Joanisse S, Grubb A, Mitchell CJ, McKay BR, Phillips SM, Baker S, Parise G. The acute satellite cell response and skeletal muscle hypertrophy following resistance training. PLoS One. 2014; 9:e109739.

31. Verdijk LB, Gleeson BG, Jonkers RA, Meijer K, Savelberg HH, Dendale P, van Loon LJ. Skeletal muscle hypertrophy following resistance training is accompanied by a fiber type-specific increase in satellite cell content in elderly men. J Gerontol A Biol Sci Med Sci. 2009; 64:332–339.

32. Vincent HK, Vincent KR. The effect of training status on the serum creatine kinase response, soreness and muscle function following resistance exercise. Int J Sports Med. 1997; 18:431–437.

33. Fehrenbach E, Niess AM, Schlotz E, Passek F, Dickhuth HH, Northoff H. Transcriptional and translational regulation of heat shock proteins in leukocytes of endurance runners. J Appl Physiol (1985). 2000; 89:704–710.

34. Hornemann T, Stolz M, Wallimann T. Isoenzyme-specific interaction of muscle-type creatine kinase with the sarcomeric M-line is mediated by NH(2)-terminal lysine charge-clamps. J Cell Biol. 2000; 149:1225–1234.

35. Johnston RD, Gibson NV, Twist C, Gabbett TJ, MacNay SA, Mac-Farlane NG. Physiological responses to an intensified period of rugby league competition. J Strength Cond Res. 2013; 27:643–654.

36. Bakhtiari N, Hosseinkhani S, Tashakor A, Hemmati R. Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal muscle rejuvenation. Med Hypotheses. 2015; 85:1–6.

37. Chu X, He X, Shi Z, Li C, Guo F, Li S, Li Y, Na L, Sun C. Ursolic acid increases energy expenditure through enhancing free fatty acid uptake and β-oxidation via an UCP3/AMPK-dependent pathway in skeletal muscle. Mol Nutr Food Res. 2015; 59:1491–1503.

38. Katashima CK, Silva VR, Gomes TL, Pichard C, Pimentel GD. Ursolic acid and mechanisms of actions on adipose and muscle tissue: a systematic review. Obes Rev. 2017; 18:700–711.

39. Saravanan R, Viswanathan P, Pugalendi KV. Protective effect of ursolic acid on ethanol-mediated experimental liver damage in rats. Life Sci. 2006; 78:713–718.

40. Radhiga T, Rajamanickam C, Senthil S, Pugalendi KV. Effect of ursolic acid on cardiac marker enzymes, lipid profile and macroscopic enzyme mapping assay in isoproterenol-induced myocardial ischemic rats. Food Chem Toxicol. 2012; 50:3971–3977.