- Hidehiko Kikuchi (Department of Food and Nutrition, Shokei University Junior College / firstname.lastname@example.org)
1) Department of Food and Nutrition, Shokei University Junior College , 2) Department of Applied Physiology, Faculty of Medicine, University of Miyazaki , 3) Department of Biochemistry, Kawasaki Medical School
Flavones are belonging to flavonoids group and show diverse biological functions. Therefore, they have much attention as drugs for maintaining human health via contributing prevention and treatment of various diseases like cancers, diabetes, neurodegenerative diseases, ischemic stroke, inflammation diseases and cardiovascular diseases. On the other hand, human monoblastic leukemia U937 cells have been used as an excellent in vitro model system for macrophage development induced in response to various reagents such as all-trans retinoic acid (RA). Here, we investigated the effects of flavones (flavone and its hydroxy derivatives) on the RA-induced O2--generating activity of U937 cells. Very interestingly, at a concentration of 20 μM, 3’, 4’-dihydroxyflavone caused up-regulation of the RA-induced O2--generating activity (to ~ 170%) although flavone and other hydroxyflavone derivatives tested showed remarkable inhibitory effects on the RA-induced O2--generating activity. The promoting effects of 3’, 4’-dihydroxyflavone on the RA-induced O2--generating activity showed the maximum value at a concentration of 10 μM. Semiquantitative RT-PCR and immunoblotting revealed that 10 μM 3’, 4’-dihydroxyflavone up-regulates the RA-induced O2--generating activity via enhancing gene expression of gp91-phox (mRNA level: to ~ 160%, protein level: to ~ 200%) while 10 μM 5, 7-dihydroxyflavone and 10 μM 3’, 4’, 5, 7-tetrahydroxyflavone down-regulate the RA-induced O2--generating activity via inhibiting gene expression of gp91-phox and p47-phox. These findings also showed that there may be various risks involved in use of phytochemical mixtures.