7,7'-Dihydroxy bursehernin inhibits the expression of inducible nitric oxide synthase through NF-kappaB DNA binding suppression.
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.
Pokharel
Yuba Raj
YR
BK21 Project Team, Chosun University, Gwangju 501-759, South Korea.
Liu
Qing-He
QH
Aryal
Dipendra Kumar
DK
Kim
Yoon Gyoon
YG
Woo
Eun-Rhan
ER
Kang
Keon Wook
KW
D000818:Animals; D001483:Base Sequence; D001593:Benzyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism
C518689:7,7'dihydroxybursehernin; D001593:Benzyl Compounds; D017931:DNA Primers; D004791:Enzyme Inhibitors; D007783:Lactones; D017705:Lignans; D016328:NF-kappa B; D004247:DNA; D052247:Nitric Oxide Synthase Type II