7,7'-Dihydroxy bursehernin inhibits the expression of inducible nitric oxide synthase through NF-kappaB DNA binding suppression. |
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Authors: | Yuba Raj Pokharel Qing-He Liu Dipendra Kumar Aryal Yoon Gyoon Kim Eun-Rhan Woo Keon Wook Kang |
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Institution: | BK21 Project Team, Chosun University, Gwangju 501-759, South Korea. |
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Abstract: | This study isolated a lignan, 7,7'-dihydroxy bursehernin, from Geranium thunbergii and investigated whether or not the lignan affects the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in RAW264.7 macrophages stimulated with lipopolysaccharide (LPS). The gel shift analysis and luciferase reporter gene assays using the iNOS promoter and nuclear factor-kappaB (NF-kappaB) minimal promoter showed that a treatment with 7,7'-dihydroxy bursehernin reduced the reporter activities and binding of NF-kappaB to the NF-kappaB consensus sequence, while it had no effect on the nuclear translocation of p65 and the phosphorylation/degradation of I-kappaBalpha. It was reported that a few natural compounds directly suppressed the binding activity of the NF-kappaB components to DNA. The NF-kappaB binding activity was not reversed by the in vitro exposure of the nuclear extracts to 7,7'-dihydroxy bursehernin, which suggest that a metabolite(s) of 7,7'-dihydroxy bursehernin might target the binding of the NF-kappaB complex to the DNA binding domain region in the promoter region of the iNOS gene. After incubation of RAW264.7 cells with 7,7-dihydroxy bursehernin for 18h, the levels of parent compound were negligible; while a main metabolite, 4-4-(n-hydroxy-phenyl)-2,3-dimethyl-buta-1,3-dienyl]-benzene-1,2-diol was detected in cell lysates and culture medium. |
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