Synergism Effects of Ursolic Acid Supplementation on the Levels of Irisin, C-reactive Protein, IL-6, and TNF-α During High-intensity Resistance Training in Low Activity Men

Author(s): Ehsan Asghari, Amir Rashidlamir*, Seyyed R.A. Hosseini, Mahtab Moazzami, Saeed Samarghandian, Tahereh Farkhondeh

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets
Formerly Current Drug Targets - Cardiovascular & Hematological Disorders

Volume 20 , Issue 2 , 2020

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Graphical Abstract:


Background: Ursolic Acid (UA) is a pentacyclic triterpenoid carboxylic acid which is extracted from plants. UA may enhance the effect of Resistance Training (RT) in human.

Objective: Current research was designed to show the effect of High-Intensity Resistance Training (HIRT) in the presence or absence of UA on the serum levels of irisin, CRP, IL-6 and TNF-α in the low activity men.

Methods: The study included twenty-two healthy male HIRT with placebo, supplementation, and HIRT in the presence of UA supplementation. The two groups received eight-week intervention including 2 sets of 8 exercises, with 8~10 repetitions at 70~75% of 1 repetition maximum and a 2 min rest interval between sets, performed 3 times/week. Placebo or UA orally was evaluated as 1 capsule 3 times/day during 8 weeks. The subsequent factors were measured post- and preintervention: C-Reactive Protein (CRP), Irisin, Tumor Necrotic Factor (TNF-α) and Interleukin-6 (IL-6).

Results: UA supplementation significantly increased the plasma levels of irisin in the HIRT+UA group versus the HIRT+P group (p<0.05). UA treatment also dramatically decreased the plasma levels of CRP, IL-6, and TNF-α in the HIRT+UA group versus the HIRT+P group (p<0.05).

Conclusion: The current data showed that UA-induced an increase in serum irisin and reduction of CRP, IL-6, and TNF-α may have beneficial effects as a chemical for increasing of the effects of HIRT in low activity men.

Keywords: Ursolic acid, Irisin, C-reactive protein, IL-6, TNF-α, resistance training.

Greenberg, A.S.; Obin, M.S. Obesity and the role of adipose tissue in inflammation and metabolism. Am. J. Clin. Nutr., 2006, 83(2), 461S-465S.
[] [PMID: 16470013]
Tartibian, B.; Azadpoor, N.; Abbasi, A. Effects of two different type of treadmill running on human blood leukocyte populations and inflammatory indices in young untrained men. J. Sports Med. Phys. Fitness, 2009, 49(2), 214-223.
[PMID: 19528902]
Dunstan, D. Diabetes: exercise and T2DM-move muscles more often! Nat. Rev. Endocrinol., 2011, 7(4), 189-190.
[] [PMID: 21427770]
Jakicic, J.M.; Davis, K.K. Obesity and physical activity. Psychiatr. Clin. North Am., 2011, 34(4), 829-840.
[] [PMID: 22098807]
Fukushima1, Y; Kurose, S; Shinno, H.; Thi Thu, H.C.; Takao, N.; Tsutsumi, H.; Hasegawa, T.; Nakajima, T.; Kimura, Y. Effects of body weight reduction on serum irisin and metabolic parameters in obese subjects. Diabetes Metab. J., 2016, 40, 386-395.
Hills, A.P.; Andersen, L.B.; Byrne, N.M. Physical activity and obesity in children. Br. J. Sports Med., 2011, 45(11), 866-870.
[] [PMID: 21836171]
Bozaoglu, K.; Bolton, K.; McMillan, J.; Zimmet, P.; Jowett, J.; Collier, G.; Walder, K.; Segal, D. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology, 2007, 148(10), 4687-4694.
[] [PMID: 17640997]
Ernst, M.C.; Sinal, C.J. Chemerin: at the crossroads of inflammation and obesity. Trends Endocrinol. Metab., 2010, 21(11), 660-667.
[] [PMID: 20817486]
Wrann, C.D.; White, J.P.; Salogiannnis, J.; Laznik-Bogoslavski, D.; Wu, J.; Ma, D.; Lin, J.D.; Greenberg, M.E.; Spiegelman, B.M. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab., 2013, 18(5), 649-659.
[] [PMID: 24120943]
Raschke, S.; Elsen, M.; Gassenhuber, H.; Sommerfeld, M.; Schwahn, U.; Brockmann, B.; Jung, R.; Wisløff, U.; Tjønna, A.E.; Raastad, T.; Hallén, J.; Norheim, F.; Drevon, C.A.; Romacho, T.; Eckardt, K.; Eckel, J. Evidence against a beneficial effect of irisin in humans. PLoS One, 2013, 8(9)e73680
[] [PMID: 24040023]
Norheim, F.; Langleite, T.M.; Hjorth, M.; Holen, T.; Kielland, A.; Stadheim, H.K.; Gulseth, H.L.; Birkeland, K.I.; Jensen, J.; Drevon, C.A. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J., 2014, 281(3), 739-749.
[] [PMID: 24237962]
Liu, J. Irisin as an exercise-stimulated hormone binding crosstalk between organs. Eur. Rev. Med. Pharmacol. Sci., 2015, 19(2), 316-321.
[PMID: 25683949]
Kurdiova, T.; Balaz, M.; Vician, M.; Maderova, D.; Vlcek, M.; Valkovic, L.; Srbecky, M.; Imrich, R.; Kyselovicova, O.; Belan, V.; Jelok, I.; Wolfrum, C.; Klimes, I.; Krssak, M.; Zemkova, E.; Gasperikova, D.; Ukropec, J.; Ukropcova, B. Effects of obesity, diabetes and exercise on Fndc5 gene expression and irisin release in human skeletal muscle and adipose tissue: in vivo and in vitro studies. J. Physiol., 2014, 592(5), 1091-1107.
[] [PMID: 24297848]
Brenmoehl, J.; Albrecht, E.; Komolka, K.; Schering, L.; Langhammer, M.; Hoeflich, A.; Maak, S. Irisin is elevated in skeletal muscle and serum of mice immediately after acute exercise. Int. J. Biol. Sci., 2014, 10(3), 338-349.
[] [PMID: 24644429]
Pedersen, B.K.; Akerström, T.C.A.; Nielsen, A.R.; Fischer, C.P. Role of myokines in exercise and metabolism. J. Appl. Physiol., 2007, 103(3), 1093-1098.
[] [PMID: 17347387]
Pekkala, S.; Wiklund, P.K.; Hulmi, J.J.; Ahtiainen, J.P.; Horttanainen, M.; Pöllänen, E.; Mäkelä, K.A.; Kainulainen, H.; Häkkinen, K.; Nyman, K.; Alén, M.; Herzig, K.H.; Cheng, S. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? J. Physiol., 2013, 591(21), 5393-5400.
[] [PMID: 24000180]
Handschin, C.; Spiegelman, B.M. The role of exercise and PGC1alpha in inflammation and chronic disease. Nature, 2008, 454(7203), 463-469.
[] [PMID: 18650917]
Löffler, D.; Müller, U.; Scheuermann, K.; Friebe, D.; Gesing, J.; Bielitz, J.; Erbs, S.; Landgraf, K.; Wagner, I.V.; Kiess, W.; Körner, A. Serum irisin levels are regulated by acute strenuous exercise. J. Clin. Endocrinol. Metab., 2015, 100(4), 1289-1299.
[] [PMID: 25625801]
Boström, P.; Wu, J.; Jedrychowski, M.P.; Korde, A.; Ye, L.; Lo, J.C.A.; Rasbach, K.A.; Boström, E.A.; Choi, J.H.; Long, J.Z.; Kajimura, S.; Zingaretti, M.C.; Vind, B.F.; Tu, H.; Cinti, S.; Højlund, K.; Gygi, S.P.; Spiegelman, B.M.A. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature, 2012, 481(7382), 463-468.
[] [PMID: 22237023]
Choi, Y.K.; Kim, M.K.; Bae, K.H.; Seo, H.A.; Jeong, J.Y.; Lee, W.K.; Kim, J.G.; Lee, I.K.; Park, K.G. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res. Clin. Pract., 2013, 100(1), 96-101.
[] [PMID: 23369227]
Huh, J.Y.; Panagiotou, G.; Mougios, V.; Brinkoetter, M.; Vamvini, M.T.; Schneider, B.E.; Mantzoros, C.S. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism, 2012, 61(12), 1725-1738.
[] [PMID: 23018146]
Van Marken Lichtenbelt, W.D.; Vanhommerig, J.W.; Smulders, N.M.; Drossaerts, J.M.; Kemerink, G.J.; Bouvy, N.D. Cold-activated brown adipose tissue in healthy men. N. Engl. J. Med., 2009, 360(15), 1500-8.
Yan, B.; Shi, X.; Zhang, H.; Pan, L.; Ma, Z.; Liu, S.; Liu, Y.; Li, X.; Yang, S.; Li, Z. Association of serum irisin with metabolic syndrome in obese Chinese adults. PLoS One, 2014, 9(4)e94235
[] [PMID: 24709991]
Kim, S.H.; Hong, J.H.; Lee, Y.C. Ursolic acid, a potential PPARγ agonist, suppresses ovalbumin-induced airway inflammation and Penh by down-regulating IL-5, IL-13, and IL-17 in a mouse model of allergic asthma. Eur. J. Pharmacol., 2013, 701(1-3), 131-143.
[] [PMID: 23201068]
Kasapis, C.; Thompson, P.D. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J. Am. Coll. Cardiol., 2005, 45(10), 1563-1569.
[] [PMID: 15893167]
Donges, C.E.; Duffield, R.; Drinkwater, E.J. Effects of resistance or aerobic exercise training on interleukin-6, C-reactive protein, and body composition. Med. Sci. Sports Exerc., 2010, 42(2), 304-313.
[] [PMID: 20083961]
Matsushita, K.; Yatsuya, H.; Tamakoshi, K.; Wada, K.; Otsuka, R.; Zhang, H.; Sugiura, K.; Kondo, T.; Murohara, T.; Toyoshima, H. Inverse association between adiponectin and C-reactive protein in substantially healthy Japanese men. Atherosclerosis, 2006, 188(1), 184-189.
[] [PMID: 16325822]
Bang, H.S.; Seo, D.Y.; Chung, Y.M.; Oh, K.M.; Park, J.J.; Arturo, F.; Jeong, S.H.; 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(5), 441-446.
[] [PMID: 25352765]
Ogasawara, R.; Sato, K.; Higashida, K.; Nakazato, K.; Fujita, S. Ursolic acid stimulates mTORC1 signaling after resistance exercise in rat skeletal muscle. Am. J. Physiol. Endocrinol. Metab., 2013, 305(6), E760-E765.
[] [PMID: 23900420]
Katashima, CK.; Silva, VR.; Gomes, T.L.; Pichard, C.; Pimentel, G.D. Ursolic acid and mechanisms of actions on adipose and muscle tissue: a systematic review. Obes. Rev., 2017, 18(6), 700-711.
Harriss, D.J.; Atkinson, G. International Journal of Sports Medicine - ethical standards in sport and exercise science research. Int. J. Sports Med., 2009, 30(10), 701-702.
[] [PMID: 19809942]
Kunkel, S.D.; Elmore, C.J.; Bongers, K.S.; Ebert, S.M.; Fox, D.K.; Dyle, M.C.; Bullard, S.A.; Adams, C.M. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease. PLoS One, 2012, 7(6)e39332
[] [PMID: 22745735]
Penninx, B.W.; Kritchevsky, S.B.; Newman, A.B.; Nicklas, B.J.; Simonsick, E.M.; Rubin, S.; Nevitt, M.; Visser, M.; Harris, T.; Pahor, M. Inflammatory markers and incident mobility limitation in the elderly. J. Am. Geriatr. Soc., 2004, 52(7), 1105-1113.[PubMed: 15209648].
[] [PMID: 15209648]
Phillips, M.D.; Flynn, M.G.; McFarlin, B.K.; Stewart, L.K.; Timmerman, K.L. Resistance training at eight-repetition maximum reduces the inflammatory milieu in elderly women. Med. Sci. Sports Exerc., 2010, 42(2), 314-325.
[] [PMID: 19927028]
Kaewthawee, N.; Brimson, S. The effects of ursolic acid on cytokine production via the MAPK pathways in leukemic T-cells. 2013. 12, 102-114
Petersen, A.M.W.; Pedersen, B.K. The anti-inflammatory effect of exercise. J. Appl. Physiol., 2005, 98(4), 1154-1162.
[] [PMID: 15772055]
Kelly, D.P. Medicine. Irisin, light my fire. Science, 2012, 336(6077), 42-43.
[] [PMID: 22491843]
Jilani, K.; Abed, M.; Zelenak, C.; Lang, E.; Qadri, S.M.; Lang, F. Triggering of erythrocyte cell membrane scrambling by ursolic acid. J. Nat. Prod., 2011, 74(10), 2181-2186.
[] [PMID: 21923134]
Woźniak, Ł.; Skąpska, S.; Marszałek, K. Ursolic acid-A pentacyclic triterpenoid with a wide spectrum of pharmacological activities. Molecules, 2015, 20(11), 20614-20641.
[] [PMID: 26610440]
Lawrence, T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol., 2009, 1(6)a001651
[] [PMID: 20457564]

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Year: 2020
Page: [138 - 144]
Pages: 7
DOI: 10.2174/1871529X19666190918144727
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