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

D. Bagchi^1*, C. K. Sen², M. Bagchi¹, and M. Atalay³

¹Department of Pharmacy Sciences, Creighton University Medical Center, 2500 California Plaza, Omaha, NE 68178, USA; fax: 402-280-1883; E-mail: debsis@creighton.edu

²Laboratory of Molecular Medicine, Department of Surgery, 512 Davis Heart and Lung Research Institute, The Ohio State University Medical Center, 473 W. 12th Avenue, Columbus, OH 43210, USA; fax: 614-247-7818; E-mail: sen-1@medctr.osu.edu

³Department of Physiology, University of Kuopio, P.O. Box 1627, FIN-70211, Kuopio, Finland; fax: +358-17-163-112; E-mail: Mustafa.atalay@uku.fi

^* To whom correspondence should be addressed.

Received April 30, 2003

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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-alpha-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 an in vivo model of angiogenesis, OptiBerry significantly inhibited basal MCP-1 and inducible NF-kappaB 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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KEY WORDS: berry anthocyanins, antioxidants, angiogenesis, keratinocytes, hemangioma

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