Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
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).
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).
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).
Cherayil, B. J. and Antos, D., Inducible nitric oxide synthase and Salmonella infection. Microbes Infect., 3, 771–776 (2001).
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).
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).
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).
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).
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).
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).
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).
Fratkin, M. J., Sharpe, A. R., Jr., and Hirsch, J. I., Letter: Gallium scanning and inflammatory lesions. Ann. Intern. Med., 80, 114–115 (1974).
Fujiwara, N. and Kobayashi, K., Macrophages in inflammation. Curr. Drug Targets. Inflamm. Allergy, 4, 281–286 (2005).
Guclu-Ustundag, O. and Mazza, G., Saponins: properties, applications and processing. Crit. Rev. Food Sci. Nutr., 47, 231–258 (2007).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Li, J. P., Liang, Z. M., and Yuan, Z., Triterpenoid saponins and anti-inflammatory activity of Codonopsis lanceolata. Pharmazie, 62, 463–466 (2007).
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).
Naumann, M., Nuclear factor-kappa B activation and innate immune response in microbial pathogen infection. Biochem. Pharmacol., 60, 1109–1114 (2000).
Newman, S. L., Macrophages in host defense against Histoplasma capsulatum. Trends. Microbiol., 7, 67–71 (1999).
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).
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).
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).
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).
Shiloh, M. U. and Nathan, C. F., Reactive nitrogen intermediates and the pathogenesis of Salmonella and mycobacteria. Curr. Opin. Microbiol., 3, 35–42 (2000).
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).
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).
Stafford, J. L., Neumann, N. F., and Belosevic, M., Macrophage-mediated innate host defense against protozoan parasites. Crit. Rev. Microbiol., 28, 187–248 (2002).
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).
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).
Xu, L. P., Wang, H., and Yuan, Z., Triterpenoid saponins with anti-inflammatory activity from Codonopsis lanceolata. Planta Med., 74, 1412–1415 (2008).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Byeon, S.E., Choi, W.S., Hong, E.K. et al. Inhibitory effect of saponin fraction from Codonopsis lanceolata on immune cell-mediated inflammatory responses. Arch. Pharm. Res. 32, 813–822 (2009). https://doi.org/10.1007/s12272-009-1601-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-009-1601-7