DOI QR코드

DOI QR Code

Immunomodulatory and anti-metastatic activities of a crude polysaccharide isolated from Korean apple vinegar

한국산 사과식초에서 분리한 다당의 면역 및 항전이 활성

  • Kim, Han Wool (Department of Food Science and Biotechnology, Kyonggi University) ;
  • Shin, Kwang-Soon (Department of Food Science and Biotechnology, Kyonggi University)
  • 김한울 (경기대학교 식품생물공학과) ;
  • 신광순 (경기대학교 식품생물공학과)
  • Received : 2019.01.14
  • Accepted : 2019.01.31
  • Published : 2019.04.30

Abstract

To characterize new physiologically active components in Korean apple vinegar, a crude polysaccharide (KAV-0) was prepared by precipitation with 80% (v/v) ethanol. KAV-0 mainly comprises 38.2% mannose, 19.1% galactose and 14.3% glucose. In an in vitro cytotoxicity analysis, KAV-0 promoted the proliferation of peritoneal macrophages and RAW 264.7 cells in a dose-dependent manner, and showed no cytotoxicity in B16-BL6 melanoma cells. Murine peritoneal macrophages and RAW 264.7 cells stimulated by KAV-0 produced various cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$, and nitric oxide (NO). Intravenous (i.v.) administration of KAV-0 significantly augmented NK cell cytotoxicity against Yac-1 tumor cells. In experimental lung metastasis caused by B16-BL6 melanomas, prophylactic i.v. administration of KAV-0 at a dosage of $1,000{\mu}g/mouse$ inhibited lung metastasis by 53.0%. These results suggest that the crude polysaccharide (KAV-0) isolated from Korean apple vinegar has a considerably high anti-metastatic activity and immunomodulatory activities beneficial to human health.

SPGHB5_2019_v51n2_152_f0001.png 이미지

Fig. 1. Isolation of (immuno-stimulating) polysaccharide (KAV- 0) isolated from Korean apple vinegars (A), and elution pattern and MW-determination of KAV-0 on HPSEC (B).

SPGHB5_2019_v51n2_152_f0002.png 이미지

Fig. 2. Effect of KAV-0 on viabilities of murine peritoneal macrophages, RAW 264.7 and B16-BL6 melanoma cells.

SPGHB5_2019_v51n2_152_f0003.png 이미지

Fig. 3. Effect of KAV-0 on cytokines and nitric oxide production by RAW 264.7 cells. RAW 264.7 cells were treated with indicated concentrations of KAV-0 for 24 hr.

SPGHB5_2019_v51n2_152_f0004.png 이미지

Fig. 4. Effect of KAV-0 on cytokines and nitric oxide production by murine peritoneal macrophage in vitro.

SPGHB5_2019_v51n2_152_f0005.png 이미지

Fig. 5. Effect of KAV-0 on cytolytic activity of NK cells ex vivo.

SPGHB5_2019_v51n2_152_f0006.png 이미지

Fig. 6. Inhibitory effect of KAV-0 on lung metastasis produced by i.v. inoculation of B16-BL6 melanoma cells.

Table. 1. Chemical properties of KAV-0 isolated from apple vinegar

SPGHB5_2019_v51n2_152_t0001.png 이미지

Acknowledgement

Supported by : 경기대학교

References

  1. Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17: 593-623 (1999) https://doi.org/10.1146/annurev.immunol.17.1.593
  2. Ballou CE. A study of the immunochemistry of three yeast mannans. J. Biol. Chem. 245: 1197-1203 (1970)
  3. Bao X, Wang Z, Fang J, Li X. Structural Features of an immunostimulating and antioxidant acidic polysaccharide from the seeds of cuscuta chinensis. Planta Med. 68: 237-243 (2002) https://doi.org/10.1055/s-2002-23133
  4. Belardelli F. Role of interferons and other cytokines in the regulation of the immune response. Apmis 103: 161-179 (1995) https://doi.org/10.1111/j.1699-0463.1995.tb01092.x
  5. Blumenkrantz N, Asboe-Hansen G. New method for quantitative determination of uronic acids. Anal. Biochem. 54: 484-489 (1973) https://doi.org/10.1016/0003-2697(73)90377-1
  6. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal. Biochem. 72: 248-254 (1976) https://doi.org/10.1016/0003-2697(76)90527-3
  7. Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Gately MK. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J. Exp. Med. 178: 1223-1230 (1993) https://doi.org/10.1084/jem.178.4.1223
  8. Byun EH. Immunomodulatory activities of crude polysaccharide fraction separated from Perilla frutescens Britton var. acuta Kudo. Korean J. Food Sci. Technol. 49: 559-566 (2017)
  9. Dubois M, Gilles KA, Hamilton JK, Rebers PT, Smith F. Colorimetric method for determination of sugars and related substances. Anal. Chem. 28: 350-356 (1956) https://doi.org/10.1021/ac60111a017
  10. Farag SS, Fehniger TA, Ruggeri L, Velardi A, Caligiuri MA. Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood 100: 1935-1947 (2002) https://doi.org/10.1182/blood-2002-02-0350
  11. Funk J, Schmitz G, Bach U. Influence of different tumour types on natural cytotoxicity (NK cell activity) and mitogen-induced lymphocyte proliferation in isolated blood lymphocytes from 110 dogs with tumours. Res. Vet. Sci. 74: 129-135. (2003) https://doi.org/10.1016/S0034-5288(02)00157-1
  12. Hong HD. New technology-immunoregulatory actions of polysaccharides from natural plant resources. Bull. Food Technol. 24: 390-409 (2011)
  13. Hong SM, Kang MJ, Lee JH, Jeong JH, Kwon SH, Seo KI. Production of Vinegar using Rubus coreanus and Its Antioxidant Activities. Korean J. Food Preserv. 19: 594-603 (2012) https://doi.org/10.11002/kjfp.2012.19.4.594
  14. Jeong YJ. Current trends and future prospects in the Korean vinegar industry. Food Sci. Ind. 42: 52-59 (2009)
  15. Jones TM, Albersheim P. A gas chromatographic method for the determination of aldose and uronic acid constituents of plant cell wall polysaccharides. Plant Physiol. 49: 926-936 (1972) https://doi.org/10.1104/pp.49.6.926
  16. Kagi D, Ledermann B, Burki K, Seiler P, Odermatt B, Olsen KJ, Podack ER, Zinkernagel RM, Hengartner H. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 368: 31-37 (1994)
  17. Karkhanis YD, Zeltner JY, Jackson JJ, Carlo DJ. A new and improved microassay to determine 2-keto-3-deoxyoctonate in lipopolysaccharide of Gram-negative bacteria. Anal. Biochem. 85: 595-601 (1978) https://doi.org/10.1016/0003-2697(78)90260-9
  18. Kim DS, Hurh BS, Shin KS. Chemical characteristics and immunostimulatory activity of polysaccharides from fermented vinegars manufactured with different raw materials. J. Korean Soc. Food Sci. Nutr. 44: 191-199 (2015) https://doi.org/10.3746/jkfn.2015.44.2.191
  19. Kim DS, Shin KS. chemical property and macrophage stimulating activity of polysaccharides isolated from brown rice and persimmon vinegars. Korean J. Food Nutr. 27: 1033-1042 (2014) https://doi.org/10.9799/ksfan.2014.27.6.1033
  20. Ko HS, Park MN, Kim BL, Yoon TJ, Song HS, Cho SY, Kim SH. Anti-metastatic activity of water extract of samguikoeuitang via enhancement of natural killer cells. J. Korean Traditional Oncol. 15: 29-36 (2010)
  21. Kroncke KD, Fehsel K, Kolb-Bachofen V. Inducible nitric oxide synthase in human diseases. Clin. Exp. Immunol. 113: 147-156 (1998) https://doi.org/10.1046/j.1365-2249.1998.00648.x
  22. Kuby J, Osborne BA, Kindt TJ, Goldsby RA. Immunology. 5th ed. W.H. Freeman and company. Richmond, TX, USA pp. 9-75 (2006)
  23. Kwak BS, Park HR, Lee SJ, Choi HJ, Shin KS. chemical properties and assessment of immunomodulatory activities of extracts isolated from broccoli. Korean J. Food Nutr. 30: 1140-1148 (2017)
  24. Kwon SH, Jeong EJ, Lee GD, Jeong YJ. Preparation method of fruit vinegars by two stage fermentation and beverages including vinegar. Food Ind. Nutr. 5: 18-24 (2000)
  25. Le Bourvellec C, Bouchet B, Renard CMGC. Non-covalent interaction between procyanidins and apple cell wall material. Part III: Study on model polysaccharides. Biochim. Biophys. Acta 1725: 10-18 (2005) https://doi.org/10.1016/j.bbagen.2005.06.004
  26. Lee YC, Lee JH. A manufacturing process of high-strength vinegars. Food Ind. Nutr. 5: 13-17 (2000)
  27. Lee EH, Park HR, Shin MS, Cho SY, Choi HJ, Shin KS. Antitumor metastasis activity of pectic polysaccharide purified from the peels of Korean citrus Hallabong. Carbohydr. Polym. 111: 72-79 (2014) https://doi.org/10.1016/j.carbpol.2014.04.073
  28. MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu. Rev. Immunol. 15: 323-350 (1997) https://doi.org/10.1146/annurev.immunol.15.1.323
  29. Meyers RA. Immunology: from Cell Biology to Disease. 1st ed. Wiley-VCH. Weinheim, Germany pp.102-107. (2007)
  30. Park HR, Hwang D, Hong HD, Shin KS. Antitumor and antimetastatic activities of pectic polysaccharides isolated from persimmon leaves mediated by enhanced natural killer cell activity. J. Funct. Foods 37: 460-466 (2017) https://doi.org/10.1016/j.jff.2017.08.027
  31. Sakanaka S, Ishihara Y. Comparison of antioxidant properties of persimmon vinegar and some other commercial vinegars in radicalscavenging assays and on lipid oxidation in tuna homogenates. Food Chem. 107: 739-744 (2008) https://doi.org/10.1016/j.foodchem.2007.08.080
  32. Seok H, Lee JY, Park EM, Park SE, Lee JH, Lim S, Cha BS. Balsamic vinegar improves high fat-induced beta cell dysfunction via beta cell ABCA1. Diabetes metab. J. 36: 275-279 (2012) https://doi.org/10.4093/dmj.2012.36.4.275
  33. Shin KS, Kiyohara H, Matsumoto T, Yamada H. Rhamnogalacturonan II from the leaves of Panax ginseng C.A. Meyer as a macrophage Fc receptor expression-enhancing polysaccharide. Carbohydr. Res. 300: 239-249 (1997) https://doi.org/10.1016/S0008-6215(97)00055-4
  34. Shin YA, Park HR, Hong HD, Shin KS. Immuno-stimulating Activities of Polysaccharide Fractions Isolated from Persimmon Leaves. Korean J. Food Nutr. 25: 941-950 (2012) https://doi.org/10.9799/ksfan.2012.25.4.941
  35. Singleton V, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am. J. Enol. Vitic. 16: 144-158 (1965)
  36. Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, Takeda K, Van Dommelen SLH, Degil-Esposti MA, Hayakawa Y. Activation of NK cell cytotoxicity. Mol. Immunol. 42: 501-510 (2005) https://doi.org/10.1016/j.molimm.2004.07.034
  37. Vogel RA, Corretti MC, Plotnick GD. The postprandial effect of components of the Mediterranean diet on endothelial function. J. Am. Coll. Cardiol. 36: 1455-1460 (2000) https://doi.org/10.1016/S0735-1097(00)00896-2
  38. Zhu H, Zhang Y, Zhang J, Chen D. Isolation and characterization of an anti-complementary protein-bound polysaccharide from the stem barks of Eucommia ulmoides. Int. Immunopharmacol. 8: 1222-1230 (2008) https://doi.org/10.1016/j.intimp.2008.04.012