Inhibitory Mechanism of 10-Hydroxy- trans -2-decenoic Acid (Royal Jelly Acid) Against Lipopolysaccharide- and Interferon
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Inhibitory Mechanism of 10-Hydroxy-trans-2-decenoic Acid (Royal Jelly Acid) Against Lipopolysaccharide- and Interferonβ-Induced Nitric Oxide Production Tsuyoshi Sugiyama,1,2 Keita Takahashi,1 Akihiro Kuzumaki,1 Shunji Tokoro,1 Paola Neri,1 and Hiroshi Mori1
Abstract—Royal jelly acid, 10-hydroxy-trans-2-decenoic acid (10H2DA), is a major lipid component of royal jelly, which is the exclusive diet of queen honeybees. Previously, we showed partial inhibition of lipopolysaccharide (LPS)-induced NF-κB activation by 10H2DA. In this study, the ability of 10H2DA to inhibit LPS-induced nitric oxide (NO) production was investigated. LPSinduced NO production and inducible NO synthase (iNOS) gene transcription were inhibited by 10H2DA. LPS-stimulated interferon (IFN)-β production, IFN regulatory factor-1 induction and IFN-stimulated response element activation, which are required for iNOS induction, were unaffected by 10H2DA. IFN-β-induced NO production, however, was significantly inhibited by 10H2DA. Furthermore, IFN-β-induced nuclear factor (NF)-κB activation and tumour necrosis factor (TNF)-α production were significantly inhibited by 10H2DA, and TNF-α-induced NF-κB activation was also inhibited by 10H2DA. These results and our previous study suggest that 10H2DA inhibits LPS- and IFN-β-induced NO production via inhibition of NF-κB activation induced by LPS or IFN-β. KEY WORDS: fatty acid; lipopolysaccharide; nitric oxide; royal jelly.
[6]. 10H2DA is responsible for some of the pharmacological activities of royal jelly, including its anti-tumour and anti-bacterial activities [7–9]. We previously showed that 10H2DA exerted an inhibitory effect on lipopolysaccharide (LPS) and interferon (IFN)-γ signaling [10, 11]. Among the cytokines and chemokines upregulated by LPS stimulation, only interleukin (IL)-6 was inhibited by 10H2DA, by a mechanism involving specific inhibition of inhibitor of nuclear factor (NF)-κB (IκB)-ζ gene expression. In the case of IFN-γ-stimulation, 10H2DA inhibited nitric oxide (NO) production through inhibition of IFN regulatory factor (IRF)-8 induction, followed by reduction of tumour necrosis factor (TNF)-α production, which is an essential step in IFN-γ-induced NO production [12]. LPS is also known to induce NO production in murine macrophages. The promoter region of inducible NO synthase (iNOS), which is responsible for much of the NO production in macrophages, contains κB and IFN-stimulated response element (ISRE) sequences, which bind the transcription factors NF-κB and IFN-stimulated gene factor 3, respectively
INTRODUCTION Royal jelly is produced by honeybees and is widely used as a dietary supplement. Nurse bees secrete royal jelly from the hypopharyngeal and mandibular glands [1] and feed it to all larvae for 3 days, but to queen bee larvae throughout their lives [2]. Royal jelly has been reported to have many pharmacological activities, including anti-inflammatory, anti-tumour and anti-bacterial activities [3–5]. It contains 10-hydroxy-trans-2decenoic acid (10H2DA), which is a major and unique lipi
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