Premium
The Major Metabolites of 5‐Hydroxy Nobiletin Inhibit Lipopolysaccharide‐induced Inflammation in Macrophages
Author(s) -
Xiao Hang,
Guo Shanshan,
Zheng Jinkai,
Wu Xian
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.823.16
Subject(s) - nobiletin , lipopolysaccharide , nitric oxide , chemistry , pharmacology , inflammation , toxicity , metabolite , nitric oxide synthase , macrophage , carcinogen , biochemistry , biology , immunology , in vitro , flavonoid , organic chemistry , antioxidant
Our previous studies have demonstrated anti‐carcinogenic effects of 5‐hydroxy nobiletin (5HN), a unique polymethoxyflavone isolated from citrus fruits. We have identified three major urinary metabolites of 5HN in the mice, i.e. 3′,4′,5‐trihydroxy nobiletin (M1), 3′,5‐dihydroxy nobiletin (M2), and 4′,5‐dihydroxy nobiletin (M3). Herein, we studied the anti‐inflammatory effects of 5HN and these metabolites in lipopolysaccharide (LPS)‐treated RAW264.7 macrophages. Cell viability assay indicated that 5HN, M1 and M2 at up to 10 μM did not have any toxicity on macrophages, while M3 did not show toxicity at up to 50 μM. Within these non‐toxic concentrations, 5HN and M2 showed marginal inhibitory effects on LPS‐induced nitric oxide (NO) production in macrophages, whereas M1 and M3 showed 76% and 99% inhibition, respectively. Consistent with these results, M1 and M3 showed a dose‐dependent inhibition on the protein levels of iNOS in LPS‐treated macrophages. Moreover, real time qRT‐PCR indicated that M1 and M3 dose‐dependently suppressed mRNA levels of iNOS. Our results further demonstrated that M1 and M3 also significantly suppressed LPS‐induced production of IL‐1, which was associated with decreased mRNA levels of IL‐1. In conclusion, the urinary metabolites of 5HN in mice, i.e. M1 and M3 showed much stronger anti‐inflammatory effects than 5HN in LPS‐treated macrophages.