In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists.
Ginsenosides are the major principles of Panax ginseng C. A. Meyer (Araliaceae) used as a mild oriental folk medicine. In this report, we have examined the inhibitory potency of protopanaxadiol ginsenosides (PPDGs) such as Rb1, Rb2 and Rc, and their co-treatment effect with known tumor necrosis factor (TNF)-alpha antagonists on TNF-alpha production in either murine (RAW264.7) or human (U937) macrophages stimulated with lipopolysaccharide (LPS). Rb1, and Rb2 strongly suppressed TNF-alpha production in RAW264.7 cells with an IC50 of 56.5 and 27.5 microM, respectively, and in differentiated U937 cells with an IC50 of 51.3, and 26.8 microM, respectively. The inhibitory activity of Rb1 and Rb2 was significantly increased by pharmacological agents against protein kinase C, protein tyrosine kinase, and protein kinase A, and anti-rheumatoid arthritis drugs, such as chloroquine and steroid drugs. In contrast, only cyclic AMP phosphodiesterase (cAMP PDE) inhibitors among cAMP-elevating agents did not change the inhibitory potency of PPDGs. These data suggest that PPDGs may possess potential therapeutic efficacy against TNF-alpha mediated disease and the therapeutic potency of PPDGs may be enhanced when co-treated with various kinds of known TNF-alpha antagonists but not with cAMP PDE inhibitors.
Cho
J Y
JY
Department of Immunopharmacology, R & D Center, Daewoong Pharmaceutical Co, Sungnam, Korea. jae.cho@ucl.ac.uk
Yoo
E S
ES
Baik
K U
KU
Park
M H
MH
Han
B H
BH
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036145:Ginsenosides; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D005894:Panax; D010946:Plants, Medicinal; D012503:Saponins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D002352:Carrier Proteins; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012503:Saponins; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; C015482:protein kinase modulator; C044462:ginsenoside Rc; C048026:ginsenoside Rb2; D003995:Dibutyryl Cyclic GMP; C049864:ginsenoside Re; D002738:Chloroquine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C035054:ginsenoside Rg1