Identification of cyanidin glycosides as constituents of freeze-dried black raspberries which inhibit anti-benzo[a]pyrene-7,8-diol-9,10-epoxide induced NFkappaB and AP-1 activity.
Dietary freeze-dried black raspberries inhibit tumor induction by N-nitrosomethylbenzylamine in the rat esophagus, but the constituents responsible for this chemopreventive activity have not been identified. We fractionated freeze-dried black raspberries and used mouse epidermal JB6 Cl 41 cells stably transfected with either a nuclear factor kappa B (NFkappaB)- or an activator protein 1 (AP-1)-luciferase reporter, and treated with racemic anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), to assess the inhibitory effects of the fractions. The ethanol and water extracts of the freeze-dried black raspberries had inhibitory activity and these extracts were fractionated by HPLC to give several bioactive fractions. Further HPLC analysis yielded multiple subfractions, some of which inhibited BPDE-induced NFkappaB activity. Major constituents of the most active subfractions were identified by their spectral properties and in comparison with standards as cyanidin-3-O-glucoside, cyanidin 3-O-(2(G)-xylosylrutinoside) and cyanidin 3-O-rutinoside. Analysis of freeze-dried black raspberries indicated that these three components comprised approximately 3.4% of the material by dry weight. Consistent with these results, standard cyanidin-3-O-glucoside and cyanidin chloride were also good inhibitors of BPDE-induced NFkappaB activity. The results of this study demonstrate that cyanidin glycosides of freeze-dried black raspberries are bioactive compounds which could account for at least some of the chemopreventive activity observed in animal models.
Hecht
Stephen S
SS
The Cancer Center, University of Minnesota Minneapolis, MN 55455, USA. hecht002@umn.edu
Huang
Chuanshu
C
Stoner
Gary D
GD
Li
Jingxia
J
Kenney
Patrick M J
PM
Sturla
Shana J
SJ
Carmella
Steven G
SG
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology*; D000818:Animals; D000872:Anthocyanins / Q000032:analysis*; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005612:Freeze Drying; D005638:Fruit / Q000737:chemistry; D005960:Glucosides / Q000032:analysis*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D027824:Rosaceae / Q000737:chemistry*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000872:Anthocyanins; D002273:Carcinogens; D005960:Glucosides; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; C462279:cyanidin-3-O-beta-glucopyranoside; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide