Synergistic effect of baicalein, wogonin and oroxylin A mixture: multistep inhibition of the NF- κB signalling pathway contributes to an anti-inflammatory effect of Scutellaria root flavonoids

AbstractScutellaria root, the root ofScutellaria baicalensis Georgi, is a crude drug used for inflammatory diseases. In our previous report, the combination of flavonoids contained in Scutellaria root have been found to inhibit PGE2 production more strongly than individual flavonoids. Here, to investigate the mechanism of the synergistic effect, we examined the effects of an equimolar mixture (F-mix) of baicalein (1), wogonin (2) and oroxylin A (3) on the production of PGE2 in LPS-treated J774.1 cells. Although1 and3 inhibited COX-2 activity, the F-mix showed no synergistic effect on COX-2 inhibition. Therefore, we investigated the steps leading to the activation of COX-2 protein. Compounds1–3 and F-mix inhibited the expression of COX-2 protein. However, only2 inhibited the expression of COX-2 mRNA among the flavonoids, and the F-mix showed no synergistic effect. Only1 inhibited NF- κB translocation into the nucleus, and the F-mix showed no synergistic effect. Although2 did not affect NF- κB translocation, it strongly inhibited NF-κB-dependent transcriptional activity, and the F-mix inhibited the activity slightly more than2. Compounds1–3 also inhibited NO production, and the F-mix showed a synergistic effect. However, the effects of each flavonoid on the expression of iNOS mRNA were not consistent with those on COX-2 mRNA. Because the flavonoids inhibit different steps in the production of PGE2 and NO, and their mixture did not show apparent synergistic effects in eac...
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research