Inhibition of Prostaglandin E2 Production by a Combination of Flavonoids from Scutellaria baicalensis

Crude drugs are used in many traditional medicines all over the world, and WHO emphasized their role in primary health care. In Japan, traditional Kampo medicine is used along with modern medicine [1] and the use of Kampo formulae is increasing. Kampo medicine has a long history of use in Japan. However, the scientific basis of the effectiveness of Kampo formulae is still not suffiucient. In a previous paper [2], we analysed the anti-inflammatory effect of Orengedokuto, a Kampo formula used for inflammatory diseases, using inhibition of prostaglandin (PG) E2 production in lipopolysaccharide (LPS) stimulated J774.1 cells, and showed that a mixture of flavonoids from Scutellaria Root (the root of Scutellaria baicalensis), one of the four constituent crude drugs of the formula, played an important role in the activity. A mixture of baicalein, wogonin, oroxylin A and 6-methoxywogonin inhibited production of PG E2 more potently than any of the individual flavonoid [2]. In this work, we examined the mechanisms of action of three of the flavonoids, i.e. baicalein, wogonin and oroxylin A. Oroxyln A and baicalein directly inhibited COX-2, whereas no synergistic effect was observed for a mixture of the flavonoids. Baicalein inhibited translocation of NF-κB into the nucleus, whereas wogonin most potently inhibited NF-κB initiated transcription, and a synergistic effect of the mixture was obserbed. Expression of the COX-2 protein was inhibited by all of the flavonoids. Thus, although the flavonoids have similar structures, the mechanisms of action of each flavonoid are different, and by inhibiting different steps of the LPS induced PG E2 production, they showed a synergistic effect.