Flavonoids, centaurein and centaureidin, from Bidens pilosa, stimulate IFN-γ expression

Bidens pilosa is used as an ethnical medicine for bacterial infection or immune modulation in Asia, America and Africa. Here, we employed an IFN-gamma promoter-driven luciferase reporter construct and T cells to characterize immunomodulatory compounds from this plant based on a bioactivity-guided isolation principle. We found that PHA, a positive control, caused a six-fold increase in IFN-gamma promoter activity. In contrast, hot water crude extracts from Bidens pilosa and its butanol subfraction increased IFN-gamma promoter activity to two- and six-fold, respectively. Finally, centaurein (EC50 = 75 mu g/ml) and its aglycone, centaureidin (EC50 = 0.9 mu g/ml), isolated from this butanol subtraction, augmented IFN-gamma promoter activity by similar to four-fold. Consistent with the role of centaurein or its aglycone in IFN-gamma regulation, we showed that centaurein induced the activity of NEAT and NF kappa B enhancers, located within the IFN-gamma promoter, in Jurkat cells. Overall, our results showed that centaurein regulated IFN-gamma transcription, probably via NFAT and NF kappa B in T cells. (c) 2007 Elsevier Ireland Ltd. All rights reserved.