Abstract
Objective
To investigate the effect of hydrogen-rich Korean Red Ginseng (KRG) water (HRGW) mixture on the spermatogenesis and sperm motility of mice of different ages.
Methods
Eighty young (3 month-old) and aged (12 month-old) male mice were randomly assigned to 4 groups (n =10 per group) including control group, hydrogen-rich water (HRW) group (10 mL/kg daily), KRG group (50 mg/kg daily) and HRGW group (10 mL/kg and 50 mg/kg daily) by an oral zoned needle for 4 weeks. Sperm count and motility were measured using sperm suspension released from cauda epididymis. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and reactive oxygen species (ROS) in serum have also been estimated. Tubular changes were examined through histological hematoxylin and eosin staining. Expression of antioxidation (PPx3, PPx4, GSTm5 and GPx4), spermatogenesis (inhibin-a, neptin-2 and CREM), antiaging (SIRT1 and SIRT2), and angiogenesis [visfatin and vascular endothelial growth factor (VEGF)] related genes were examined through real-time polymerase chain reaction.
Results
HRW and KRG treatment stimulated spermatogenesis followed by increasing sperm production and sperm motility (P <0.05). These effects were strengthened synergistically by a HRGW mixture (P <0.05 or P <0.01). HRGW greatly increased the expressions of antioxidation, antiaging, spermatogenesis related genes and VEGF especially in aged mice (P <0.05). Serum testosterone and FSH levels also increased, while serum ROS level decreased (all P <0.05).
Conclusion
HRGW increases sperm production and motility by enhancing antioxidation and stimulating spermatogenesis and sex hormone production, particularly in aged mice.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med 2012;9:e1001356.
Smith JF, Eisenberg ML, Millstein SG, Nachtigall RD, Shindel AW, Wing H, et al. The use of complementary and alternative fertility treatment in couples seeking fertility care: data from a prospective cohort in the United States. Fertil Steril 2010;93:2169–2174.
Harris ID, Fronczak C, Roth L, Meacham RB. Fertility and the aging male. Rev Urol 2011;13:184–190.
Winters BR, Walsh TJ. The epidemiology of male infertility. Urol Clin North Am 2014;41:195–204.
Nudell DM, Monoski MM, Lipshultz LI. Common medications and drugs: how they affect male fertility. Urol Clin North Am 2002;29:965–973.
Stankiewicz M, Smith C, Alvino H, Norman R. The use of complementary medicine and therapies by patients attending a reproductive medicine unit in South Australia: a prospective survey. Aust N Z J Obstet Gynaecol 2007;47:145–149.
Bardaweel SK, Shehadeh M, Suaifan GA, Kilani MV. Complementary and alternative medicine utilization by a sample of infertile couples in Jordan for infertility treatment: clinics-based survey. BMC Complement Altern Med 2013;13:1–7.
Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod 1989;41:183–197.
Aitken RJ, Clarkson JS. Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 1987;81:459–469.
Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril 1992;57:409–416.
Cummins JM, Jequier AM, Kan R. Molecular biology of human male infertility: links with aging, mitochondrial genetics, and oxidative stress? Mol Reprod Dev 1994;37:345–362.
Rajesh Kumar T, Muralidhara. Oxidative stress response of rat testis to model prooxidants in vitro and its modulation. Toxicol In Vitro 2002;16:675–682.
Rajeswary S, Kumaran B, Ilangovan R, Yuvaraj S, Sridhar M, Venkataraman P, et al. Modulation of antioxidant defense system by the environmental fungicide carbendazim in Leydig cells of rats. Reprod Toxicol 2007;24:371–380.
Kiefer D, Pantuso T. Panax ginseng. Am Fam Phys 2003;68:1539–1542.
Ramesh T, Kim SW, Hwang SY, Sohn SH, Yoo SK, Kim SK. Panax ginseng reduces oxidative stress and restores antioxidant capacity in aged rats. Nutr Res 2012;32:718–726.
Leung KW, Wong AS. Ginseng and male reproductive function. Spermatogenesis 2013;3:e26391.
Won YJ, Kim BK, Shin YK, Jung SH, Yoo SK, Hwang SY, et al. Pectinase-treated Panax ginseng extract (GINST) rescues testicular dysfunction in aged rats via redoxmodulating proteins. Exp Gerontol 2014;53:57–66.
Oliynyk S, Oh S. Actoprotective effect of ginseng: improving mental and physical performance. J Ginseng Res 2013;37:144–166.
Yun TK. Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16 Suppl:S3–S5.
Kim YH, Kim GH, Shin JH, Kim KS, Lim JS. Effect of Korean red ginseng on testicular tissue injury after torsion and detorsion. Korean J Urol 2010;51:794–799.
Zheng GQ, Cheng W, Wang Y, Wang XM, Zhao SZ, Zhou Y, et al. Ginseng total saponins enhance neurogenesis after focal cerebral ischemia. J Ethnopharmacol 2011;133:724–728.
Yayeh T, Jung KH, Jeong HY, Park JH, Song YB, Kwak YS, et al. Korean red ginseng saponin fraction downregulates proinflammatory mediators in LPS stimulated RAW264.7 cells and protects mice against endotoxic shock. J Ginseng Res 2012;36:263–269.
Hwang SY, Kim WJ, Wee JJ, Choi JS, Kim SK. Panax ginseng improves survival and sperm quality in guinea pigs exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. BJU Intern 2004;94:663–668.
Park HJ, Choe S, Park NC. Effects of Korean red ginseng on semen parameters in male infertility patients: a randomized, placebo-controlled, double-blind clinical study. Chin J Integr Med 2016;22:490–495.
Kopalli SR, Hwang SY, Won YJ, Kim SW, Cha KM, Han CK, et al. Korean red ginseng extract rejuvenates testicular ineffectiveness and sperm maturation process in aged rats by regulating redox proteins and oxidative defense mechanisms. Exp Gerontol 2015;69:94–102.
Dixon BJ, Tang J, Zhang JH. The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance. Med Gas Res 2013;3:10.
Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007;13:688–694.
Huang CS, Kawamura T, Toyoda Y, Nakao A. Recent advances in hydrogen research as a therapeutic medical gas. Free Radic Res 2010;44:971–982.
Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 2008;28:137–143.
Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome—an open label pilot study. J Clin Biochem Nutr 2010;46:140–149.
Ohno K, Ito M, Ichihara M, Ito M. Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxid Med Cell Longev 2012;2012:353152.
Li Q, Kato S, Matsuoka D, Tanaka H, Miwa N. Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro. Med Gas Res 2013;3:20.
Nakata K, Yamashita N, Noda Y, Ohsawa I. Stimulation of human damaged sperm motility with hydrogen molecule. Med Gas Res 2015;5:2.
Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol 2009;64:753–761.
Hou Y, Zhang Y, Li G, Xiang W, Li H. Microsurgical epididymal cystectomy does not impact upon sperm count, motility or morphology and is a safe and effective treatment for epididymal cystic lesions (ECLs) in young men with fertility requirements. Urology 2018;pii:S0090–4295(18) 30831–30838.
Park HJ, Koo YK, Park MJ, Hwang YK, Hwang SY, Park NC. Restoration of spermatogenesis using a new combined herbal formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an luteinizing hormone-releasing hormone agonist-induced rat dodel of male infertility. World J Mens Health 2017;35:170–177.
Park WS, Shin DY, Kim DR, Yang WM, Chang MS, Park SK. Korean ginseng induces spermatogenesis in rats through the activation of cAMP-responsive element modulator (CREM). Fertil Steril 2007;88:1000–1002.
Yang WM, Park SY, Kim HM, Park EH, Park SK, Chang MS. Effects of Panax ginseng on glial cellderived neurotrophic factor (GDNF) expression and spermatogenesis in rats. Phytother Res 2011;25:308–311.
Cao L, Leers-Sucheta S, Azhar S. Aging alters the functional expression of enzymatic and non-enzymatic antioxidant defense systems in testicular rat Leydig cells. J Steroid Biochem Mol Biol 2004;88:61–67.
LeCouter J, Ferrara N. EG-VEGF and the concept of tissuespecific angiogenic growth factors. Semin Cell Dev Biol 2002;13:3–8.
Kilinc F, Kayaselcuk F, Aygun C, Guvel S, Egilmez T, Ozkardes H. Experimental varicocele induces hypoxia inducible factor-1alpha, vascular endothelial growth factor expression and angiogenesis in the rat testis. J Urol 2004;172:1188–1191.
Tek M, Cayan S, Yilmaz N, Oguz I, Erdem E, Akbay E. The effect of vascular endothelial growth factor on spermatogenesis and apoptosis in experimentally varicoceleinduced adolescent rats. Fertil Steril 2009;91:2247–2252.
Gokhan-Kose M, Erdem SR, Peskircioglu CL, Caylak B. Angiogenesis inhibition impairs testicular morphology in experimental left varicocele rat model. Actas Urologicas Espanolas 2014;38:459–464.
Hong Y, Chen S, Zhang JM. Hydrogen as a selective antioxidant: a review of clinical and experimental studies. J Int Med Res 2010;38:1893–1903.
Author information
Authors and Affiliations
Contributions
Ku JY contributed to execution of study, acquisition of data, and manuscript drafting. Park MJ performed the study and statistical analysis; Park HJ and Park NC performed the data analysis and critical discussion. Joo BS contributed to conception and design of study, drafting the manuscript and revising it critically for important intellectual content, and approval for final version for publication.
Corresponding author
Ethics declarations
All authors have no conflicts of interest to declare.
Rights and permissions
About this article
Cite this article
Ku, J.Y., Park, M.J., Park, H.J. et al. Combination of Korean Red Ginseng Extract and Hydrogen-Rich Water Improves Spermatogenesis and Sperm Motility in Male Mice. Chin. J. Integr. Med. 26, 361–369 (2020). https://doi.org/10.1007/s11655-019-3047-1
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-019-3047-1