Suppression by a sesquiterpene lactone from Carpesium divaricatum of inducible nitric oxide synthase by inhibiting nuclear factor-κB activation
2001; Elsevier BV; Volume: 61; Issue: 7 Linguagem: Inglês
10.1016/s0006-2952(01)00538-x
ISSN1873-2968
AutoresEun Ju Kim, Hye Kyoung Jin, Yong Kee Kim, Hoi Young Lee, Seok‐Yong Lee, Kang Ro Lee, Ok Pyo Zee, Jeung Whan Han, Hyang Woo Lee,
Tópico(s)Phytochemistry and Biological Activities
ResumoExcessive nitric oxide (NO) produced by inducible NO synthase (iNOS) acts as a causative regulator in various inflammatory disease states. Carpesium divaricatum has been used in Korean traditional herbal medicine for its antipyretic, analgesic, vermifugic, and anti-inflammatory properties. We investigated the molecular mechanism for the suppression of lipopolysaccharide/interferon-γ (LPS/IFN-γ)-induced NO production in RAW 264.7 macrophages by the sesquiterpene lactone 2β,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-isobutyloxy-germacran-8α,12-olide (C-1), which has been identified recently as a new compound from C. divaricatum. C-1 decreased NO production in LPS/IFN-γ-stimulated RAW 264.7 cells in a concentration-dependent manner, with an ic50 of approximately 2.16 μM; however, it had no direct effect on the iNOS activity of fully LPS/IFN-γ-stimulated RAW 264.7 cells. Furthermore, treatment with C-1 led to a decrease in iNOS protein and mRNA. These effects appear to be due to inhibition of nuclear factor-κB (NF-κB) activation through a mechanism involving stabilization of the NF-κB/inhibitor of the κB (I-κB) complex, since inhibition of NF-κB DNA binding activity by C-1 was accompanied by a parallel reduction of nuclear translocation of subunit p65 of NF-κB and I-κBα degradation. Taken together, the results suggest that the ability of C-1 to inhibit iNOS gene expression may be responsible, in part, for its anti-inflammatory effects.
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