Isolation and Characterization of Intestinal Immune System Modulating and Anticancer Active Fractions from the Herbal Prescriptions

  • Hwang, Jong-Hyun (Division of Food and Biotechnology, Chungju National University) ;
  • Jeong, Jae-Hyun (Division of Food and Biotechnology, Chungju National University) ;
  • Yu, Kwang-Won (Division of Food and Biotechnology, Chungju National University)
  • Published : 2009.04.30

Abstract

The prescriptions (DB-1-DB-5) were prepared with the active herbal medicines, Acanthopanax senticosus, Glycyrrhiza uralensis, Polygonatum odoratum, and Cichorium intybus. The most active crude polysaccharide fraction (DB-2-3), which was isolated through the fractionation of hot-water extract from DB-2, was significantly reduced by periodate oxidation (52.7 and 63.7%) on intestinal immune system modulating and anticancer activity. When DB-2-3 was further fractionated by column chromatographies, DB-2-3IIc-2 showed the most potent activities. In addition, DB-2-3IIc stimulated the proliferation of bone marrow cells via Peyer's patch in dose-dependent pattern by oral administration. The metastasis of colon 26-M3.1 lung carcinoma had significantly inhibited in mice fed DB-2-3IIc at 1 mg/mouse (43.8%). DB-2-3IIc-2 mainly contained uronic acid (46.1%) and 42.5% of neutral sugar with a small amount of protein (7.6%), and component sugar analysis also showed that DB-2-3IIc-2 was composed Ara, Gal, and GalA (molar ratio; 0.50:0.63:1.00). It may be suggested that activities of DB-2-3IIc-2 are resulted from pectic polysaccharides containing a polygalacturonan moiety with side chain of neutral sugars, such as Ara and Gal.

Keywords

References

  1. Ishih A, Miyase T, Terada M. Comparison of antimalarial activity of the alkaloidal fraction of Hydrangea macrophylla var. Otaksa leaves with the hot-water extraction in ICR mice infected with Plasmodium yoelii 17XL. Phytother. Res. 17: 633-639 (2003) https://doi.org/10.1002/ptr.1215
  2. Yu KW, Kiyohara H, Matsumoto T, Yang HC, Yamada H. Structural characterization of intestinal immune system modulating new arabino-3,6-galactan from rhizomes of Atractylodes lancea DC. Carbohyd. Polym. 46: 147-156 (2001) https://doi.org/10.1016/S0144-8617(00)00294-0
  3. Wiboonsirikul J, Kimura Y, Kanaya Y, Tsuno T, Adachi S. Production and characterization of functional substances from a byproduct of rice bran oil and protein production by a compressed hot water treatment. Biosci. Biotech. Bioch. 72: 384-392 (2008) https://doi.org/10.1271/bbb.70464
  4. Hwang JH, Yu KW, Lee KH, Lee SR, Kim MK. Immunostimulating and anticancer extracts from mixture of herbal medicines. Korea patent 10-0766388 (2007)
  5. Yi JM, Kim MS, Seo SW, Lee KN, Yook CS, Kim HM. Acanthopanax senticosus root inhibits mast cell dependent anaphylaxis. Clin. Chim. Acta 312: 163-168 (2001) https://doi.org/10.1016/S0009-8981(01)00613-1
  6. Matsui S, Matsumoto H, Sonoda Y, Ando K, Aizu-Yokota E, Sato T. Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. Int. Immunopharmacol. 4: 1633-1644 (2004) https://doi.org/10.1016/j.intimp.2004.07.023
  7. Rafi MM, Vastano BC. Identification of a structure specific Bcl-2 phosphorylating homoisoflavone molecule from Vietnamese coriander (Polygonatum odoratum) that induces apoptosis and G2/M cell cycle arrest in breast cancer cell lines. Food Chem. 104: 332-340 (2007) https://doi.org/10.1016/j.foodchem.2006.11.045
  8. Ha ES, Hwang SH, Shin KS, Yu KW, Lee KH, Choi JS, Park WM, Yoon TJ. Anti-metastatic activity of glycoprotein fractionated from Acanthopanax senticosus, involvement of NK-cell and macrophage activation. Arch. Pharm. Res. 27: 217-224 (2004) https://doi.org/10.1007/BF02980109
  9. Cheng A, Wan F, Wang J, Jin Z, Xu X. Macrophage immunomodulatory activity of polysaccharides isolated from Glycyrrhiza uralensis fish. Int. Immunopharmacol. 8: 43-50 (2008) https://doi.org/10.1016/j.intimp.2007.10.006
  10. Yamada H, Kiyohara H, Cyong JC. Takamoto N, Komatsu Y, Kawamura H, Aburada M, Hosoya E. Fractionation and characterization of mitogenic and anti-complementary active fraction from kampo (Japanese herbal) medicine 'Juzen-Taiho-To'. Planta Med. 56: 386-391 (1990) https://doi.org/10.1055/s-2006-960990
  11. Oka H, Ohno N, Iwanaga S, Izumi S, Kawakita T, Nomoto K, Yadomae T. Characterization of mitogenic substances in the hot-water extracts of Bupeuri Radix. Biol. Pharm. Bull. 18: 757-765 (1995) https://doi.org/10.1248/bpb.18.757
  12. Dubois M, Gilles KA, Hamilton JK, Rebers RA, Smith F. Colorimetric method for determination of sugars and related substances. Anal. Chem. 28: 350-356 (1956) https://doi.org/10.1021/ac60111a017
  13. Blumenkrantz N, Asboe-Hansen G. New method for quantitative determination of uronic acid. Anal. Biochem. 54: 484-489 (1973) https://doi.org/10.1016/0003-2697(73)90377-1
  14. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248-254 (1976) https://doi.org/10.1016/0003-2697(76)90527-3
  15. Johnes TM, Albersheim P. A gas chromatographic method for the determination of aldose and uronic acid constituents of plant cell wall polysaccharide. Plant Physiol. 49: 926-936 (1972) https://doi.org/10.1104/pp.49.6.926
  16. Zhao JF, Kiyohara H, Yamada H, Takemoto N, Kawamura H. Heterogeneity and characterization of mitogenic and anticomplementary pectic polysaccharides from the roots of Glycyrrhiza uralensis Fisch et D.C. Carbohyd. Res. 219: 149-172 (1991) https://doi.org/10.1016/0008-6215(91)89049-L
  17. Hong T, Matsumoto T, Kiyohara H, Yamada H. Enhanced production of hematopoietic growth factors through T cell activation in Peyer's patches by oral administration of kampo (Japanese herbal) medicine 'Juzen-Taiho-To'. Phytomedicine 5: 163-168 (1998)
  18. Page B, Page M, Noel C. A new fluorometric assay for cytotoxicity measurements in vitro. Int. J. Oncol. 3: 473-476 (1993)
  19. Yoon TJ, Yoo YC, Kang TB, Baek YJ, Song SK, Lee KH, Azuma I, Kim JB. Prophylactic effect of Korean mistletoe (Viscum album coloratum) extract on tumor metastasis is mediated by enhancement of NK cell activity. Int. J. Immunopharmacol. 20: 163-172 (1998) https://doi.org/10.1016/S0192-0561(98)00024-1
  20. Yoo YC, Watanabe S, Watanabe R, Hata K, Shimazaki K, Azuma I. Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice. Jpn. J. Cancer Res. 88:184-190 (1997) https://doi.org/10.1111/j.1349-7006.1997.tb00364.x
  21. Wei G, Zheng X. A survey of the studies on compatible law of ingredients in Chinese herbal prescriptions. J. Tradit. Chin. Med. 28:223-227 (2008) https://doi.org/10.1016/S0254-6272(08)60051-5
  22. Aspinall GO. Carbohydrate polymers of plant cell walls. pp. 95-115. In: Biogenesis of Plant Cell Wall Polysaccharides. Loewus F (ed). Academic Press, New York, NY, USA (1973)
  23. Clarke AE, Anderson RL, Stone BA. Form and function of arabinogalactans and arabinogalactan-proteins. Phytochemistry 18:521-540 (1979) https://doi.org/10.1016/S0031-9422(00)84255-7
  24. Kiyohara H, Yamada H. Structure of an anti-complementary arabinogalactan from the root of Angelica acutiloba Kitagawa. Carbohyd. Res. 193: 173-192 (1989) https://doi.org/10.1016/0008-6215(89)85117-1
  25. James SP, Zeitz M. Human gastrointestinal mucosal T cells. pp. 275-285. In: Handbook of Mucosal Immunology. Pearay LO, Jiri M, Michael EL, Warren S, Jerry RM, John B (eds). Academic Press, London, Great Britan (1994)
  26. Lee KH, Hwang JH, Yu KW. Preparation of kimchi supplemented with immunomodulatory components isolated from licorice. Food Sci. Biotechnol. 12: 351-357 (2003)
  27. Iigo M, Kuhara T, Ushida Y, Sekine K, Moore MA, Tsuda U. Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastatic in mice. Clin. Exp. Metastasis 17: 35-40 (1999)
  28. Shin SM, Hong ST. Acanthopanax and Platycodi independently prevents the onset of high fat diet induced hyperglyceridemia and obesity in C57BL/6 mice. Food Sci. Biotechnol. 14: 841-846 (2005)
  29. Wang D, Kandimalla ER, Yu D, Tang JX, Agrawal S. Oral administration of second-generation immunomodulatory oligonucleotides induces mucosal Th1 immune responses and adjuvant activity. Vaccine 23: 2614-2622 (2005) https://doi.org/10.1016/j.vaccine.2004.11.028
  30. Yoo YC, Saiki I, Sato K, Azuma I. MDP-Lys(L18), a lipophilic derivative of muramyl dipeptide, inhibits the metastasis of haematogenous and non-haematogenous tumors in mice. Vaccine 12: 175-180 (1994) https://doi.org/10.1016/0264-410X(94)90057-4