Flavonoids, centaurein and centaureidin, from Bidens pilosa, stimulate IFN-gamma 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 (EC(50)=75 microg/ml) and its aglycone, centaureidin (EC(50)=0.9 microg/ml), isolated from this butanol subfraction, augmented IFN-gamma promoter activity by approximately four-fold. Consistent with the role of centaurein or its aglycone in IFN-gamma regulation, we showed that centaurein induced the activity of NFAT and NFkappaB enhancers, located within the IFN-gamma promoter, in Jurkat cells. Overall, our results showed that centaurein regulated IFN-gamma transcription, probably via NFAT and NFkappaB in T cells.
Chang
Shu-Lin
SL
Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan.
Chiang
Yi-Ming
YM
Chang
Cicero Lee-Tian
CL
Yeh
Hsu-Hua
HH
Shyur
Lie-Fen
LF
Kuo
Yueh-Hsiung
YH
Wu
Tung-Kung
TK
Yang
Wen-Chin
WC
D031176:Bidens / Q000737:chemistry*; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007369:Interferon Inducers; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D019169:Jurkat Cells; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D005419:Flavonoids; D005960:Glucosides; D007369:Interferon Inducers; D016328:NF-kappa B; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; C111521:centaurein; C083161:centaureidin; D007371:Interferon-gamma; C022616:thiazolyl blue