Abstract
Purpose
Delayed-onset muscle soreness (DOMS) describes an entity characterized by ultrastructural muscle damage. Hesperidin methyl chalcone (HMC) is a synthetic flavonoid presenting analgesic, anti-inflammatory, and antioxidant properties. We evaluated the effects of HMC upon DOMS.
Method
In a preventive paradigm, 31 sedentary young men were submitted to a randomized, double-blinded parallel trial and received HMC 500 mg or one placebo capsule × 3 days before an intense dynamic exercise protocol (concentric/eccentric actions) applied for lower limbs for inducing muscle damage. Assessments were conducted at baseline, and 24 and 48 h after, comprising physical performance, and post-muscle soreness and damage, inflammation, recovery of muscle strength, and postural balance associated with DOMS. HMC safety was also evaluated. Thirty participants completed the study.
Results
HMC improved the performance of participants during exercise (40.3 vs 51.3 repetitions to failure, p = 0.0187) and inhibited CPK levels (90.5 vs 57.9 U/L, p = 0.0391) and muscle soreness during passive quadriceps palpation (2.6 vs 1.4 VAS cm, p = 0.0439), but not during active actions, nor did it inhibit IL-1β or IL-10 levels. HMC improved muscle strength recovery, and satisfactorily refined postural balance, without inducing injury to kidneys or liver.
Conclusions
Preemptive HMC supplementation may be beneficial for boosting physical performance and for the amelioration of clinical parameters related to DOMS, including pain on muscle palpation, increased blood CPK levels, and muscle strength and proprioceptive deficits, without causing adverse effects. These data advance the understanding of the benefits provided by HMC for DOMS treatment, which supports its usefulness for such purpose.
Similar content being viewed by others
Data availability
The data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Abbreviations
- 1RM:
-
One-maximum repetition
- ANOVA:
-
Analysis of variance
- AP:
-
Anteroposterior
- ATP:
-
Adenosine triphosphate
- BMI:
-
Body mass index
- COP:
-
Center-of-pressure
- CPK:
-
Creatine phosphokinase
- DOMS:
-
Delayed-onset muscle soreness
- EDTA:
-
Ethylenediaminetetraacetic acid
- IDEP:
-
Intense dynamic exercise protocol
- EF:
-
Effect size
- ELISA:
-
Enzyme-linked immunosorbent assay
- EIMD:
-
Exercise-induced muscle damage
- GGT:
-
Gamma glutamyl transferase
- HMC:
-
Hesperidin methyl chalcone
- IL-1β:
-
Interleukin-1β
- IL-10:
-
Interleukin-10
- ML:
-
Mediolateral
- NFκB :
-
Nuclear factor κB
- NSAIDs:
-
Non-steroidal anti-inflammatory drugs
- PLA:
-
Placebo
- WHO:
-
World Health Organization
- VAS:
-
Visual analogue scale
References
Alvarez P, Bogen O, Green PG, Levine JD (2017) Nociceptor interleukin 10 receptor 1 is critical for muscle analgesia induced by repeated bouts of eccentric exercise in the rat. Pain 158(8):1481–1488. https://doi.org/10.1097/j.pain.0000000000000936
Ammar A, Turki M, Chtourou H, Hammouda O, Trabelsi K, Kallel C, Abdelkarim O, Hoekelmann A, Bouaziz M, Ayadi F, Driss T, Souissi N (2016) Pomegranate supplementation accelerates recovery of muscle damage and soreness and inflammatory markers after a weightlifting training session. PLoS ONE 11(10):e0160305. https://doi.org/10.1371/journal.pone.0160305
Aujla RS, Patel R (2022) Creatine Phosphokinase. In: StatPearls. Treasure Island (FL)
Bartley EJ, Fillingim RB (2013) Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth 111(1):52–58. https://doi.org/10.1093/bja/aet127
Biesemann N, Ried JS, Ding-Pfennigdorff D, Dietrich A, Rudolph C, Hahn S, Hennerici W, Asbrand C, Leeuw T, Strubing C (2018) High throughput screening of mitochondrial bioenergetics in human differentiated myotubes identifies novel enhancers of muscle performance in aged mice. Sci Rep 8(1):9408. https://doi.org/10.1038/s41598-018-27614-8
Borghi SM, Zarpelon AC, Pinho-Ribeiro FA, Cardoso RD, Cunha TM, Alves-Filho JC, Ferreira SH, Cunha FQ, Casagrande R, Verri WA Jr (2014) Targeting interleukin-1beta reduces intense acute swimming-induced muscle mechanical hyperalgesia in mice. J Pharm Pharmacol 66(7):1009–1020. https://doi.org/10.1111/jphp.12226
Borghi SM, Pinho-Ribeiro FA, Zarpelon AC, Cunha TM, Alves-Filho JC, Ferreira SH, Cunha FQ, Casagrande R, Verri WA Jr (2015) Interleukin-10 limits intense acute swimming-induced muscle mechanical hyperalgesia in mice. Exp Physiol. https://doi.org/10.1113/EP085026
Bowtell JL, Sumners DP, Dyer A, Fox P, Mileva KN (2011) Montmorency cherry juice reduces muscle damage caused by intensive strength exercise. Med Sci Sports Exerc 43(8):1544–1551. https://doi.org/10.1249/MSS.0b013e31820e5adc
Boyle P, Diehm C, Robertson C (2003) Meta-analysis of clinical trials of Cyclo 3 Fort in the treatment of chronic venous insufficiency. Int Angiol 22(3):250–262
Bussmann AJC, Zaninelli TH, Saraiva-Santos T, Fattori V, Guazelli CFS, Bertozzi MM, Andrade KC, Ferraz CR, Camilios-Neto D, Casella AMB, Casagrande R, Borghi SM, Verri WA Jr (2022) The flavonoid hesperidin methyl chalcone targets cytokines and oxidative stress to reduce diclofenac-induced acute renal injury: contribution of the Nrf2 redox-sensitive pathway. Antioxidants (basel). https://doi.org/10.3390/antiox11071261
Bussulo SKD, Ferraz CR, Carvalho TT, Verri WA Jr, Borghi SM (2021) Redox interactions of immune cells and muscle in the regulation of exercise-induced pain and analgesia: implications on the modulation of muscle nociceptor sensory neurons. Free Radic Res 55(7):757–775. https://doi.org/10.1080/10715762.2021.1953696
Cannon JG, Fielding RA, Fiatarone MA, Orencole SF, Dinarello CA, Evans WJ (1989) Increased interleukin 1 beta in human skeletal muscle after exercise. Am J Physiol 257(2 Pt 2):R451-455. https://doi.org/10.1152/ajpregu.1989.257.2.R451
Cerqueira E, Marinho DA, Neiva HP, Lourenco O (2019) Inflammatory effects of high and moderate intensity exercise—a systematic review. Front Physiol 10:1550. https://doi.org/10.3389/fphys.2019.01550
Chanal JL, Cousse H, Sicart MT, Bonnaud B, Marignan R (1981) Absorption and elimination of (14C) hesperidin methylchalcone in the rat. Eur J Drug Metab Pharmacokinet 6(3):171–177. https://doi.org/10.1007/BF03189486
Chen TC, Yang TJ, Huang MJ, Wang HS, Tseng KW, Chen HL, Nosaka K (2019) Damage and the repeated bout effect of arm, leg, and trunk muscles induced by eccentric resistance exercises. Scand J Med Sci Sports 29(5):725–735. https://doi.org/10.1111/sms.13388
Cheung K, Hume P, Maxwell L (2003) Delayed onset muscle soreness: treatment strategies and performance factors. Sports Med 33(2):145–164
Cohen J (1992) A power primer. Psychol Bull 112(1):155–159. https://doi.org/10.1037//0033-2909.112.1.155
Crowther F, Sealey R, Crowe M, Edwards A, Halson S (2017) Influence of recovery strategies upon performance and perceptions following fatiguing exercise: a randomized controlled trial. BMC Sports Sci Med Rehabil 9:25. https://doi.org/10.1186/s13102-017-0087-8
da Silva W, Machado AS, Souza MA, Mello-Carpes PB, Carpes FP (2018) Effect of green tea extract supplementation on exercise-induced delayed onset muscle soreness and muscular damage. Physiol Behav 194:77–82. https://doi.org/10.1016/j.physbeh.2018.05.006
Damsgard E, Thrane G, Anke A, Fors T, Roe C (2010) Activity-related pain in patients with chronic musculoskeletal disorders. Disabil Rehabil 32(17):1428–1437. https://doi.org/10.3109/09638280903567877
Dupuy O, Douzi W, Theurot D, Bosquet L, Dugue B (2018) An evidence-based approach for choosing post-exercise recovery techniques to reduce markers of muscle damage, soreness, fatigue, and inflammation: a systematic review with meta-analysis. Front Physiol 9:403. https://doi.org/10.3389/fphys.2018.00403
Eker Y, Belgen Kaygisiz B (2021) The effect of pain severity on balance, postural stability and fall risk in patients with shoulder pathologies. Arch Med Sci 17(2):390–396. https://doi.org/10.5114/aoms.2020.94491
Faria FR, Gomes AC, Antunes A, Rezende KR, Pimentel GD, Oliveira CLP, Antunes BM, Lira FS, Aoki MS, Mota JF (2020) Effects of turmeric extract supplementation on inflammation and muscle damage after a half-marathon race: a randomized, double-blind, placebo-controlled trial. Eur J Appl Physiol 120(7):1531–1540. https://doi.org/10.1007/s00421-020-04385-7
Ferraz CR, Carvalho TT, Manchope MF, Artero NA, Rasquel-Oliveira FS, Fattori V, Casagrande R, Verri WA Jr (2020) Therapeutic potential of flavonoids in pain and inflammation: mechanisms of action, pre-clinical and clinical data, and pharmaceutical development. Molecules. https://doi.org/10.3390/molecules25030762
Ghlichloo I, Gerriets V (2022) Nonsteroidal anti-inflammatory drugs (NSAIDs). In: StatPearls. Treasure Island (FL)
Granacher U, Muehlbauer T, Gruber M (2012) A qualitative review of balance and strength performance in healthy older adults: impact for testing and training. J Aging Res 2012:708905. https://doi.org/10.1155/2012/708905
Hannestad J, DellaGioia N, Bloch M (2011) The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36(12):2452–2459. https://doi.org/10.1038/npp.2011.132
Hassan BS, Mockett S, Doherty M (2001) Static postural sway, proprioception, and maximal voluntary quadriceps contraction in patients with knee osteoarthritis and normal control subjects. Ann Rheum Dis 60(6):612–618. https://doi.org/10.1136/ard.60.6.612
Heiss R, Lutter C, Freiwald J, Hoppe MW, Grim C, Poettgen K, Forst R, Bloch W, Huttel M, Hotfiel T (2019) Advances in delayed-onset muscle soreness (DOMS)—Part II: treatment and prevention. Sportverletz Sportschaden 33(1):21–29. https://doi.org/10.1055/a-0810-3516
Hotfiel T, Freiwald J, Hoppe MW, Lutter C, Forst R, Grim C, Bloch W, Huttel M, Heiss R (2018) Advances in delayed-onset muscle soreness (DOMS): part I: pathogenesis and diagnostics. Sportverletz Sportschaden 32(4):243–250. https://doi.org/10.1055/a-0753-1884
Huang CC, Lee MC, Ho CS, Hsu YJ, Ho CC, Kan NW (2021) Protective and recovery effects of resveratrol supplementation on exercise performance and muscle damage following acute plyometric exercise. Nutrients. https://doi.org/10.3390/nu13093217
Imperatrice M, Cuijpers I, Troost FJ, Sthijns M (2022) Hesperidin functions as an ergogenic aid by increasing endothelial function and decreasing exercise-induced oxidative stress and inflammation, thereby contributing to improved exercise performance. Nutrients. https://doi.org/10.3390/nu14142955
Jajtner AR, Hoffman JR, Townsend JR, Beyer KS, Varanoske AN, Church DD, Oliveira LP, Herrlinger KA, Radom-Aizik S, Fukuda DH, Stout JR (2016) The effect of polyphenols on cytokine and granulocyte response to resistance exercise. Physiol Rep. https://doi.org/10.1481/phy2.13058
Kunutsor SK (2016) Gamma-glutamyltransferase-friend or foe within? Liver Int 36(12):1723–1734. https://doi.org/10.1111/liv.13221
Landmark T, Romundstad P, Borchgrevink PC, Kaasa S, Dale O (2011) Associations between recreational exercise and chronic pain in the general population: evidence from the HUNT 3 study. Pain 152(10):2241–2247. https://doi.org/10.1016/j.pain.2011.04.029
Lannersten L, Kosek E (2010) Dysfunction of endogenous pain inhibition during exercise with painful muscles in patients with shoulder myalgia and fibromyalgia. Pain 151(1):77–86. https://doi.org/10.1016/j.pain.2010.06.021
Lara AJ, Abian J, Alegre LM, Jimenez L, Aguado X (2006) Assessment of power output in jump tests for applicants to a sports sciences degree. J Sports Med Phys Fitness 46(3):419–424
Lima LV, Abner TSS, Sluka KA (2017) Does exercise increase or decrease pain? Central mechanisms underlying these two phenomena. J Physiol 595(13):4141–4150. https://doi.org/10.1113/JP273355
Littlewood C, Mawson S, May S, Walters S (2015) Understanding the barriers and enablers to implementation of a self-managed exercise intervention: a qualitative study. Physiotherapy 101(3):279–285. https://doi.org/10.1016/j.physio.2015.01.001
Liu S, Liu K, Wang Y, Wu C, Xiao Y, Liu S, Yu J, Ma Z, Liang H, Li X, Li Y, Zhou L (2022) Hesperidin methyl chalcone ameliorates lipid metabolic disorders by activating lipase activity and increasing energy metabolism. Biochim Biophys Acta Mol Basis Dis 1869(2):166620. https://doi.org/10.1016/j.bbadis.2022.166620
MacIntyre DL, Reid WD, McKenzie DC (1995) Delayed muscle soreness. The inflammatory response to muscle injury and its clinical implications. Sports Med 20(1):24–40. https://doi.org/10.2165/00007256-199520010-00003
Martinez N, Campbell B, Franek M, Buchanan L, Colquhoun R (2016a) The effect of acute pre-workout supplementation on power and strength performance. J Int Soc Sports Nutr 13:29. https://doi.org/10.1186/s12970-016-0138-7
Martinez RM, Pinho-Ribeiro FA, Steffen VS, Caviglione CV, Pala D, Baracat MM, Georgetti SR, Verri WA, Casagrande R (2016b) Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative stress and inflammation induced by ultraviolet B irradiation. Photochem Photobiol Sci 15(4):554–563. https://doi.org/10.1039/c5pp00467e
Martinez-Noguera FJ, Marin-Pagan C, Carlos-Vivas J, Alcaraz PE (2020) Effects of 8 weeks of 2S-hesperidin supplementation on performance in amateur cyclists. Nutrients. https://doi.org/10.3390/nu12123911
Martinez-Noguera FJ, Marin-Pagan C, Carlos-Vivas J, Alcaraz PE (2021) 8-week supplementation of 2S-hesperidin modulates antioxidant and inflammatory status after exercise until exhaustion in amateur cyclists. Antioxidants (basel). https://doi.org/10.3390/antiox10030432
Mense S (1993) Peripheral mechaniism of muscle nociception and local muscle pain. J Musculoskeletal Pain 1(1):133–170. https://doi.org/10.1300/J094v01n01_10
Merkle SL, Sluka KA, Frey-Law LA (2020) The interaction between pain and movement. J Hand Ther 33(1):60–66. https://doi.org/10.1016/j.jht.2018.05.001
Moir G (2008) Three different methods of calculating vertical jump height from force platform data in men and women. Measur Phys Educ Exerc Sci 12(4):207–218. https://doi.org/10.1080/10913670802349766
Monjotin N, Tenca G (2022) Lymphotonic activity of Ruscus extract, hesperidin methyl chalcone and vitamin C in human lymphatic smooth muscle cells. Microvasc Res 139:104274. https://doi.org/10.1016/j.mvr.2021.104274
Morgan PT, Wollman PM, Jackman SR, Bowtell JL (2018) Flavanol-Rich Cacao Mucilage juice enhances recovery of power but not strength from intensive exercise in healthy, Young Men. Sports (basel). https://doi.org/10.3390/sports6040159
Nicol LM, Rowlands DS, Fazakerly R, Kellett J (2015) Curcumin supplementation likely attenuates delayed onset muscle soreness (DOMS). Eur J Appl Physiol 115(8):1769–1777. https://doi.org/10.1007/s00421-015-3152-6
Nosaka K, Newton M, Sacco P (2002) Delayed-onset muscle soreness does not reflect the magnitude of eccentric exercise-induced muscle damage. Scand J Med Sci Sports 12(6):337–346. https://doi.org/10.1034/j.1600-0838.2002.10178.x
Ohrbach R, Gale EN (1989) Pressure pain thresholds, clinical assessment, and differential diagnosis: reliability and validity in patients with myogenic pain. Pain 39(2):157–169. https://doi.org/10.1016/0304-3959(89)90003-1
Pedersen BK, Saltin B (2015) Exercise as medicine—evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports 25(Suppl 3):1–72. https://doi.org/10.1111/sms.12581
Pinho-Ribeiro FA, Hohmann MS, Borghi SM, Zarpelon AC, Guazelli CF, Manchope MF, Casagrande R, Verri WA Jr (2015) Protective effects of the flavonoid hesperidin methyl chalcone in inflammation and pain in mice: role of TRPV1, oxidative stress, cytokines and NF-kappaB. Chem Biol Interact 228:88–99. https://doi.org/10.1016/j.cbi.2015.01.011
Proske U, Morgan DL (2001) Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications. J Physiol 537(Pt 2):333–345. https://doi.org/10.1111/j.1469-7793.2001.00333.x
Rasquel-Oliveira FS, Manchope MF, Staurengo-Ferrari L, Ferraz CR, Saraiva-Santos T, Zaninelli TH, Fattori V, Artero NA, Badaro-Garcia S, de Freitas A, Casagrande R, Verri WA, Jr. (2020) Hesperidin methyl chalcone interacts with NFkappaB Ser276 and inhibits zymosan-induced joint pain and inflammation, and RAW 264.7 macrophage activation. Inflammopharmacology 28 (4):979–992. https://doi.org/10.1007/s10787-020-00686-7
Robertson RJ, Goss FL, Rutkowski J, Lenz B, Dixon C, Timmer J, Frazee K, Dube J, Andreacci J (2003) Concurrent validation of the OMNI perceived exertion scale for resistance exercise. Med Sci Sports Exerc 35(2):333–341. https://doi.org/10.1249/01.MSS.0000048831.15016.2A
Rodrigues CP, Jacinto JL, Roveratti MC, Merlo JK, Soares-Caldeira LF, Silva Ribeiro A, Nunes JP, Junior EO, Aguiar AF (2022) Effects of photobiomodulation/laser therapy combined with resistance training on quadriceps hypertrophy and strength, and postural balance in older women: a randomized, triple-blinded, placebo-controlled study. J Geriatr Phys Ther 45(3):125–133. https://doi.org/10.1519/JPT.0000000000000313
Roveratti MC, Jacinto JL, Oliveira DB, da Silva RA, Andraus RAC, de Oliveira EP, Ribeiro AS, Aguiar AF (2019) Effects of beta-alanine supplementation on muscle function during recovery from resistance exercise in young adults. Amino Acids 51(4):589–597. https://doi.org/10.1007/s00726-018-02686-y
Ruhe A, Fejer R, Walker B (2011) Is there a relationship between pain intensity and postural sway in patients with non-specific low back pain? BMC Musculoskelet Disord 12:162. https://doi.org/10.1186/1471-2474-12-162
Ruiz-Miyazawa KW, Pinho-Ribeiro FA, Borghi SM, Staurengo-Ferrari L, Fattori V, Amaral FA, Teixeira MM, Alves-Filho JC, Cunha TM, Cunha FQ, Casagrande R, Verri WA Jr (2018) Hesperidin methylchalcone suppresses experimental gout arthritis in mice by inhibiting NF-kappaB activation. J Agric Food Chem 66(25):6269–6280. https://doi.org/10.1021/acs.jafc.8b00959
Scallan J, Huxley VH, Korthuis RJ (2010) Capillary fluid exchange: regulation, functions, and pathology. integrated systems physiology: from molecule to function to disease. San Rafael (CA)
Schoenfeld BJ (2012) The use of nonsteroidal anti-inflammatory drugs for exercise-induced muscle damage: implications for skeletal muscle development. Sports Med 42(12):1017–1028. https://doi.org/10.1007/BF03262309
Sluka KA, Frey-Law L, Hoeger Bement M (2018) Exercise-induced pain and analgesia? Underlying mechanisms and clinical translation. Pain 159(Suppl 1):S91–S97. https://doi.org/10.1097/j.pain.0000000000001235
Smith BE, Hendrick P, Bateman M, Holden S, Littlewood C, Smith TO, Logan P (2019) Musculoskeletal pain and exercise-challenging existing paradigms and introducing new. Br J Sports Med 53(14):907–912. https://doi.org/10.1136/bjsports-2017-098983
Verri WA Jr, Cunha TM, Parada CA, Poole S, Cunha FQ, Ferreira SH (2006) Hypernociceptive role of cytokines and chemokines: targets for analgesic drug development? Pharmacol Ther 112(1):116–138. https://doi.org/10.1016/j.pharmthera.2006.04.001
WHO (2020) World Health Organization Physical activity:https://www.who.int/news-room/fact-sheets/detail/physical-activity.
Wiesenfeld-Hallin Z (2005) Sex differences in pain perception. Gend Med 2(3):137–145. https://doi.org/10.1016/s1550-8579(05)80042-7
Funding
This work was supported by grants from Fundação Nacional de Desenvolvimento do Ensino Superior Particular (FUNADESP; Grant No. 5301159) research fellowship and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) senior research fellowship (309633/2021-4). THZ and TSS received CAPES PhD bursary (finance code 001).
Author information
Authors and Affiliations
Contributions
MZL, AFA, AKSA, THZ, OKH, TSS, MMB, NAS, EOJ, WAVJ, and SMB conducted data acquisition, analysis, and interpretations. AFA, OKH, EOJ, and WAVJ contributed with reagents, analytical tools, and expert intellectual support for the study. SMB conceived and designed the study and supervised the project. MZL, WAVJ, and SMB wrote and critically revised the manuscript. All authors contributed to the content, critical review, and approved the final version of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflicts of interest.
Additional information
Communicated by Michael I Lindinger.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Luque, M.Z., Aguiar, A.F., da Silva-Araújo, A.K. et al. Evaluation of a preemptive intervention regimen with hesperidin methyl chalcone in delayed-onset muscle soreness in young adults: a randomized, double-blinded, and placebo-controlled trial study. Eur J Appl Physiol 123, 1949–1964 (2023). https://doi.org/10.1007/s00421-023-05207-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00421-023-05207-2