Flower MeOH Extract of Panax Notoginseng Attenuates the Production of Nitric Oxide and Pro-inflammatory Cytokines in LPS-stimulated RA W264.7 Cells

삼칠화(三七花)의 대식세포로부터 LPS에 의해 유도되는 nitric oxide와 전염중성 사이토카인의 생성 억제효과

  • Joo, Ye-Jin (Dept. of Oriental Internal Medicine, College of Oriental Medicine, Dongguk University) ;
  • Jung, Hye-Mi (Dept. of Oriental Internal Medicine, College of Oriental Medicine, Dongguk University) ;
  • Seo, Un-Kyo (Dept. of Oriental Internal Medicine, College of Oriental Medicine, Dongguk University)
  • 주예진 (동국대학교 한의과대학 내과학교실) ;
  • 정혜미 (동국대학교 한의과대학 내과학교실) ;
  • 서운교 (동국대학교 한의과대학 내과학교실)
  • Published : 2009.01.30


Objectives: Inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ playa critical role in inflammatory immune response. Therefore, intervention of inflammatory mediator production promises therapeutic benefit for treatment of many chronic inflammatory diseases, such as allergic asthma, rheumatoid arthritis, multiple sclerosis, septic shock and neurodegenerative diseases. In this study, the pharmacological effects of the flower MeOH extract Panax notoginseng (Notoginseng Flos; NF) on inflammation were investigated to address potential therapeutic or toxic effects. Methods: RA W264.7 cells were treated with different concentrations of NF methanol (NF-M) extract in the presence or absence of LPS ($1{\mu}g/m{\ell}$). Results: NF-M extract significantly inhibited LPS-induced production of NO, $PGE_2$ and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in a dose-dependent manner. In addition, NF-M extract suppressed mRNA expressions and protein levels of iNOS, COX-2 and pro-inflammatory cytokines in LPS-stimulated RA W264.7 cells. Conclusion: These results indicated that NF-M extract inhibits LPS-induced production of inflammatory mediators in macrophages and demonstrated that NF-M extract possesses anti-inflammatory properties in vitro.


  1. Bosca L, Zeini M, Través PG, Hortelano S. Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology. 2005;208(2):249-58. https://doi.org/10.1016/j.tox.2004.11.035
  2. Moncada S. Nitric oxide: discovery and impact on clinical medicine. Journal of the Royal Society of Medicine. 1999;92(4):164-9.
  3. Nathan C. Nitric oxide as a secretory product of mammalian cells. The FASEB journal. 1992;6(12):3051-64.
  4. Turini ME, DuBois RN. Cyclooxygenase-2: a therapeutic target. Annual review of medicine. 2002;53:35-57. https://doi.org/10.1146/annurev.med.53.082901.103952
  5. Rocca B, FitzGerald GA. Cyclooxygenases and prostaglandins: shaping up the immune response. International immunopharmacology. 2002;2(5):603-30. https://doi.org/10.1016/S1567-5769(01)00204-1
  6. Andreakos E, Foxwell B, Feldmann M. Is targeting Toll-like receptors and their signaling pathway a useful therapeutic approach to modulating cytokine-driven inflammation? Immunological reviews. 2004;202:250-65. https://doi.org/10.1111/j.0105-2896.2004.00202.x
  7. 李時珍, 本草綱目. 北京;人民衛生出版社. 1982:767-8.
  8. 黃宮繡, 本草求眞. 台北;宏業書局有限公司. 1981:236.
  9. 박창국, 이상일, 삼칠근이 TAA 中毒白鼠의 刊損傷에 미치는 影響. 동서의학. 1989;14(1):35-53.
  10. Wei Y, Fan JM, Pan LP. Effect of Panax notoginseng saponins on human kidney fibroblast. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2002;22(1):47-9. Chinese.
  11. Park KM, Kim YS, Jeong TC, Joe CO, Shin HJ, Lee YH, Nam KY, Park JD. Nitric oxide is involved in the immunomodulating activities of acidic polysaccharide from Panax ginseng. Planta medica. 2001;67(2):122-6. https://doi.org/10.1055/s-2001-11508
  12. Rhule A, Navarro S, Smith JR, Shepherd DM. Panax notoginseng attenuates LPS-induced proinflammatory mediators in RAW264.7 cells. Journal of ethnopharmacology. 2006;106(1):121-8. https://doi.org/10.1016/j.jep.2005.12.012
  13. Wang CZ, Xie JT, Zhang B, Ni M, Fishbein A, Aung HH, Mehendale SR, Du W, He TC, Yuan CS. Chemopreventive effects of Panax notoginseng and its major constituents on SW480 human colorectal cancer cells. International journal of oncology. 2007;31(5):1149-56.
  14. Xu QF, Fang XL, Chen DF. Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. Journal of ethnopharmacology. 2003;84(2-3):187-92. https://doi.org/10.1016/S0378-8741(02)00317-3
  15. He W, Zhu Z, Liu J, Ye H, Zeng J, Huang X, Lai F. Study on therapeutic window of opportunity for Panax notoginseng saponins following focal cerebral ischemia/reperfusion injury in rats. Zhong Yao Cai. 2004;27(1):25-7.
  16. Sun K, Wang CS, Guo J, Horie Y, Fang SP, Wang F, Liu YY, Liu LY, Yang JY, Fan JY, Han JY. Protective effects of ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 on lipopolysaccharide-induced microcirculatory disturbance in rat mesentery. Life sciences. 2007; 81(6):509-18. https://doi.org/10.1016/j.lfs.2007.06.008
  17. Gao X, Dan M, Zhao A, Xie G, Jia W. Simultaneous determination of saponins in flower buds of Panax notoginseng using high performance liquid chromatography. Biomedical chromatography. 2008;22(3):244-9. https://doi.org/10.1002/bmc.915
  18. Wang CZ, Luo X, Zhang B, Song WX, Ni M, Mehendale S, Xie JT, Aung HH, He TC, Yuan CS. Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells. Cancer chemotherapy and pharmacology. 2007;60(1):69-79. https://doi.org/10.1007/s00280-006-0350-2
  19. Abreu MT, Arditi M. Innate immunity and toll-like receptors: clinical implications of basic science research. Jornal de pediatria. 2004;144(4):421-9.
  20. Hanada T, Yoshimura A. Regulation of cytokine signaling and inflammation. Cytokine & growth factor reviews. 2002;3(4-5):413-21.
  21. 張錫純. 醫學衷中參書錄. 서울:醫聖堂:1999:77.
  22. 한의과대학 본초학 편찬위원회. 본초학. 서울:영림사. 2007:440-1.
  23. Chang SH, Choi Y, Park JA, Jung DS, Shin J, Yang JH, Ko SY, Kim SW, Kim JK. Anti-inflammatory effects of BT-201, an n-butanol extract of Panax notoginseng, observed in vitro and in a collagen-induced arthritis model. Clinical nutrition. 2007;26(6):785-91. https://doi.org/10.1016/j.clnu.2007.07.008
  24. Assinewe VA, Amason JT, Aubry A, Mullin J, Lemaire I. Extractable polysaccharides of Panax quinquefolius L. (North American ginseng) root stimulate TNF-alpha production by alveolar macrophages. Phytomedicine. 2002;9(5):398-404. https://doi.org/10.1078/09447110260571625
  25. Jin UH, Park SG, Suh SJ, Kim JK, Kim DS, Moon SK, Lee YC, Park WH, Kim CH. Inhibitory effect of Panax notoginseng on nitric oxide synthase, cyclo-oxygenase-2 and neutrophil functions. Phytotherapy research. 2007;21(2):142-8. https://doi.org/10.1002/ptr.2018
  26. Park WH, Lee SK, Kim CH. A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats. Life Sciences. 2005;76(15):1675-90. https://doi.org/10.1016/j.lfs.2004.07.030
  27. Yang ZG, Sun HX, Ye YP. Ginsenoside Rd from Panax notoginseng is cytotoxic towards HeLa cancer cells and induces apoptosis. Chemistry & biodiversity. 2006;3(2):187-97. https://doi.org/10.1002/cbdv.200690022
  28. Li L, Sheng Y, Zhang J, Guo D. Determination of four active saponins of Panax notoginseng in rat feces by high-performance liquid chromatography. Journal of chromatographic science. 2005;43(8):421-5. https://doi.org/10.1093/chromsci/43.8.421
  29. Wan JB, Yang FQ, Li SP, Wang YT, Cui XM. Chemical characteristics for different parts of Panax notoginseng using pressurized liquid extraction and HPLC-ELSD. Journal of pharmaceutical and biomedical analysis. 2006;41(5):1596-601. https://doi.org/10.1016/j.jpba.2006.01.058
  30. Gao H, Wang F, Lien EJ, Trousdale MD. Immunostimulating polysaccharides from Panax notoginseng. Pharmaceutical research. 1996;13(8):1196-200. https://doi.org/10.1023/A:1016060119425
  31. Ng TB. Pharmacological activity of sanchi ginseng (Panax notoginseng). The Journal of pharmacy and pharmacology. 2006;58:1007-19. https://doi.org/10.1211/jpp.58.8.0001
  32. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cellular Signaling. 2001;13:85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  33. Raabe T, Bukrinsky M, Currie RA. Relative contribution of transcription and translation to the induction of tumor necrosis factor-alpha by lipopolysaccharide. The Journal of biological chemistry. 1998;273:974-80. https://doi.org/10.1074/jbc.273.2.974
  34. Komakine N, Okasaka M, Takaishi Y, kawazoe K, Murakami K, Yamada Y. New Dammarane-Type Saponin from Roots of Panax notoginseng. Natural Medicines. 2006;60:135-7. https://doi.org/10.1007/s11418-005-0016-0
  35. MJ Cho, SY Lee, JS Kim, JH Lee, HS Choi, HY Lee, HK Ha, CS Kim, SS Kang. Isolation of a cerebroside from Panax notoginseng. The Journal of Korean Society of Pharmacognogy. 2006;37(2):81-4.
  36. WR Lee, BY Pyun. Serum Level of TNF-alpha and Soluble TNF Receptor I in Infants with RDS and Their Significance as a Prospective Indicator for Development of Infantile Asthma. The Journal of Korean Academy of Pediatric Allergy and Respiratory Disease. 1999;9(3):280-9.
  37. Lampinen M, Carlson M, Håkansson LD, Venge P. Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy. 2004;59(8):793-805. https://doi.org/10.1111/j.1398-9995.2004.00469.x