Robeena M. Aziz

Pharmacokinetics of anthocyanins and ellagic acid in healthy volunteers fed freeze-dried black raspberries daily for 7 days.

Eleven subjects completed a clinical trial to determine the safety/tolerability of freeze‐dried black raspberries (BRB) and to measure, in plasma and urine, specific anthocyanins‐cyanidin‐3‐glucoside, cyanidin‐3‐sambubioside, cyanidin‐3‐rutinoside, and cyanidin‐3‐xylosylrutinoside, as well as ellagic acid. Subjects were fed 45 g of freeze‐dried BRB daily for 7 days. Blood samples were collected predose on days 1 and 7 and at 10 time points postdose. Urine was collected for 12 hours predose on days 1 and 7 and at three 4‐hour intervals postdose. Maximum concentrations of anthocyanins and ellagic acid in plasma occurred at 1 to 2 hours, and maximum quantities in urine appeared from 0 to 4 hours. Overall, less than 1% of these compounds were absorbed and excreted in urine. None of the pharmacokinetic parameters changed significantly between days 1 and 7. In conclusion, 45 g of freeze‐dried BRB daily are well tolerated and result in quantifiable anthocyanins and ellagic acid in plasma and urine.

Black Raspberry Extracts Inhibit Benzo(a)Pyrene Diol-Epoxide–Induced Activator Protein 1 Activation and VEGF Transcription by Targeting the Phosphotidylinositol 3-Kinase/Akt Pathway

Previous studies have shown that freeze-dried black raspberry extract fractions inhibit benzo(a)pyrene [B(a)P]-induced transformation of Syrian hamster embryo cells and benzo(a)pyrene diol-epoxide [B(a)PDE]-induced activator protein-1 (AP-1) activity in mouse epidermal Cl 41 cells. The phosphotidylinositol 3-kinase (PI-3K)/Akt pathway is critical for B(a)PDE-induced AP-1 activation in mouse epidermal Cl 41 cells. In the present study, we determined the potential involvement of PI-3K and its downstream kinases on the inhibition of AP-1 activation by black raspberry fractions, RO-FOO3, RO-FOO4, RO-ME, and RO-DM. In addition, we investigated the effects of these fractions on the expression of the AP-1 target genes, vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). Pretreatment of Cl 41 cells with fractions RO-F003 and RO-ME reduced activation of AP-1 and the expression of VEGF, but not iNOS. In contrast, fractions RO-F004 and RO-DM had no effect on AP-1 activation or the expression of either VEGF or iNOS. Consistent with inhibition of AP-1 activation, the RO-ME fraction markedly inhibited activation of PI-3K, Akt, and p70 S6 kinase (p70(S6k)). In addition, overexpression of the dominant negative PI-3K mutant delta p85 reduced the induction of VEGF by B(a)PDE. It is likely that the inhibitory effects of fractions RO-FOO3 and RO-ME on B(a)PDE-induced AP-1 activation and VEGF expression are mediated by inhibition of the PI-3K/Akt pathway. In view of the important roles of AP-1 and VEGF in tumor development, one mechanism for the chemopreventive activity of black raspberries may be inhibition of the PI-3K/Akt/AP-1/VEGF pathway.

Prevention and therapy of squamous cell carcinoma of the rodent esophagus using freeze-dried black raspberries

AbstractAim:This study was conducted to determine if short-term treatment of N-nitrosomethylbenzylamine (NMBA)-induced tumors in the rat esophagus with dietary freeze-dried black raspberries (FBR) would result in tumor regression and enhanced survival of the animals.Methods:Four-week-old male Fisher-344 rats were administered an AIN-76A control diet and injected subcutaneously with 0.5 mg/kg NMBA once per week for 15 weeks. At 19 weeks, when rats had an average of 5–6 tumors (papillomas) per esophagus, they were given a control diet containing either 5%, 10%, or 20% FBR. After 7 weeks of berry treatment, all surviving rats were killed and tumor incidence, number and volume were determined.Results:Esophageal tumor incidences, numbers and volumes in NMBA-treated rats were not influenced by any of the berry treatments. There were progressive increases in the survival of NMBA-treated rats fed 5%–20% FBR diets; however, these increases were not significant.Conclusion:FBR at 5%, 10%, and 20% of the diet had no effect on the development of NMBA-induced tumors in the rat esophagus or on animal survival when administered for 7 weeks beginning at the papilloma stage of tumor development. Thus, FBR appear to have no therapeutic value in the treatment of esophageal tumors. In contrast, dietary FBR are highly effective in preventing the development of NMBA-induced esophageal tumors in rats when administered before and during NMBA treatment or shortly after NMBA treatment when the esophagi contain preneoplastic (dysplastic) lesions of varying degrees of severity.