Archives of Pharmacal Research

, Volume 32, Issue 6, pp 813–822 | Cite as

Inhibitory effect of saponin fraction from Codonopsis lanceolata on immune cell-mediated inflammatory responses

  • Se Eun Byeon
  • Wahn Soo Choi
  • Eock Kee Hong
  • Jaehwi Lee
  • Man Hee Rhee
  • Hwa-Jin Park
  • Jae Youl Cho
Research Articles Drug Discovery and Development


Saponin components are known to be pharmaceutically, cosmetically and nutraceutically valuable principles found in various herbal medicine. In this study, we evaluated the inhibitory role of saponin fraction (SF), prepared from C. lanceolata, an ethnopharmacologically famous plant, on various inflammatory responses managed by monocytes, macrophages, lymphocytes and mast cells. SF clearly suppressed the release of nitric oxide (NO) and tumor necrosis factor (TNF)-α, but not prostaglandin E2 (PGE2). While this fraction did not scavenge the reactivity of SNP-induced radicals in RAW264. 7 cells, it negatively modulated the phagocytic uptake of macrophages treated with FITC-dextran. Interestingly, SF completely diminished cell-cell adhesion events induced by both CD29 and CD43, but not cell-fibronectin adhesion. Concanavalin (Con) A [as well phytohemaglutinin A (PHA)]-induced proliferation of splenic lymphocytes as well as interferon (IFN)-γ production were also clearly suppressed by SF treatment. Finally, SF also significantly blocked the degranulation process of mast cell line RBL-2H3 cell as assessed by DNP-BSA-induced β-hexosaminidase activity. The anti-inflammatory activities of SF on NO production seemed to be due to inhibition of nuclear factor (NF)-κB activation signaling, since it blocked the phosphorylation of inhibitor of κB (IκB)α as well as inducible NO synthase (iNOS) expression. Therefore, these results suggest that SF may be considered as a promising herbal medicine with potent anti-inflammatory actions.

Key words

Codonopsis lanceolata Saponin fraction Anti-inflammatory effects Inflammatory responses Inflammatory cells 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Berg, J., Fellier, H., Christoph, T., Grarup, J., and Stimmeder, D., The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm. Res., 48, 369–379 (1999).PubMedCrossRefGoogle Scholar
  2. Bradford, M. M., 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).PubMedCrossRefGoogle Scholar
  3. Byeon, S. E., Chung, J. Y., Lee, Y. G., Kim, B. H., Kim, K. H., and Cho, J. Y., In vitro and in vivo anti-inflammatory effects of taheebo, a water extract from the inner bark of Tabebuia avellanedae. J. Ethnopharmacol., 119, 145–152 (2008).PubMedCrossRefGoogle Scholar
  4. Cherayil, B. J. and Antos, D., Inducible nitric oxide synthase and Salmonella infection. Microbes Infect., 3, 771–776 (2001).PubMedCrossRefGoogle Scholar
  5. Cho, J. Y., Baik, K. U., Jung, J. H., and Park, M. H., In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur. J. Pharmacol., 398, 399–407 (2000).PubMedCrossRefGoogle Scholar
  6. Cho, J. Y., Chain, B. M., Vives, J., Horejsi, V., and Katz, D. R., Regulation of CD43-induced U937 homotypic aggregation. Exp. Cell Res., 290, 155–167 (2003a).PubMedCrossRefGoogle Scholar
  7. Cho, J. Y., Fox, D. A., Horejsi, V., Sagawa, K., Skubitz, K. M., Katz, D. R., and Chain, B., The functional interactions between CD98, beta1-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood, 98, 374–382 (2001).PubMedCrossRefGoogle Scholar
  8. Cho, J. Y., Skubitz, K. M., Katz, D. R., and Chain, B. M., CD98-dependent homotypic aggregation is associated with translocation of protein kinase Cdelta and activation of mitogen-activated protein kinases. Exp. Cell Res., 286, 1–11 (2003b).PubMedCrossRefGoogle Scholar
  9. Choo, M. K., Sakurai, H., Kim, D. H., and Saiki, I., A ginseng saponin metabolite suppresses tumor necrosis factor-alpha-promoted metastasis by suppressing nuclear factor-kappaB signaling in murine colon cancer cells. Oncol. Rep., 19, 595–600 (2008).PubMedGoogle Scholar
  10. Cieslik, K., Zhu, Y., and Wu, K. K., Salicylate suppresses macrophage nitric-oxide synthase-2 and cyclo-oxygenase-2 expression by inhibiting CCAAT/enhancer-binding protein-beta binding via a common signaling pathway. J. Biol. Chem., 277, 49304–49310 (2002).PubMedCrossRefGoogle Scholar
  11. Duperrier, K., Eljaafari, A., Dezutter-Dambuyant, C., Bardin, C., Jacquet, C., Yoneda, K., Schmitt, D., Gebuhrer, L., and Rigal, D., Distinct subsets of dendritic cells resembling dermal DCs can be generated in vitro from monocytes, in the presence of different serum supplements. J. Immunol. Methods, 238, 119–131 (2000).PubMedCrossRefGoogle Scholar
  12. Fratkin, M. J., Sharpe, A. R., Jr., and Hirsch, J. I., Letter: Gallium scanning and inflammatory lesions. Ann. Intern. Med., 80, 114–115 (1974).PubMedGoogle Scholar
  13. Fujiwara, N. and Kobayashi, K., Macrophages in inflammation. Curr. Drug Targets. Inflamm. Allergy, 4, 281–286 (2005).PubMedCrossRefGoogle Scholar
  14. Guclu-Ustundag, O. and Mazza, G., Saponins: properties, applications and processing. Crit. Rev. Food Sci. Nutr., 47, 231–258 (2007).PubMedCrossRefGoogle Scholar
  15. Hur, G. Y., Choi, G. S., Park, H. J., Ye, Y. M., and Park, H. S., Anaphylactic shock induced by Codonopsis lanceolata, traditional Chinese medicine in a patient with allergic rhinitis. Allergy, 63, 1406–1407 (2008).PubMedCrossRefGoogle Scholar
  16. Kim, B. H., Lee, Y. G., Park, T. Y., Kim, H. B., Rhee, M. H., and Cho, J. Y., Ginsenoside Rp1, a Ginsenoside Derivative, Blocks Lipopolysaccharide-Induced Interleukin-1beta Production via Suppression of the NF-kappaB Pathway. Planta Med., (2009).Google Scholar
  17. Kim, H. S., Lee, E. H., Ko, S. R., Choi, K. J., Park, J. H., and Im, D. S., Effects of ginsenosides Rg3 and Rh2 on the proliferation of prostate cancer cells. Arch. Pharm. Res., 27, 429–435 (2004).PubMedCrossRefGoogle Scholar
  18. Kim, M. O., Moon, D. O., Choi, Y. H., Lee, J. D., Kim, N. D., and Kim, G. Y., Platycodin D induces mitotic arrest in vitro, leading to endoreduplication, inhibition of proliferation and apoptosis in leukemia cells. Int. J. Cancer, 122, 2674–2681 (2008).PubMedCrossRefGoogle Scholar
  19. Larrucea, S., Gonzalez-Rubio, C., Cambronero, R., Ballou, B., Bonay, P., Lopez-Granados, E., Bouvet, P., Fontan, G., Fresno, M., and Lopez-Trascasa, M., Cellular adhesion mediated by factor J, a complement inhibitor. Evidence for nucleolin involvement. J. Biol. Chem., 273, 31718–31725 (1998).PubMedCrossRefGoogle Scholar
  20. Lee, J. H., Seo, J. Y., Ko, N. Y., Chang, S. H., Her, E., Park, T., Lee, H. Y., Han, J. W., Kim, Y. M., and Choi, W. S., Inhibitory activity of Chrysanthemi sibirici herba extract on RBL-2H3 mast cells and compound 48/80-induced anaphylaxis. J. Ethnopharmacol., 95, 425–430 (2004).PubMedCrossRefGoogle Scholar
  21. Lee, K. T., Choi, J., Jung, W. T., Nam, J. H., Jung, H. J., and Park, H. J., Structure of a new echinocystic acid bisdesmoside isolated from Codonopsis lanceolata roots and the cytotoxic activity of prosapogenins. J. Agric. Food Chem., 50, 4190–4193 (2002).PubMedCrossRefGoogle Scholar
  22. Lee, Y. G., Byeon, S. E., Kim, J. Y., Lee, J. Y., Rhee, M. H., Hong, S., Wu, J. C., Lee, H. S., Kim, M. J., Cho, D. H., and Cho, J. Y., Immunomodulatory effect of Hibiscus cannabinus extract on macrophage functions. J. Ethnopharmacol., 113, 62–71 (2007a).PubMedCrossRefGoogle Scholar
  23. Lee, Y. G., Kim, J. Y., Lee, J. Y., Byeon, S. E., Hong, E. K., Lee, J., Rhee, M. H., Park, H. J., and Cho, J. Y., Regulatory effects of Codonopsis lanceolata on macrophage-mediated immune responses. J. Ethnopharmacol., 112, 180–188 (2007b).PubMedCrossRefGoogle Scholar
  24. Lee, Y. G., Lee, W. M., Kim, J. Y., Lee, J. Y., Lee, I. K., Yun, B. S., Rhee, M. H., and Cho, J. Y., Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells. Br. J. Pharmacol., 154, 852–863 (2008).PubMedCrossRefGoogle Scholar
  25. Li, J. P., Liang, Z. M., and Yuan, Z., Triterpenoid saponins and anti-inflammatory activity of Codonopsis lanceolata. Pharmazie, 62, 463–466 (2007).PubMedGoogle Scholar
  26. Nah, S. Y., Kim, D. H., and Rhim, H., Ginsenosides: are any of them candidates for drugs acting on the central nervous system? CNS Drug Rev., 13, 381–404 (2007).PubMedGoogle Scholar
  27. Naumann, M., Nuclear factor-kappa B activation and innate immune response in microbial pathogen infection. Biochem. Pharmacol., 60, 1109–1114 (2000).PubMedCrossRefGoogle Scholar
  28. Newman, S. L., Macrophages in host defense against Histoplasma capsulatum. Trends. Microbiol., 7, 67–71 (1999).PubMedCrossRefGoogle Scholar
  29. Pulla, R. K., Kim, Y. J., M. K., Senthil, K. S., In, J. G., and Yang, D. C., Isolation of a novel dehydrin gene from Codonopsis lanceolata and analysis of its response to abiotic stresses. BMB Rep., 41, 338–343 (2008).PubMedGoogle Scholar
  30. Rajapakse, N., Kim, M. M., Mendis, E., and Kim, S. K., Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW264.7 cells by carboxybutyrylated glucosamine takes place via down-regulation of mitogen-activated protein kinasemediated nuclear factor-kappaB signaling. Immunology, 123, 348–357 (2008).PubMedCrossRefGoogle Scholar
  31. Raso, G. M., Pacilio, M., Di Carlo, G., Esposito, E., Pinto, L., and Meli, R., In-vivo and in-vitro anti-inflammatory effect of Echinacea purpurea and Hypericum perforatum. J. Pharm. Pharmacol., 54, 1379–1383 (2002).PubMedCrossRefGoogle Scholar
  32. Sheu, M. L., Chao, K. F., Sung, Y. J., Lin, W. W., Lin-Shiau, S. Y., and Liu, S. H., Activation of phosphoinositide 3-kinase in response to inflammation and nitric oxide leads to the up-regulation of cyclooxygenase-2 expression and subsequent cell proliferation in mesangial cells. Cell. Signal., 17, 975–984 (2005).PubMedCrossRefGoogle Scholar
  33. Shiloh, M. U. and Nathan, C. F., Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria. Curr. Opin. Microbiol., 3, 35–42 (2000).PubMedCrossRefGoogle Scholar
  34. Song, H. J., Shin, C. Y., Oh, T. Y., and Sohn, U. D., The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK. J. Ethnopharmacol., 118, 94–101 (2008).PubMedCrossRefGoogle Scholar
  35. Speroni, E., Cervellati, R., Costa, S., Dall’Acqua, S., Guerra, M. C., Panizzolo, C., Utan, A., and Innocenti, G., Analgesic and antiinflammatory activity of Cyclamen repandum S. et S. Phytother. Res., 21, 684–689 (2007).PubMedCrossRefGoogle Scholar
  36. Stafford, J. L., Neumann, N. F., and Belosevic, M., Macrophage-mediated innate host defense against protozoan parasites. Crit. Rev. Microbiol., 28, 187–248 (2002).PubMedCrossRefGoogle Scholar
  37. Suh, S. J., Jin, U. H., Kim, K. W., Son, J. K., Lee, S. H., Son, K. H., Chang, H. W., Lee, Y. C., and Kim, C. H., Triterpenoid saponin, oleanolic acid 3-O-beta-d-glucopyranosyl (1→3)-alpha-l-rhamnopyranosyl(1→2)-alpha-l-ar abinopyranoside (OA) from Aralia elata inhibits LPS-induced nitric oxide production by down-regulated NF-kappaB in raw 264.7 cells. Arch. Biochem. Biophys., 467, 227–233 (2007).PubMedCrossRefGoogle Scholar
  38. Ushijima, M., Komoto, N., Sugizono, Y., Mizuno, I., Sumihiro, M., Ichikawa, M., Hayama, M., Kawahara, N., Nakane, T., Shirota, O., Sekita, S., and Kuroyanagi, M., Triterpene glycosides from the roots of Codonopsis lanceolata. Chem. Pharm. Bull. (Tokyo), 56, 308–314 (2008).CrossRefGoogle Scholar
  39. Xu, L. P., Wang, H., and Yuan, Z., Triterpenoid saponins with anti-inflammatory activity from Codonopsis lanceolata. Planta Med., 74, 1412–1415 (2008).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2009

Authors and Affiliations

  • Se Eun Byeon
    • 1
  • Wahn Soo Choi
    • 2
  • Eock Kee Hong
    • 3
  • Jaehwi Lee
    • 4
  • Man Hee Rhee
    • 5
  • Hwa-Jin Park
    • 6
  • Jae Youl Cho
    • 1
  1. 1.School of Bioscience and Biotechnology, and Institute of Bioscience and BiotechnologyKangwon National UniversityChuncheonKorea
  2. 2.College of MedicineKunkuk UniversityChungjuKorea
  3. 3.Department of Bioengineering and TechnologyKangwon National UniversityChuncheonKorea
  4. 4.College of PharmacyChung-Ang UniversitySeoulKorea
  5. 5.Laboratory of Veterinary Physiology & Signaling, College of Veterinary MedicineKyungpook National UniversityDaeguKorea
  6. 6.Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research CenterInje UniversityGimhaeKorea

Personalised recommendations