In Vitro Inhibitory Effect of Protopanaxadiol Ginsenosides on Tumor Necrosis Factor (TNF)-α Production and its Modulation by Known TNF-α Antagonists

Abstract

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)-α antagonists on TNF-α production in either murine (RAW264.7) or human (U937) macrophages stimulated with lipopolysaccharide (LPS). Rb₁, and Rb₂ strongly suppressed TNF-α production in RAW264.7 cells with an IC₅₀ of 56.5 and 27.5 μM, respectively, and in differentiated U937 cells with an IC₅₀ of 51.3, and 26.8 μM, 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-α mediated disease and the therapeutic potency of PPDGs may be enhanced when co-treated with various kinds of known TNF-α antagonists but not with cAMP PDE inhibitors.

Panax ginseng - Araliaceae - protopanaxadiol ginsenosides - tumor necrosis factor-α production, drug interaction

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