title: Inhibitory Aromatase Effects of Flavonoids from Ginkgo Biloba Extracts on Estrogen Biosynthesis.
abstract: Ginkgo biloba extract (GBE) is a popular phytomedicine and has been used for disorders of the central nervous system, cardiovascular, renal, respiratory, and circulatory diseases. Although GBE is a complex mixture of over 300 compounds, its major components are 24% flavonoids and 6% terpene lactones. In this study, we tested the inhibitory effects of the three major flavonoids (kaempferol, quercetin, and isorhamnetin) from GBE, independently and as mixtures, on aromatase activity using JEG-3 cells (human placental cells) and recombinant proteins (human placental microsome). In both systems, kaempferol showed the strongest inhibitory effects among the three flavonoids; the flavanoid mixtures exerted increased inhibitory effects. The results of exon I.1-driven luciferase reporter gene assays supported the increased inhibitory effects of flavonoid mixtures, accompanied by suppression of estrogen biosynthesis. In the RT-PCR analysis, decreased patterns of aromatase promoter I.1 mRNA expressions were observed, which were similar to the aromatase inhibition patterns of flavonoids and their mixtures. The present study demonstrated that three flavonoids synergistically inhibit estrogen biosynthesis through aromatase inhibition, decrease CYP19 mRNA, and induce transcriptional suppression. Our results support the usefulness of flavonoids in adjuvant therapy for breast cancer by reducing estrogen levels with reduced adverse effects due to estrogen depletion.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, Korea E-mail : ohsm0403@hoseo.edu, khchung@skku.edu.
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Park
authors.forename: Wun Hak
authors.initials: WH
authors.lastname: Choo
authors.forename: Ha Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Kyu Hyuck
authors.initials: KH
authors.lastname: Chung
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Oh
mesh_terms: D001141:Aromatase / Q000187:drug effects* / Q000235:genetics; D047072:Aromatase Inhibitors / Q000494:pharmacology; D053898:Biosynthetic Pathways / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D020441:Ginkgo biloba; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology; D010920:Placenta / Q000166:cytology; D010936:Plant Extracts / Q000494:pharmacology*; D011247:Pregnancy; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D005419:Flavonoids; D044949:Kaempferols; D010936:Plant Extracts; D012333:RNA, Messenger; D011994:Recombinant Proteins; C047368:3-methylquercetin; C006552:kaempferol; D011794:Quercetin; D001141:Aromatase