A synergistic blend of Garcinia mangostana fruit rind and Cinnamomum tamala leaf extracts enhances myogenic differentiation and mitochondrial biogenesis in vitro and muscle growth and strength in mice

  • Swaraj Sinha Department of Cell and Molecular Biology, Laila Nutraceuticals R&D Center, Vijayawada, Andhra Pradesh, India https://orcid.org/0009-0001-8842-3344
  • Krishnaraju Venkata Alluri Department of Pharmacology and Clinical Research, Laila Nutraceuticals R&D Center, Vijayawada, Andhra Pradesh, India https://orcid.org/0000-0002-0550-7164
  • Venkateswarlu Somepalli Department of Phytochemistry, Laila Nutraceuticals R&D Center, Vijayawada, Andhra Pradesh, India https://orcid.org/0000-0002-4625-6277
  • Trimurtulu Golakoti Department of Phytochemistry, Laila Nutraceuticals R&D Center, Vijayawada, Andhra Pradesh, India https://orcid.org/0000-0002-2358-565X
  • Krishanu Sengupta Department of Cell and Molecular Biology, Laila Nutraceuticals R&D Center, Vijayawada, Andhra Pradesh, India
Keywords: Ergogenic phytonutrients;, mammalian target of rapamycin (mTOR), mitochondrial biogenesis, muscle growth and strength, nitric oxide

Abstract

Background: A proprietary combination of Garcinia mangostana fruit rind and Cinnamomum tamala leaf extracts (LI80020F4, CinDura®) improved the physical performance and muscle strength of resistance-trained adult males.

Objective: This study assessed the underlying mechanisms of the ergogenic potential of LI80020F4 in in vitro and in vivo models.

Methods: The individual extracts and their combination (LI80020F4) were assessed for nitrite production in EAhy926 human endothelial cells. Subsequent experiments evaluated the effect of LI80020F4 in myotube formation in C2C12 mouse myoblasts, expression of mammalian target of rapamycin (mTOR) signaling proteins, myogenic factors, and mitochondrial functions in L6 rat myoblasts.

Moreover, adult male ICR mice were randomly assigned (n = 15) into vehicle control (G1), exercise alone (G2), oxymetholone-16 mg/kg body weight (bw) (G3), and 75 (G4)-, 150 (G5)-, or 300 (G6) mg/kg bw of LI80020F4, orally gavaged for 28 days. G1 and G2 mice received 0.5% carboxymethylcellulose sodium. Following completion, muscle strength and physical performance were assessed on forelimb grip strength and forced swimming test (FST), respectively. Gastrocnemius (GA), tibialis anterior (TA) muscle weights, muscle fiber cross-sectional area (CSA), levels of muscle, and serum protein markers were also determined.

Results: LI80020F4 increased nitrite production in EAhy926 cells in a dose-dependent manner. LI80020F4 induced C2C12 myotube formation, increased mitochondrial biogenesis, upregulated the expressions of activated mTOR and other mitochondria and myogenic proteins, and mitigated H2O2-induced mitochondrial membrane depolarization in the myoblast cells. In the animal study, 75, 150, and 300 mg/kg bw LI80020F4 doses significantly (P < 0.05) increased the animals’ forelimb grip strength. Mid- and high-dose groups showed increased swimming time, increased muscle weight, CSA, muscle growth-related, and mitochondrial protein expressions in the GA muscles.

Conclusion: LI80020F4 increases nitric oxide production in the endothelial cells, mitochondrial biogenesis and function, upregulates skeletal muscle growth-related protein expressions and reduces oxidative stress; together, it explains the basis of the ergogenic potential of LI80020F4.

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References


1.
Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr 2000; 72(2 Suppl): 624S–36S. doi: 10.1093/ajcn/72.2.624S


2.
Sellami M, Slimeni O, Pokrywka A, Kuvačić G, D Hayes L, Milic M, et al. Herbal medicine for sports: a review. J Int Soc Sports Nutr 2018; 15: 14. doi: 10.1186/s12970-018-0218-y


3.
Williams M. Dietary supplements and sports performance: herbals. J Int Soc Sports Nutr 2006; 3: 1. doi: 10.1186/1550-2783-3-1-1


4.
Garcia JF, Arribalzaga S, Díez R, Lopez C, Fernandez MN, Garcia JJ, et al. Herbs as an active ingredient in sport: availability and information on the internet. Nutrients 2022; 14(13): 2764. doi: 10.3390/nu14132764


5.
Amir M, Vohra M, Raj RG, Osoro I, Sharma A. Adaptogenic herbs: a natural way to improve athletic performance. Health Sci Rev 2023; 7: 100092. doi: 10.1016/j.hsr.2023.100092


6.
Vårvik FT, Bjørnsen T, Gonzalez AM. Acute effect of citrulline malate on repetition performance during strength training: a systematic review and meta-analysis. Int J Sport Nutr Exerc Metab 2021; 31(4): 350–8. doi: 10.1123/ijsnem.2020-0295


7.
Bailey SJ, Vanhatalo A, Winyard PG, Jones AM. The nitrate-nitrite-nitric oxide pathway: its role in human exercise physiology. Eur J Sport Sci 2012; 12(4): 309–20. doi: 10.1080/17461391.2011.635705


8.
Archer SL, Huang JM, Hampl V, Nelson DP, Shultz PJ, Weir EK. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci USA 1994; 91(16): 7583–87. doi: 10.1073/pnas.91.16.7583


9.
Figueroa A, Jaime SJ, Morita M, Gonzales JU, Moinard C. L-citrulline supports vascular and muscular benefits of exercise training in older adults. Exerc Sport Sci Rev 2020; 48(3): 133–9. doi: 10.1249/JES.0000000000000223


10.
Cholewa J, Trexler E, Lima-Soares F, de Araújo Pessôa K, Sousa-Silva R, Santos AM, et al. Effects of dietary sports supplements on metabolite accumulation, vasodilation and cellular swelling in relation to muscle hypertrophy: a focus on ‘secondary’ physiological determinants. Nutrition 2019; 60: 241–51. doi: 10.1016/j.nut.2018.10.011


11.
Hood DA, Irrcher I, Ljubicic V, Joseph AM. Coordination of metabolic plasticity in skeletal muscle. J Exp Biol 2006; 209: 2265–75. doi: 10.1242/jeb.02182


12.
Dyakova EY, Kapilevich LV, Shylko VG, Popov SV, Anfinogenova Y. Physical exercise associated with NO production: signaling pathways and significance in health and disease. Front Cell Dev Biol 2015; 3: 19. doi: 10.3389/fcell.2015.00019


13.
Groennebaek T, Vissing K. Impact of resistance training on skeletal muscle mitochondrial biogenesis, content, and function. Front Physiol 2017; 8: 713. doi: 10.3389/fphys.2017.00713


14.
Campos HO, Drummond LR, Rodrigues QT, Machado FS, Pires W, Wanner SP, et al. Nitrate supplementation improves physical performance specifically in non-athletes during prolonged open-ended tests: a systematic review and meta-analysis. Br J Nutr 2018; 119: 636–57. doi: 10.1017/S0007114518000132


15.
Hughes DC, Ellefsen S, Baar K. Adaptations to endurance and strength training. Cold Spring Harb Perspect Med 2018; 8(6): a029769. doi: 10.1101/cshperspect.a029769


16.
Konda MR, Alluri KV, Janardhanan PK, Trimurtulu G, Sengupta K. Combined extracts of Garcinia mangostana fruit rind and Cinnamomum tamala leaf supplementation enhances muscle strength and endurance in resistance trained males. J Int Soc Sports Nutr 2018; 15(1): 50. doi: 10.1186/s12970-018-0257-4


17.
Ovalle-Magallanes B, Eugenio-Pérez D, Pedraza-Chaverri J. Medicinal properties of mangosteen (Garcinia mangostana L.): a comprehensive update. Food Chem Toxicol 2017; 109(Pt 1): 102–22. doi: 10.1016/j.fct.2017.08.021


18.
Ibrahim MY, Hashim NM, Mariod AA, Mohan S, Abdulla MA, Abdelwahab IS, et al. α-Mangostin from Garcinia mangostana Linn: an updated review of its pharmacological properties. Arab J Chem 2016; 9(3): 317–29. doi: 10.1016/j.arabjc.2014.02.011


19.
Sharma G, Nautiyal AR. Cinnamomum tamala: a valuable tree from Himalayas. Int J Med Arom Plants 2011; 1(1): 1–4.


20.
Tiwari S, Talreja S. Importance of Cinnamomum tamala in the treatment of various diseases. Pharmacogn J 2020; 12(6s): 1792–6. doi: 10.5530/pj.2020.12.241


21.
Pyakurel D, Jan HA, Kunwar RM, Bussmann RW, Paniagua-Zambrana NY. Cinnamomum tamala (Buch.-Ham.) T. Nees & Nees LAURACEAE. In: Kunwar RM, Sher H, Bussmann RW, eds. Ethnobotany of the Himalayas. Ethnobotany of mountain regions. Champaign, IL: Springer; 2021: 1–7. doi: 10.1007/978-3-030-45597-2_57-1


22.
Perelman A, Wachtel C, Cohen M, Haupt S, Shapiro H, Tzur A. JC-1: alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry. Cell Death Dis 2012; 3: e430. doi: 10.1038/cddis.2012.171


23.
Kundimi S, Kavungala KC, Sinha S, Tayi VNR, Kundurthi NR, Golakoti T, et al. Combined extracts of Moringa oleifera, Murraya koeingii leaves, and Curcuma longa rhizome increases energy expenditure and controls obesity in high-fat diet-fed rats. Lipids Health Dis 2020; 19: 198. doi: 10.1186/s12944-020-01376-7


24.
Charan J, Kantharia ND. How to calculate sample size in animal studies? J Pharmacol Pharmacother 2013; 4(4): 303–6. doi: 10.4103/0976-500X.119726


25.
Kislinger T, Gramolini AO, Pan Y, Rahman K, MacLennan DH, Emili A. Proteome dynamics during C2C12 myoblast differentiation. Mol Cell Proteomics 2005; 4(7): 887–901. doi: 10.1074/mcp.M400182-MCP200


26.
Moran JL, Li Y, Hill AA, Mounts WM, Miller CP. Gene expression changes during mouse skeletal myoblast differentiation revealed by transcriptional profiling. Physiol Genomics 2002; 10: 103–111. doi: 10.1152/physiolgenomics.00011.2002


27.
Lazure F, Blackburn DM, Corchado AH, Sahinyan K, Karam N, Sharanek A, et al. Myf6/MRF4 is a myogenic niche regulator required for the maintenance of the muscle stem cell pool. EMBO Rep 2020; 21(12): e49499. doi: 10.15252/embr.201949499


28.
Hernández-Hernández JM, García-González EG, Brun CE, Rudnicki MA. The myogenic regulatory factors, determinants of muscle development, cell identity and regeneration. Semin Cell Dev Biol 2017; 72: 10–18. doi: 10.1016/j.semcdb.2017.11.010


29.
Popov LD. Mitochondrial biogenesis: an update. J Cell Mol Med 2020; 24(9): 4892–99. doi: 10.1111/jcmm.15194


30.
Chaban Y, Boekema EJ, Dudkina NV. Structures of mitochondrial oxidative phosphorylation supercomplexes and mechanisms for their stabilisation. Biochim Biophys Acta 2014; 1837(4): 418–26. doi: 10.1016/j.bbabio.2013.10.004


31.
Jiang DJ, Dai Z, Li YJ. Pharmacological effects of xanthones as cardiovascular protective agents. Cardiovasc Drug Rev 2004; 22(2): 91–102. doi: 10.1111/j.1527-3466.2004.tb00133.x


32.
Serreli G, Deiana M. Role of dietary polyphenols in the activity and expression of nitric oxide synthases: a review. Antioxidants 2023; 12(1): 147. doi: 10.3390/antiox12010147


33.
Jiang M, Huang S, Duan W, Liu Q, Lei M. Alpha-mangostin improves endothelial dysfunction in db/db mice through inhibition of aSMase/ceramide pathway. J Cell Mol Med 2021; 25(7): 3601–9. doi: 10.1111/jcmm.16456


34.
Ugusman A, Zakaria Z, Chua KH, Nordin NA, Abdullah Mahdy Z. Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells. Sci World J 2014; 2014: 169370. doi: 10.1155/2014/169370


35.
Sibisi NC, Snyman C, Myburgh KH, Niesler CU. Evaluating the role of nitric oxide in myogenesis in vitro. Biochimie 2022; 196: 216–24. doi: 10.1016/j.biochi.2021.11.006


36.
Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, et al. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 2001; 3(11): 1009–13. doi: 10.1038/ncb1101-1009


37.
Gumucio JP, Mendias CL. Atrogin-1, MuRF-1, and sarcopenia. Endocrine 2013; 43(1): 12–21. doi: 10.1007/s12020-012-9751-7


38.
Taengthong P, Phoungpetchara I, Khongsombat O, Tunsophon S. Synergistic effects of curcumin and gamma-oryzanol solid dispersions ameliorate muscle atrophy by upregulating Nrf2 and IGF1/Insulin-Akt-mTOR activities in middle-aged rats. J Funct Foods 2022; 99: 105318. doi.org/10.1016/j.jff.2022.105318


39.
Tengan CH, Rodrigues GS, Godinho RO. Nitric oxide in skeletal muscle: role on mitochondrial biogenesis and function. Int J Mol Sci 2012; 13(12): 17160–84. doi: 10.3390/ijms131217160


40.
Vargas-Mendoza N, Angeles-Valencia M, Morales-González Á, Madrigal-Santillán EO, Morales-Martínez M, Madrigal-Bujaidar E, et al. Oxidative stress, mitochondrial function and adaptation to exercise: new perspectives in nutrition. Life (Basel) 2021; 11(11): 1269. doi: 10.3390/life11111269


41.
Kim MB, Kim T, Kim C, Hwang JK. Standardized Kaempferia parviflora extract enhances exercise performance through activation of mitochondrial biogenesis. J Med Food 2018; 21(1): 30–8. doi: 10.1089/jmf.2017.3989


42.
Mao GX, Xu XG, Wang SY, Li HF, Zhang J, Zhang ZS, et al. Salidroside delays cellular senescence by stimulating mitochondrial biogenesis partly through a miR-22/SIRT-1 pathway. Oxid Med Cell Longev 2019; 2019: 5276096. doi: 10.1155/2019/5276096


43.
Akbari-Fakhrabadi M, Najafi M, Mortazavian S, Rasouli M, Memari AH, Shidfar F. Effect of saffron (Crocus sativus L.) and endurance training on mitochondrial biogenesis, endurance capacity, inflammation, antioxidant, and metabolic biomarkers in Wistar rats. J Food Biochem 2019; 43(8): e12946. doi: 10.1111/jfbc.12946


44.
Vincent AE, Rosa HS, Pabis K, Lawless C, Chen C, Grünewald A, et al. Subcellular origin of mitochondrial DNA deletions in human skeletal muscle. Ann Neurol 2018; 84(2): 289–301. doi: 10.1002/ana.25288


45.
Reid SNS, Park JH, Kim Y, Kwak YS, Jeon BH. In vitro and in vivo effects of fermented oyster-derived lactate on exercise endurance indicators in mice. Int J Environ Res Public Health 2020; 17(23): 8811. doi: 10.3390/ijerph17238811


46.
Accattato F, Greco M, Pullano SA, Carè I, Fiorillo AS, Pujia A, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PLoS One 2017; 12: e0178900. doi: 10.1371/journal.pone.0178900


47.
Petterson J, Hindorf U, Persson P, Bengtsson T, Malmqvist U, Werkström V, et al. Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol 2008; 65(2): 253–9. doi: 10.1111/j.1365-2125.2007.03001.x


48.
Spada TC, Silva JMRD, Francisco LS, Marçal LJ, Antonangelo L, Zanetta DMT, et al. High intensity resistance training causes muscle damage and increases biomarkers of acute kidney injury in healthy individuals. PLoS One 2018; 13(11): e0205791. doi: 10.1371/journal.pone.0205791
Published
2023-10-30
How to Cite
Sinha S., Alluri K. V., Somepalli V., Golakoti T., & Sengupta K. (2023). A synergistic blend of <em>Garcinia mangostana</em> fruit rind and <em>Cinnamomum tamala</em&gt; leaf extracts enhances myogenic differentiation and mitochondrial biogenesis in vitro and muscle growth and strength in mice. Food & Nutrition Research, 67. https://doi.org/10.29219/fnr.v67.9750
Section
Original Articles