A 14-week randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy and safety of ginseng polysaccharide (Y-75)

Young-Jin Cho, Hyeog-Jin Son, Kyung-Soo Kim, Young-Jin Cho, Hyeog-Jin Son, Kyung-Soo Kim

Abstract

Background: The Y-75 (Ginsan) acidic polysaccharide from Korean Panax ginseng has been shown to function as an immunomodulatory molecule. However, the efficacy of Y-75 has not been evaluated in clinical trial.

Methods: We verified Y-75 (6 g/day) for safety and immune efficacy in 72 healthy volunteers aged 50-75 years using a randomized, placebo-controlled, parallel, double-blind study. The activities of natural killer (NK) cells and peripheral blood phagocytes, as well as serum levels of monocyte-derived mediators, were assessed before and after administration for 8 and 14 weeks. This trial is registered at ClinicalTrials.gov (NCT02161198).

Results: Y-75 significantly enhanced NK cell cytotoxic activity by 35.2% and 40.2% from baseline after administration for 8 and 14 weeks, respectively. The phagocytic activity of peripheral blood cells was also significantly increased by 25.2% and 39.4% and serum level of TNF-α by 38.2% and 44.5% after treatment for 8 and 14 weeks, respectively. Differences in the efficacy of variables compared to the placebo group were also significant. Administration of Y-75 was well tolerated without treatment-related adverse events or alteration of complete blood cell count or blood chemistry over the entire study period.

Conclusion: Y-75 was shown to be a safe and potentially effective natural alternative for enhancing immune function.

Figures

Figure 1
Figure 1
Flow-chart of the study.
Figure 2
Figure 2
Changes in cytotoxic activity of NK cells (A), activity of phagocytes (B), and monocyte-derived mediator (TNF-α and IL-12) levels (C, D) during the study period. Data are mean ± SE. ** P <0.01 different from baseline, †P <0.05, †† P <0.01 different from the placebo group.

References

    1. Radad K, Gille G, Liu L, Rausch WD. Use of ginseng in medicine with emphasis on neurodegenerative disorders. J Pharmacol Sci. 2006;100:175–186. doi: 10.1254/jphs.CRJ05010X.
    1. Jia L, Zhao Y. Current evaluation of the millennium phytomedicine–ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations. Curr Med Chem. 2009;16(19):2475–2484. doi: 10.2174/092986709788682146.
    1. Kang S, Min H. Ginseng, the ‘Immunity Boost’: the effects of Panax ginseng on immune system. J Ginseng Res. 2012;36(4):354–368. doi: 10.5142/jgr.2012.36.4.354.
    1. Kim DH. Chemical Diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res. 2012;36(1):1–15. doi: 10.5142/jgr.2012.36.1.1.
    1. Yin SY, Kim HJ, Kim HJ. A comparative study of the effects of whole red ginseng extract and polysaccharide and saponin fractions on influenza A (H1N1) virus infection. Biol Pharm Bull. 2013;36(6):1002–1007. doi: 10.1248/bpb.b13-00123.
    1. Yoo DG, Kim MC, Park MK, Park KM, Quan FS, Song JM, Wee JJ, Wang BZ, Cho YK, Compans RW, Kang SM. Protective effect of ginseng polysaccharides on influenza viral infection. PLoS One. 2012;7(3):e33678. doi: 10.1371/journal.pone.0033678.
    1. Wang Z, Meng J, Xia Y, Meng Y, Du L, Zhang Z, Wang E, Shan F. Maturation of murine bone marrow dendritic cells induced by acidic Ginseng polysaccharides. Int J Biol Macromol. 2013;53:93–100. doi: 10.1016/j.ijbiomac.2012.11.009.
    1. Byeon SE, Lee J, Kim JH, Yang WS, Kwak YS, Kim SY, Choung ES, Rhee MH, Cho JY. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean red ginseng. Mediators Inflamm. 2012;2012:732860.
    1. Lim TS, Na K, Choi EM, Chung JY, Hwang JK. Immunomodulating activities of polysaccharides isolated from Panax ginseng. J Med Food. 2004;7(1):1–6. doi: 10.1089/109662004322984626.
    1. Shin HJ, Kim YS, Kwak YS, Song YB, Kim YS, Park JD. Enhancement of antitumor effects of paclitaxel (taxol) in combination with red ginseng acidic polysaccharide (RGAP) Planta Med. 2004;70(11):1033–1038. doi: 10.1055/s-2004-832643.
    1. Gao H, Wang F, Lien EJ, Trousdale MD. Immunostimulating polysaccharides from Panax notoginseng. Pharm Res. 1996;13(8):1196–1200. doi: 10.1023/A:1016060119425.
    1. Du XF, Jiang CZ, Wu CF, Won EK, Choung SY. Synergistic immunostimulating activity of pidotimod and red ginseng acidic polysaccharide against cyclophosphamide-induced immunosuppression. Arch Pharm Res. 2008;31(9):1153–1159. doi: 10.1007/s12272-001-1282-6.
    1. Yun YS, Lee YS, Jo SK, Jung IS. Inhibition of autochthonous tumor by ethanol insoluble fraction from Panax ginseng as an immunomodulator. Planta Med. 1993;59(6):521–524. doi: 10.1055/s-2006-959752.
    1. Lee YS, Chung IS, Lee IR, Kim KH, Hong WS, Yun YS. Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng. Anticancer Res. 1997;17(1a):323–331.
    1. Ko EJ, Joo HG. Stimulatory effects of ginsan on the proliferation and viability of mouse spleen cells. Korean J Physiol Pharmacol Off J Korean Physiol Soc Korean Soc Pharmacol. 2010;14(3):133–137. doi: 10.4196/kjpp.2010.14.3.133.
    1. Kim MH, Byon YY, Ko EJ, Song JY, Yun YS, Shin T, Joo HG. Immunomodulatory activity of ginsan, a polysaccharide of panax ginseng, on dendritic cells. Korean J Physiol Pharmacol. 2009;13(3):169–173. doi: 10.4196/kjpp.2009.13.3.169.
    1. Kim HJ, Kim MH, Byon YY, Park JW, Jee Y, Joo HG. Radioprotective effects of an acidic polysaccharide of Panax ginseng on bone marrow cells. J Vet Sci. 2007;8(1):39–44. doi: 10.4142/jvs.2007.8.1.39.
    1. Shin JY, Song JY, Yun YS, Yang HO, Rhee DK, Pyo S. Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function. Immunopharmacol Immunotoxicol. 2002;24(3):469–482. doi: 10.1081/IPH-120014730.
    1. Song JY, Han SK, Son EH, Pyo SN, Yun YS, Yi SY. Induction of secretory and tumoricidal activities in peritoneal macrophages by ginsan. Int Immunopharmacol. 2002;2(7):857–865. doi: 10.1016/S1567-5769(01)00211-9.
    1. Han SK, Song JY, Yun YS, Yi SY. Ginsan improved Th1 immune response inhibited by gamma radiation. Arch Pharm Res. 2005;28(3):343–350. doi: 10.1007/BF02977803.
    1. Hwang I, Ahn G, Park E, Ha D, Song JY, Jee Y. An acidic polysaccharide of Panax ginseng ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells. Immunol Lett. 2011;138(2):169–178. doi: 10.1016/j.imlet.2011.04.005.
    1. Kim KH, Lee YS, Jung IS, Park SY, Chung HY, Lee IR, Yun YS. Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2. Planta Med. 1998;64(2):110–115. doi: 10.1055/s-2006-957385.
    1. Shim JY, Han Y, Ahn JY, Yun YS, Song JY. Chemoprotective and adjuvant effects of immunomodulator ginsan in cyclophosphamide-treated normal and tumor bearing mice. Int J Immunopathol Pharmacol. 2007;20(3):487–497.
    1. Song JY, Han SK, Bae KG, Lim DS, Son SJ, Jung IS, Yi SY, Yun YS. Radioprotective effects of ginsan, an immunomodulator. Radiat Res. 2003;159(6):768–774. doi: 10.1667/0033-7587(2003)159[0768:REOGAI];2.
    1. Na HS, Lim YJ, Yun YS, Kweon MN, Lee HC. Ginsan enhances humoral antibody response to orally delivered antigen. Immune network. 2010;10(1):5–14. doi: 10.4110/in.2010.10.1.5.
    1. Ahn JY, Song JY, Yun YS, Jeong G, Choi IS. Protection of Staphylococcus aureus-infected septic mice by suppression of early acute inflammation and enhanced antimicrobial activity by ginsan. FEMS Immunol Med Microbiol. 2006;46(2):187–197. doi: 10.1111/j.1574-695X.2005.00021.x.
    1. Ahn JY, Choi IS, Shim JY, Yun EK, Yun YS, Jeong G, Song JY. The immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Toll-like receptor-mediated inflammatory signals. Eur J Immunol. 2006;36(1):37–45. doi: 10.1002/eji.200535138.
    1. Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep. 2011;28(3):467–495. doi: 10.1039/c0np00057d.
    1. Tomoda M, Hirabayashi K, Shimizu N, Gonda R, Ohara N. The core structure of ginsenan PA, a phagocytosis-activating polysaccharide from the root of Panax ginseng. Biol Pharm Bull. 1994;17(9):1287–1291. doi: 10.1248/bpb.17.1287.
    1. Tomoda M, Hirabayashi K, Shimizu N, Gonda R, Ohara N, Takada K. Characterization of two novel polysaccharides having immunological activities from the root of Panax ginseng. Biol Pharm Bull. 1993;16(11):1087–1090. doi: 10.1248/bpb.16.1087.
    1. Tomoda M, Takeda K, Shimizu N, Gonda R, Ohara N, Takada K, Hirabayashi K. Characterization of two acidic polysaccharides having immunological activities from the root of Panax ginseng. Biol Pharm Bull. 1993;16(1):22–25. doi: 10.1248/bpb.16.22.
    1. Yang JC, Pang CS, Tsang SF, Ng KF. Effect of American ginseng extract (Panax quinquefolius) on formalin-induced nociception in mice. Am J Chin Med. 2001;29(1):149–154. doi: 10.1142/S0192415X01000162.
    1. High KP, Case D, Hurd D, Powell B, Lesser G, Falsey AR, Siegel R, Metzner-Sadurski J, Krauss JC, Chinnasami B, Sanders G, Rousey S, Shaw EG. A randomized, controlled trial of Panax quinquefolius extract (CVT-E002) to reduce respiratory infection in patients with chronic lymphocytic leukemia. J Support Oncol. 2012;10(5):195–201. doi: 10.1016/j.suponc.2011.10.005.
    1. McElhaney JE, Goel V, Toane B, Hooten J, Shan JJ. Efficacy of COLD-fX in the prevention of respiratory symptoms in community-dwelling adults: a randomized, double-blinded, placebo controlled trial. J Altern Complement Med. 2006;12(2):153–157. doi: 10.1089/acm.2006.12.153.
    1. McElhaney JE, Gravenstein S, Cole SK, Davidson E, O’neill D, Petitjean S, Rumble B, Shan JJ. A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults. J Am Geriatr Soc. 2004;52(1):13–19. doi: 10.1111/j.1532-5415.2004.52004.x.
    1. McElhaney JE, Simor AE, McNeil S, Predy GN. Efficacy and Safety of CVT-E002, a proprietary extract of Panax quinquefolius in the prevention of respiratory infections in influenza-vaccinated community-dwelling adults: a multicenter, randomized, double-blind, and placebo-controlled trial. Influenza Res Treat. 2011;2011:759051.
    1. Shergis JL, Zhang AL, Zhou W, Xue CC. Panax ginseng in randomised controlled trials: a systematic review. Phytother Res. 2013;27(7):949–965. doi: 10.1002/ptr.4832.
    1. Siegel RK. Ginseng abuse syndrome. Problems with the panacea. JAMA. 1979;241(15):1614–1615. doi: 10.1001/jama.1979.03290410046024.
    1. Choi J, Kim TH, Choi TY, Lee MS. Ginseng for health care: a systematic review of randomized controlled trials in Korean literature. PLoS One. 2013;8(4):e59978. doi: 10.1371/journal.pone.0059978.
    1. Eiwegger T, Stahl B, Haidl P, Schmitt J, Boehm G, Dehlink E, Urbanek R, Szepfalusi Z. Prebiotic oligosaccharides: in vitro evidence for gastrointestinal epithelial transfer and immunomodulatory properties. Pediatr Allergy Immunol. 2010;21(8):1179–1188. doi: 10.1111/j.1399-3038.2010.01062.x.
    1. Jeurink PV, van Esch BC, Rijnierse A, Garssen J, Knippels LM. Mechanisms underlying immune effects of dietary oligosaccharides. Am J Clin Nutr. 2013;98(2):572s–577s. doi: 10.3945/ajcn.112.038596.
    1. Wee JJ, Mee Park K, Chung AS. Biological Activities of Ginseng and Its Application to Human Health. In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. Boca Raton (FL): CRC Press Llc; 2011.

Source: PubMed

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