Gigantol Isolated from the Whole Plants of Cymbidium goeringii Inhibits the LPS-Induced iNOS and COX-2 Expression via NF-κB Inactivation in RAW 264.7 Macrophages Cells

Abstract

During our efforts to find bioactive natural products with anti-inflammatory activity, we isolated gigantol from the whole plants of Cymbidium goeringii (Orchidaceae) by activity-guided chromatographic fractionation. Gigantol was found to have potent inhibitory effects on LPS-induced nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in RAW 264.7 cells. Consistent with these findings, gigantol suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in RAW 264.7 cells in a concentration-dependent manner. Our data also indicate that gigantol is a potent inhibitor of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) release and influenced the mRNA expression levels of these cytokines in a dose-dependent manner. Furthermore, a reporter gene assay for nuclear factor kappa B (NF-κB) and an electromobility shift assay (EMSA) demonstrated that gigantol effectively inhibited the activation of NF-κB, which is necessary for the expression of iNOS, COX-2, TNF-α, IL-1β and IL-6. Thus, our studies suggest that gigantol inhibits LPS-induced iNOS and COX-2 expression by blocking NF-κB activation.

Key words

Cymbidium goeringii - Orchidaceae - gigantol - inducible nitric oxide synthase - cyclooxygenase-2 - NF-κB

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