DOI QR코드

DOI QR Code

Rhei Rhizoma Extracts Have Antiproliferative Properties and Differential Effects on NO Production in Macrophages

  • Pyo, Suh-Kneung (College of Pharmacy, Sungkyunkwan University) ;
  • Son, Eun-Wha (Department of Pharmacognosy Material Development, Kangwon National University)
  • Published : 2006.12.01

Abstract

Recently, Rhei Rhizoma extracts (RRE) have begun to receive more attention as potential biological response modifiers. In the present study, we studied the antiproliferative effect of RRE on tumor cells and the effect of RRE on macrophage function. A variety of tumor cells and macrophages were treated with RRE at various concentrations. The effect of RRE on cell proliferation was measured by MTT assay and the effect of RRE on the production of nitric oxide (NO) was determined in the macrophage-like cell lines Raw264.7, C6 and peritoneal macrophages (pMQ). RRE inhibited the growth of tumor cells (e.g., B16, HOS). However, the effects of RRE on the production of NO varied with macrophage types. RRE had no effect on C6 cell growth and slightly increased the growth of Raw264.7 cells. In addition, treatment of normal pMQ with RRE enhanced NO production in a concentration-dependent manner, whereas RRE suppressed NO production at $50\;{\mu}g/mL$ in both Raw264.7 and C6 cells. However, RRE suppressed NO production in LPS/IFN-$\gamma$-stimulated C6 cells. Overall, these results suggest that RRE elicits an antiproliferative property and differentially modulates NO production in various macrophages, and have a potential for therapeutic application.

References

  1. Torrence PF. 1985. Biological Response Modifiers. Academic Press Inc, p 1-6
  2. Giaccone G, Schilsky R, Sondel P. 2001. Cancer chemotherapy and biological response modifiers. Elsevier, Amsterdam, Netherlands. Vol 19
  3. Hahn H, Kaufmann SH. 1981. The role of cell-mediated immunity in bacterial infections. Rev Infect Dis 3: 1221-1250 https://doi.org/10.1093/clinids/3.6.1221
  4. Verstovsek S, Maccubbin D, Ehrke MJ, Mihich E. 1992. Tumoricidal activation of murine resident peritoneal macrophages by interleukin 2 and tumor necrosis factor alpha. Cancer Res 52: 3880-3885
  5. Nathan CF. 1987. Secretory products of macrophages. J Clin Invest 79: 319-326 https://doi.org/10.1172/JCI112815
  6. Adams DO, Hamilton TA. 1984. The cell biology of macrophage activation. Annu Rev Immunol 2: 283-318 https://doi.org/10.1146/annurev.iy.02.040184.001435
  7. Keller R, Keist R. 1989. Abilities of activated macrophages to manifest tumoricidal activity and to generate reactive nitrogen intermediates: a comparative study in vitro and ex vivo. Biochem Biophys Res Commun 164: 968-973 https://doi.org/10.1016/0006-291X(89)91764-6
  8. Bredt DS, Snyder SH. 1994. Nitric oxide: a physiologic messenger molecule. Annu Rev Biochem 63: 175-195 https://doi.org/10.1146/annurev.bi.63.070194.001135
  9. Kim YS, Jung EA, Shin JE, Chang JC, Yang HK, Kim NJ, Cho KH, Bae HS, Moon SK, Kim DH. 2002. Daio- Orengedokuto inhibits HMG-CoA reductase and pancreatic lipase. Biol Pharm Bull 25: 1442-1445 https://doi.org/10.1248/bpb.25.1442
  10. Park EK, Choo MK, Yoon HK, Kim DH. 2002. Antithrombotic and antiallergic activities of rhaponticin from Rhei Rhizoma are activated by human intestinal bacteria. Arch Pharm Res 25: 528-533 https://doi.org/10.1007/BF02976613
  11. Matsuda H, Tomohiro N, Hiraba K, Harima S, Ko S, Matsuo K, Yoshikawa M, Kubo M. 2001. Study on anti-Oketsu activity of rhubarb II. Anti-allergic effects of stilbene components from Rhei undulati Rhizoma (dried rhizoma of Rheum undulatum cultivated in Korea). Biol Pharm Bull 24: 264-267 https://doi.org/10.1248/bpb.24.264
  12. Jin H, Sakaida I, Tsuchiya M, Okita K. 2005. Herbal medicine Rhei rhizome prevents liver fibrosis in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. Life Sci 76: 2805-2816 https://doi.org/10.1016/j.lfs.2004.09.041
  13. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63 https://doi.org/10.1016/0022-1759(83)90303-4
  14. Ding AH, Nathan CF, Stuer DJ. 1988. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol 141: 2407-2412
  15. Ra MS, Chin J, Cho N. 2000. Cytotoxicity ok crude extracts of Rheum undulatum L. with Human kidney epithelial cell A498. Korean J Food Nutr 13: 460-464
  16. Keller R, Keist R. 1989. Abilities of activated macrophages to manifest tumoricidal activity and to generate reactive nitrogen intermediates: a comparative study in vitro and ex vivo. Biochem Biophys Res Commun 164: 968- 973 https://doi.org/10.1016/0006-291X(89)91764-6
  17. Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM. 1988 Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157: 87-94 https://doi.org/10.1016/S0006-291X(88)80015-9
  18. Nathan CF. 1987. Secretory products of macrophages. J Clin Invest 79: 319-326 https://doi.org/10.1172/JCI112815
  19. Stebbing AR. 1982. Hormesis-the stimulation of growth by low levels of inhibitiors. Sci Total Environ 22: 213- 234 https://doi.org/10.1016/0048-9697(82)90066-3
  20. Dringen R. 2005. Oxidative and antioxidative potential of brain microglial cells. Antioxid Redox Signal 7: 1223- 1233 https://doi.org/10.1089/ars.2005.7.1223