Ginsenosides from Panax ginseng Differentially Regulate Lymphocyte Proliferation

Abstract

We have examined the immunosuppressive effects of representative ginsenosides (Rb₁, Rb₂, Re and Rg₁) from Panax ginseng C. A. Meyer on CD4+ and CD8+ lymphocyte proliferation. Ginsenosides differentially modulated lymphocyte proliferation induced by concanavalin A (Con A), lipopolysaccharide (LPS), phytohemaglutinin (PHA) and interleukin-2 (IL-2). Thus, Rb₁ and Re significantly enhanced Con A-induced lymphocyte proliferation, whereas Rg₁ did not affect the proliferation. Interestingly, however, Rb₂ strongly blocked Con A, LPS and PHA-induced lymphocyte proliferation with the IC₅₀ values of 21.8, 29.0 and 24.0 μM, respectively. Moreover, Rb₂ inhibited Con A-stimulated IL-2 production with an IC₅₀ of 13.3 μM. In the IL-2-stimulated CD8+ T cell (CTLL-2) proliferation assay, Re and Rg₁ showed strong suppressive effects with IC₅₀ values of 57.5 and 64.7 μM, respectively. In contrast, neither Rb₁ nor Rb₂ did inhibit CTLL-2 cell proliferation at tested concentrations. These results suggest that ginsenosides from P. ginseng may modulate lymphocyte proliferation in a different manner.

Panax ginseng - Araliaceae - ginsenosides - interleukin-2 - lymphocyte proliferation

References

• 1 Panayi G S, Lanchbury J S, Kingsley G H. The importance of the T-cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis.  Arth Rheumatol. 1992;  35 729-35
• 2 Correll P H, Iwama A, Tondat S, Mayrhofer G, Suda T, Bernstein A. Deregulated inflammatory response in mice lacking the STK/RON receptor tyrosine kinase.  Genes Funct. 1997;  1 69-83
• 3 Murphy K M. T lymphocyte differentiation in the periphery.  Curr Opin Immunol. 1998;  10 226-32
• 4 Weinstein S L, Sanghera J S, Lemke K, DeFranco A, Pelech C L. Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages.  J Biol Chem. 1992;  267 14 955-62
• 5 Geng Y, Marier R, Lotz M. Tyrosine kinases are involved with the expression of inducible nitric oxide synthase in human articular chondrocytes.  J Cell Physiol. 1995;  163 545-54
• 6 Gillis C N. Panax ginseng pharmacology: a nitric oxide link?.  Biochem Pharmacol. 1997;  54 1-8
• 7 Matsuda H, Samukawa K, Kubo M. Anti-inflammatory activity of ginsenoside Ro.  Planta Med. 1989;  56 19-23
• 8 Kenarova B, Neychev H, Hadjiivanova C, Petkov V D. Immunomodulationg activity of ginsenoside Rg₁ from Panax ginseng .  Jpn J Pharmacol. 1990;  54 447-54
• 9 Mochizuki M, Yoo Y C, Matsuzawa K, Sato K, Saiki I, Tono-oka S. et al . et alInhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb_2, 20(R)- and 20(S)-ginsenoside-Rg₃, of red ginseng.  Biol Pharm Bull. 1995;  18 1197-202
• 10 Cho J Y, Park J, Yoo E S, Baik K U, Park M H. Effect of ginseng saponin on tumor necrosis factor-α production and T cell proliferation.  Yakhak Hoeji. 1998;  43 296-301
• 11 Cho J Y, Yoo E S, Baik K U, Park M H. Han BH. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-α production and its modulation by known TNF-α antagonists.  Planta Med. 2001;  67 213-8
• 12 Cho J Y, Kim P S, Park J, Chae S H, Yoo E S, Baik K U. et al . Immunomodulatory effect of arctigenin on TNF-α  and NO production, and lymphocyte proliferation.  J Pharm Pharmacol. 1999;  51 1267-73
• 13 Sekut L, Connolly K M. Pathophysiology and regulation of TNF-α in inflammation.  Drug News Perspect. 1996;  9 261-9
• 14 Cho J Y, Baik K U, Yoshikawa K, Park M H. In vitro anti-inflammatory effects of woorenosides from the rhizomes of Coptis japonica var. dissecta.  J Nat Prod. 2000;  63 1205-9
• 15 Cho J Y, Kim A R, Park J S, Yoo E S, Park M H. Lignans from Coptis japonica differentially acts as anti-inflammatory principles.  Planta Med. 2001;  67 312-6
• 16 Cho J Y, Kim P S, Park J, Chae S, Yoo E S, Baik K U. et al . Savinin a lignan from Pterocarpus santalinus as an active anti-inflammatory principle.  Biol Pharm Bull. 2001;  24 167-71
• 17 Cho J Y, Yoo E S, Baik K U, Jung J H, Hong S Y, Park M H. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa .  Eur J Pharmacol. 2000;  398 399-407
• 18 Waldmann T, Tagaya Y, Bamford R. Interleukin-2, interleukin-15, and their receptors.  Int Rev Immunol. 1998;  16 205-26
• 19 Sinha B, Semmler J, Eisenhut T, Eigler A, Endres S. Enhanced tumor necrosis factor suppression and cyclic adenosine monophosphate accumulation by combination of phosphodiesterase inhibitors and prostanoids.  Eur J Immunol. 1996;  25 147-53
• 20 Nikaido T, Ohmoto T, Sankawa U, Tanaka O, Kasai R, Shoji J. et al . Inhibition of cyclic AMP phosphodiesterase in Panax ginseng C. A. Meyer and Panax japonicus C. A. Meyer.  Chem Pharm Bull. 1984;  32 1477-83
• 21 Plohmann B, Bader G, Hiller K, Franz G. Immunomodulatory and antitumoral effects of triterpenoid saponins.  Pharmazie. 1997;  52 953-7