Leucine and glycine dipeptides of porcine placenta ameliorate physical fatigue through enhancing dopaminergic systems

  • Authors:
    • Na‑Ra Han
    • Hee‑Yun Kim
    • Na‑Rae Kim
    • Won‑Kyung Lee
    • Hyein Jeong
    • Hyung‑Min Kim
    • Hyun‑Ja Jeong
  • View Affiliations

  • Published online on: December 20, 2017     https://doi.org/10.3892/mmr.2017.8335
  • Pages: 4120-4130
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Abstract

Fatigue is a common and serious health problem, and various dietary interventions have previously been employed to ameliorate fatigue. The aim of the current study was to investigate the anti‑fatigue effects of Danish porcine placenta (DPP) and its major dipeptides, including leucine‑glycine (LG) and glycine‑leucine (GL). The anti‑fatigue effects of orally administered DPP, LG and GL were determined using a treadmill exercise test and a forced swimming test (FST) in mice. Additionally, the anti‑inflammatory effects of DPP, LG and GL were investigated in activated splenocytes. The results demonstrated that oral treatment of mice with DPP, LG and GL increased the time to exhaustion during treadmill exercise. Furthermore, DPP, LG and GL enhanced the levels of dopamine, brain‑derived neurotrophic factor and phosphorylated-extracellular signal‑regulated kinase in the brains of mice with treadmill exercise‑induced exhaustive fatigue, and decreased levels of certain proinflammatory cytokines in the serum and spleen, as determined by ELISA and western blot analysis. Following treadmill exercise, commercial kits were employed to demonstrate that DPP, LG and GL reduced the levels of lactate dehydrogenase, lactate, creatine kinase, blood urea nitrogen, alanine transaminase and aspartate transaminase in the muscle and/or serum of mice. In addition, DPP, LG and GL enhanced the muscle and liver glycogen levels, catalase activity in the liver and serum superoxide dismutase activity. DPP, LG and GL also increased the proliferation of splenocytes and inhibited proinflammatory cytokine production by reducing the activation of caspase‑1 and nuclear factor‑κB in activated splenocytes, as determined by MTT assays, ELISA and western blotting, respectively. Furthermore, DPP, LG and GL reduced immobility time in the FST in mice. In conclusion, DPP may limit intensive exercise‑induced fatigue by increasing dopaminergic systems and inhibiting inflammatory responses.

References

1 

Gandevia SC: Spinal and supraspinal factors in human muscle fatigue. Physiol Rev. 81:1725–1789. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Meeusen R and Watson P: Amino acids and the brain: Do they play a role in ‘central fatigue’? Int J Sport Nutr Exerc Metab. 17 Suppl:S37–S46. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Balthazar CH, Leite LH, Rodrigues AG and Coimbra CC: Performance-enhancing and thermoregulatory effects of intracerebroventricular dopamine in running rats. Pharmacol Biochem Behav. 93:465–469. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Chaouloff F: Physical exercise and brain monoamines: A review. Acta Physiol Scand. 137:1–13. 1989. View Article : Google Scholar : PubMed/NCBI

5 

Basu S and Dasgupta PS: Dopamine, a neurotransmitter, influences the immune system. J Neuroimmunol. 102:113–124. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Meeusen R: Exercise, nutrition and the brain. Sports Med. 44 Suppl 1:S47–S56. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Razgado-Hernandez LF, Espadas-Alvarez AJ, Reyna-Velazquez P, Sierra-Sanchez A, Anaya-Martinez V, Jimenez-Estrada I, Bannon MJ, Martinez-Fong D and Aceves-Ruiz J: The transfection of BDNF to dopamine neurons potentiates the effect of dopamine D3 receptor agonist recovering the striatal innervation, dendritic spines and motor behavior in an aged rat model of Parkinson's disease. PLoS One. 10:e01173912015. View Article : Google Scholar : PubMed/NCBI

8 

Schmidt HD and Duman RS: The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol. 18:391–418. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Saligan LN, Lukkahatai N, Holder G, Walitt B and Machado-Vieira R: Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy. World J Biol Psychiatry. 27:608–614. 2016.

10 

Liburt NR, Adams AA, Betancourt A, Horohov DW and McKeever KH: Exercise-induced increases in inflammatory cytokines in muscle and blood of horses. Equine Vet J Suppl. 38:280–288. 2010. View Article : Google Scholar

11 

Felger JC and Miller AH: Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise. Front Neuroendocrinol. 33:315–327. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Koo HN, Lee JK, Hong SH and Kim HM: Herbkines increases physical stamina in mice. Biol Pharm Bull. 27:117–119. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Pall ML: Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Med Hypotheses. 54:115–125. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Coombes JS, Rowell B, Dodd SL, Demirel HA, Naito H, Shanely RA and Powers SK: Effects of vitamin E deficiency on fatigue and muscle contractile properties. Eur J Appl Physiol. 87:272–277. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Borah M, Sarma P and Das S: A study of the protective effect of triticum aestivum L. in an experimental animal model of chronic fatigue syndrome. Pharmacognosy Res. 6:285–291. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Finaud J, Lac G and Filaire E: Oxidative stress: Relationship with exercise and training. Sports Med. 36:327–358. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Tennant KF, Takacs SE, Gau JT, Clark BC and Russ DW: A preliminary study of symptomatic fatigue in rural older adults. Aging Clin Exp Res. 24:324–330. 2012.PubMed/NCBI

18 

Han NR, Kim KY, Kim MJ, Kim MH, Kim HM and Jeong HJ: Porcine placenta mitigates protein-energy malnutrition-induced fatigue. Nutrition. 29:1381–1387. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Wolfe RR: Protein supplements and exercise. Am J Clin Nutr. 72 2 Suppl:551S–557S. 2000.PubMed/NCBI

20 

Kim HY, Han NR, Kim NR, Lee M, Kim J, Kim CJ, Jeong HJ and Kim HM: Effect of fermented porcine placenta on physical fatigue in mice. Exp Biol Med (Maywood). 241:1985–1996. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Ye J, Shen C, Huang Y, Zhang X and Xiao M: Anti-fatigue activity of sea cucumber peptides prepared from Stichopus japonicus in an endurance swimming rat model. J Sci Food Agric. 97:4548–4556. 2017. View Article : Google Scholar : PubMed/NCBI

22 

van Buel EM, Sigrist H, Seifritz E, Fikse L, Bosker FJ, Schoevers RA, Klein HC, Pryce CR and Eisel UL: Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression. PLoS One. 12:e01846032017. View Article : Google Scholar : PubMed/NCBI

23 

Zhao YQ, Zeng L, Yang ZS, Huang FF, Ding GF and Wang B: Anti-fatigue effect by peptide fraction from protein hydrolysate of croceine croaker (pseudosciaena crocea) swim bladder through inhibiting the oxidative reactions including DNA damage. Mar Drugs. 14:pii: E2212016. View Article : Google Scholar

24 

Seo JH, Sung YH, Kim KJ, Shin MS, Lee EK and Kim CJ: Effects of Phellinus linteus administration on serotonin synthesis in the brain and expression of monocarboxylate transporters in the muscle during exhaustive exercise in rats. J Nutr Sci Vitaminol (Tokyo). 57:95–103. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Kumar V, Aneesh KA, Kshemada K, Ajith KGS, Binil RSS, Deora N, Sanjay G, Jaleel A, Muraleedharan TS, Anandan EM, et al: Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy. Sci Rep. 7:85882017. View Article : Google Scholar : PubMed/NCBI

26 

Motaghinejad M, Motevalian M, Asadi-Ghalehni M and Motaghinejad O: Attenuation of morphine withdrawal signs, blood cortisol and glucose level with forced exercise in comparison with clonidine. Adv Biomed Res. 3:1712014. View Article : Google Scholar : PubMed/NCBI

27 

Rim HK, Kim KY and Moon PD: Evidence of hydrolyzed traditional Korean red ginseng by malted barley on activation of receptor interacting proteins 2 and IkappaB kinase-beta in mouse peritoneal macrophages. TANG. 2:e372015.

28 

Jung HY, Lee AN, Song TJ, An HS, Kim YH, Kim KD, Kim IB, Kim KS, Han BS, Kim CH, et al: Korean mistletoe (Viscum album coloratum) extract improves endurance capacity in mice by stimulating mitochondrial activity. J Med Food. 15:621–628. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C (T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Teng YS and Wu D: Anti-fatigue effect of green tea polyphenols (−)-Epigallocatechin-3-Gallate (EGCG). Pharmacogn Mag. 13:326–331. 2017. View Article : Google Scholar : PubMed/NCBI

31 

Azzinnari D, Sigrist H, Staehli S, Palme R, Hildebrandt T, Leparc G, Hengerer B, Seifritz E and Pryce CR: Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function. Neuropharmacology. 85:328–341. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Flachenecker P, Bihler I, Weber F, Gottschalk M, Toyka KV and Rieckmann P: Cytokine mRNA expression in patients with multiple sclerosis and fatigue. Mult Scler. 10:165–169. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Marin H and Menza MA: Specific treatment of residual fatigue in depressed patients. Psychiatry (Edgmont). 1:12–18. 2004.PubMed/NCBI

34 

Bailey SP, Davis JM and Ahlborn EN: Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. J Appl Physiol (1985). 74:3006–3012. 1993. View Article : Google Scholar : PubMed/NCBI

35 

Gerald MC: Effects of (+)-amphetamine on the treadmill endurance performance of rats. Neuropharmacology. 17:703–704. 1978. View Article : Google Scholar : PubMed/NCBI

36 

Heyes MP, Garnett ES and Coates G: Nigrostriatal dopaminergic activity is increased during exhaustive exercise stress in rats. Life Sci. 42:1537–1542. 1988. View Article : Google Scholar : PubMed/NCBI

37 

Sorenson M, Jason L, Peterson J, Herrington J and Mathews H: Brain derived neurotrophic factor is decreased in chronic fatigue syndrome and multiple sclerosis. J Neurol Neurophysiol. 12 Suppl:S2–S13. 2014.

38 

Foley TE and Fleshner M: Neuroplasticity of dopamine circuits after exercise: Implications for central fatigue. Neuromolecular Med. 10:67–80. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Shen X, Li A, Zhang Y, Dong X, Shan T, Wu Y, Jia J and Hu Y: The effect of different intensities of treadmill exercise on cognitive function deficit following a severe controlled cortical impact in rats. Int J Mol Sci. 14:21598–21612. 2013. View Article : Google Scholar : PubMed/NCBI

40 

Feng P, Guan Z, Yang X and Fang J: Impairments of ERK signal transduction in the brain in a rat model of depression induced by neonatal exposure of clomipramine. Brain Res. 991:195–205. 2003. View Article : Google Scholar : PubMed/NCBI

41 

Dobryakova E, Genova HM, DeLuca J and Wylie GR: The dopamine imbalance hypothesis of fatigue in multiple sclerosis and other neurological disorders. Front Neurol. 6:522015. View Article : Google Scholar : PubMed/NCBI

42 

Rahimi E, Moghadasi M, Mahani MN, Torkfar A and Yadolazadeh A: Central and peripheral fatigue factors after an exhaustive aerobic exercise following creatine supplementation. Ann Biol Res. 3:4209–4214. 2012.

43 

Watanabe A, Kato N and Kato T: Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neurosci Res. 42:279–285. 2002. View Article : Google Scholar : PubMed/NCBI

44 

Su KY, Yu CY, Chen YW, Huang YT, Chen CT, Wu HF and Chen YL: Rutin, a flavonoid and principal component of saussurea involucrata, attenuates physical fatigue in a forced swimming mouse model. Int J Med Sci. 11:528–537. 2014. View Article : Google Scholar : PubMed/NCBI

45 

Calabrese F, Rossetti AC, Racagni G, Gass P, Riva MA and Molteni R: Brain-derived neurotrophic factor: A bridge between inflammation and neuroplasticity. Front Cell Neurosci. 8:4302014. View Article : Google Scholar : PubMed/NCBI

46 

Jason LA, Porter N, Herrington J, Sorenson M and Kubow S: Kindling and oxidative stress as contributors to myalgic encephalomyelitis/chronic fatigue syndrome. J Behav Neurosci Res. 7:1–17. 2009.PubMed/NCBI

47 

Suárez A, Guillamó E, Roig T, Blázquez A, Alegre J, Bermúdez J, Ventura JL, García-Quintana AM, Comella A, Segura R and Javierre C: Nitric oxide metabolite production during exercise in chronic fatigue syndrome: A case-control study. J Womens Health (Larchmt). 19:1073–1077. 2010. View Article : Google Scholar : PubMed/NCBI

48 

Liu J, Yeo HC, Overvik-Douki E, Hagen T, Doniger SJ, Chu DW, Brooks GA and Ames BN: Chronically and acutely exercised rats: Biomarkers of oxidative stress and endogenous antioxidants. J Appl Physiol (1985). 89:21–28. 2000. View Article : Google Scholar : PubMed/NCBI

49 

Wu C, Chen R, Wang XS, Shen B, Yue W and Wu Q: Antioxidant and anti-fatigue activities of phenolic extract from the seed coat of Euryale ferox Salisb. and identification of three phenolic compounds by LC-ESI-MS/MS. Molecules. 18:11003–11021. 2013. View Article : Google Scholar : PubMed/NCBI

50 

Lamkanfi M, Sarkar A, Vande Walle L, Vitari AC, Amer AO, Wewers MD, Tracey KJ, Kanneganti TD and Dixit VM: Inflammasome-dependent release of the alarmin HMGB1 in endotoxemia. J Immunol. 185:4385–4392. 2010. View Article : Google Scholar : PubMed/NCBI

51 

Sola-Penna M: Metabolic regulation by lactate. IUBMB Life. 60:605–608. 2008. View Article : Google Scholar : PubMed/NCBI

52 

Huang CC, Lin TJ, Lu YF, Chen CC, Huang CY and Lin WT: Protective effects of L-arginine supplementation against exhaustive exercise-induced oxidative stress in young rat tissues. Chin J Physiol. 52:306–315. 2009. View Article : Google Scholar : PubMed/NCBI

53 

Cruzat VF, Rogero MM and Tirapegui J: Effects of supplementation with free glutamine and the dipeptide alanyl-glutamine on parameters of muscle damage and inflammation in rats submitted to prolonged exercise. Cell Biochem Funct. 28:24–30. 2010. View Article : Google Scholar : PubMed/NCBI

54 

Huang WC, Chiu WC, Chuang HL, Tang DW, Lee ZM, Wei L, Chen FA and Huang CC: Effect of curcumin supplementation on physiological fatigue and physical performance in mice. Nutrients. 7:905–921. 2015. View Article : Google Scholar : PubMed/NCBI

55 

June CH, Ledbetter JA, Gillespie MM, Lindsten T and Thompson CB: T-cell proliferation involving the CD28 pathway is associated with cyclosporine-resistant interleukin 2 gene expression. Mol Cell Biol. 7:4472–4481. 1987. View Article : Google Scholar : PubMed/NCBI

56 

Suarez Butler MF, Langkamp-Henken B, Herrlinger-Garcia KA, Klash AE, Szczepanik ME, Nieves C Jr, Cottey RJ and Bender BS: Arginine supplementation enhances mitogen-induced splenocyte proliferation but does not affect in vivo indicators of antigen-specific immunity in mice. J Nutr. 135:1146–1150. 2005. View Article : Google Scholar : PubMed/NCBI

57 

Clancy RL, Gleeson M, Cox A, Callister R, Dorrington M, D'Este C, Pang G, Pyne D, Fricker P and Henriksson A: Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus. Br J Sports Med. 40:351–354. 2006. View Article : Google Scholar : PubMed/NCBI

58 

Cheng M, Nguyen MH, Fantuzzi G and Koh TJ: Endogenous interferon-gamma is required for efficient skeletal muscle regeneration. Am J Phys Cell Phys. 294:C1183–C1191. 2008. View Article : Google Scholar

59 

Fernstrom JD: Dietary amino acids and brain function. J Am Diet Assoc. 94:71–77. 1994. View Article : Google Scholar : PubMed/NCBI

60 

Davis JM, Alderson NL and Welsh RS: Serotonin and central nervous system fatigue: Nutritional considerations. Am J Clin Nutr. 72 2 Suppl:573S–578S. 2000.PubMed/NCBI

61 

Cruzat VF, Krause M and Newsholme P: Amino acid supplementation and impact on immune function in the context of exercise. J Int Soc Sports Nutr. 11:612014. View Article : Google Scholar : PubMed/NCBI

62 

Smith WA, Fry AC, Tschume LC and Bloomer RJ: Effect of glycine propionyl-L-carnitine on aerobic and anaerobic exercise performance. Int J Sport Nutr Exerc Metab. 18:19–36. 2008. View Article : Google Scholar : PubMed/NCBI

63 

Favano A, Santos-Silva PR, Nakano EY, Pedrinelli A, Hernandez AJ and Greve JM: Peptide glutamine supplementation for tolerance of intermittent exercise in soccer players. Clinics (Sao Paulo). 63:27–32. 2008. View Article : Google Scholar : PubMed/NCBI

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APA
Han, N., Kim, H., Kim, N., Lee, W., Jeong, H., Kim, H., & Jeong, H. (2018). Leucine and glycine dipeptides of porcine placenta ameliorate physical fatigue through enhancing dopaminergic systems. Molecular Medicine Reports, 17, 4120-4130. https://doi.org/10.3892/mmr.2017.8335
MLA
Han, N., Kim, H., Kim, N., Lee, W., Jeong, H., Kim, H., Jeong, H."Leucine and glycine dipeptides of porcine placenta ameliorate physical fatigue through enhancing dopaminergic systems". Molecular Medicine Reports 17.3 (2018): 4120-4130.
Chicago
Han, N., Kim, H., Kim, N., Lee, W., Jeong, H., Kim, H., Jeong, H."Leucine and glycine dipeptides of porcine placenta ameliorate physical fatigue through enhancing dopaminergic systems". Molecular Medicine Reports 17, no. 3 (2018): 4120-4130. https://doi.org/10.3892/mmr.2017.8335