Anti-angiogenic, Antioxidant, and Anti-carcinogenic Properties of a Novel Anthocyanin-Rich Berry Extract Formula


Edible berry anthocyanins possess a broad spectrum of therapeutic and anti-carcinogenic properties. Berries are rich in anthocyanins, compounds that provide pigmentation to fruits and serve as natural antioxidants. Anthocyanins repair and protect genomic DNA integrity. Earlier studies have shown that berry anthocyanins are beneficial in reducing age-associated oxidative stress, as well as in improving neuronal and cognitive brain function. Six berry extracts (wild blueberry, bilberry, cranberry, elderberry, raspberry seeds, and strawberry) were studied for antioxidant efficacy, cytotoxic potential, cellular uptake, and anti-angiogenic (the ability to reduce unwanted growth of blood vessels, which can lead to varicose veins and tumor formation) properties. We evaluated various combinations of edible berry extracts and developed a synergistic formula, OptiBerry IH141, which exhibited high ORAC (Oxygen-Radical Absorbing Capacity) value, low cytotoxicity, and superior anti-angiogenic properties compared to the other combinations tested. Anti-angiogenic approaches to treat cancer represent a priority area in vascular tumor biology. OptiBerry significantly inhibited both H2O2- and TNF-α-induced VEGF (Vascular Endothelial Growth Factor) expression by human keratinocytes. VEGF is a key regulator of tumor angiogenesis. Matrigel assay using human microvascular endothelial cells showed that OptiBerry impaired angiogenesis. In anin vivo model of angiogenesis, OptiBerry significantly inhibited basal MCP-1 and inducible NF-κB transcriptions. Endothelioma cells pretreated with OptiBerry showed a diminished ability to form hemangioma and markedly decreased tumor growth by more than 50%. In essence, these studies highlight the novel anti-angiogenic, antioxidant, and anti-carcinogenic potential of a novel anthocyanin-rich berry extract formula, OptiBerry.

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  1. 1.

    Francis, E. L. (1989)Crit. Rev. Food Sci. Nutr.,28, 273–314.

    Google Scholar 

  2. 2.

    Roy, S., Khanna, S., Alessio, H. M., Vider, J., Bagchi, D., Bagchi, M., and Sen, C. K. (2002)Free Rad. Res.,36, 1023–1031.

    Google Scholar 

  3. 3.

    Xue, H., Aziz, R. M., Sun, N., Cassady, J. M., Kamendulis, L. M., Xu, Y., Stoner, G. D., and Klaunig, J. E. (2001)Carcinogenesis,22, 831–833.

    Google Scholar 

  4. 4.

    McCarty, M. F. (2001)Med. Hypotheses,56, 137–154.

    Google Scholar 

  5. 5.

    Kresty, L. A., Morse, M. A., Morgan, C., Carlton, P. S., Lu, J., Gupta, A., Blackwood, M., and Stoner, G. D. (2001)Cancer Res.,61, 6112–6119.

    Google Scholar 

  6. 6.

    Ofek, I., Goldhar, J., Zafriri, D., Lis, H., Adar, R., and Sharon, N. (1991)N. Engl. J. Med.,324, 1599.

    Google Scholar 

  7. 7.

    Willett, W. C. (1995)Environ. Health Perspect.,103, 165–170.

    Google Scholar 

  8. 8.

    Harborne, J. B., and Williams, C. A. (2001)Nat. Prod. Rep.,18, 310–333.

    Google Scholar 

  9. 9.

    Aruoma, O. I. (1994)Food Chem. Toxicol.,32, 671–683.

    Google Scholar 

  10. 10.

    Bagchi, D., Garg, A., Krohns, R. L., Bagchi, M., Tran, M. X., and Stohs, S. J. (1997)Res. Commun. Mol. Pathol. Pharmacol.,95, 179–189.

    Google Scholar 

  11. 11.

    Tapiero, H., Tew, K. D., Ba, G. N., and Mathe, G. (2002)Biomed. Pharmacother.,56, 200–207.

    Google Scholar 

  12. 12.

    Harborne, J. B., and Williams, C. A. (2000)Phytochemistry,55, 481–504.

    Google Scholar 

  13. 13.

    Amouretti, M. (1972)Therapeutique,48, 579–581.

    Google Scholar 

  14. 14.

    Bettini, V., Fiori, A., Martino, R., Mayellaro, F., and Ton, P. (1985)Fitoterapia,56, 67–72.

    Google Scholar 

  15. 15.

    Narayan, M. S., Naidu, K. A., Ravishankar, G. A., Srinivas, L., and Venkataraman, L. V. (1999)Prostaglandins, Leukot. Essent. Fatty Acids,60, 1–4.

    Google Scholar 

  16. 16.

    Camire, M. E. (2000) inHerbs, Botanicals Teas (Mazza, G., and Oomah, B. D., eds.) Lancaster, PA, pp. 289–319.

  17. 17.

    Cao, G., Russell, R. M., Lischner, N., and Prior, R. L. (1998)J. Nutr.,128, 2383–2390.

    Google Scholar 

  18. 18.

    Waterhouse, A. L. (2002)Ann. N. Y. Acad. Sci.,957, 21–36.

    Google Scholar 

  19. 19.

    Brouillard, R., George, F., and Fougerousse, A. (1997)Biofactors,6, 403–410.

    Google Scholar 

  20. 20.

    Yasmin, T., Sen, C. K., Hazra, S., Bagchi, M., Bagchi, D., and Stohs, S. J. (2003)Res. Commun. Pharmacol. Toxicol., in press.

  21. 21.

    Cao, G., Alessio, H. M., and Cutler, R. G. (1993)Free Rad. Biol. Med.,14, 303–311.

    Google Scholar 

  22. 22.

    Bagchi, D., Bagchi, M., Stohs, S. J., Das, D. K., Ray, S. D., Kuszynski, C. A., Joshi, S. S., and Preuss, H. G. (2000)Toxicology,148, 187–197.

    Google Scholar 

  23. 23.

    Giavazzi, R., and Taraboletti, G. (1999)Forum,9, 261–272.

    Google Scholar 

  24. 24.

    Griffioen, A. W., and Molema, G. (2000)Pharmacol. Rev.,52, 237–268.

    Google Scholar 

  25. 25.

    Detmar, D. (2000)J. Dermatol. Sci.,24, S78–S84.

    Google Scholar 

  26. 26.

    Ponce, M. L., Nomizu, M., and Kleinman, H. K. (2001)FASEB J.,15, 1389–1397.

    Google Scholar 

  27. 27.

    Folkman, J., Mulliken, J., and Ezekowitz, R. (1997) inSurgery of Infants and Children: Scientific Principles and Practices (Oldham, K., ed.) Lippincott-Raven, PA, pp. 569–584.

  28. 28.

    Boye, E., Yu, Y., Paranya, G., Mulliken, J., Olsen, B., and Bischoff, J. (2001)J. Clin. Invest.,107, 745–752.

    Google Scholar 

  29. 29.

    Salcedo, R., Ponce, M. L., Young, H. A., Wasserman, K., Ward, J. M., Kleinman, H. K., Oppenheim, J. J., and Murphy, W. J. (2000)Blood,96, 34–40.

    Google Scholar 

  30. 30.

    Atalay, M., Gordillo, G., Roy, S., Rovin, B., Bagchi, D., Bagchi, M., and Sen, C. K. (2003)FEBS Lett.,544, 252–257.

    Google Scholar 

  31. 31.

    Paper, D. H. (1998)Planta Med.,64, 686–695.

    Google Scholar 

  32. 32.

    Jiang, C., Agarwal, R., and Lu, J. (2000)Biochem. Biophys. Res. Commun.,276, 371–378.

    Google Scholar 

  33. 33.

    Fotsis, T., Pepper, M. S., Aktas, E., Breit, S., Rasku, S., Adlercreutz, H., Wahala, K., Montesano, R., and Schweigerer, L. (1997)Cancer Res.,57, 2916–2921.

    Google Scholar 

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Bagchi, D., Sen, C.K., Bagchi, M. et al. Anti-angiogenic, Antioxidant, and Anti-carcinogenic Properties of a Novel Anthocyanin-Rich Berry Extract Formula. Biochemistry (Moscow) 69, 75–80 (2004).

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  • berry anthocyanins
  • antioxidants
  • angiogenesis
  • keratinocytes
  • hemangioma