**4.2 Effects on angiogenesis**

Angiogenesis is the process of development of new blood vessels with the help of endothelial cells. Chemical mediators within the body (angiogenic and antiangiogenic factors) maintain the environment required for normal angiogenesis. Angiogenic factors include growth factors such as vascular endothelial growth


**Table 2.**

*Effect of anthocyanin treatment in disease conditions and the tested pathological markers.*

*Anthocyanins: Natural Sources and Traditional Therapeutic Uses DOI: http://dx.doi.org/10.5772/intechopen.86888*

factor (VEGF), angiopoietin and fibroblast growth factor. Antiangiogenic factors include factors such as thrombospondins. Disruption in the balance between these factors can lead to complications in disorders such as diabetes and cancer.

Reports published on evaluation of expression of VEGF reveal that colored berries due to their anthocyanin contents, reduce expression of VEGF and VEGF induced tube formation in *ex-vivo* models of human cell lines, under oxidative stress [64]. When high glucose concentrations were induced in human endothelial cells, anthocyanins from purple corn were found to inhibit expression of angiogenic factors [65].

## **4.3 Antitumor activity**

Angiogenesis play a very critical role in proliferation of cancer cells. Reports suggest that anthocyanins extracted from berries have antiangiogenic effects in various cancer cell lines. Blue berry, bilberry and black rice anthocyanins are reported to exhibit anti-invasive properties in breast cancer cells and in *in-vivo* animal models by reducing the expression of cyclooxygenase-2 gene [65]. Other mechanisms of action reported for anticancer effect of black rice include suppression of activation of mitogen-activated protein kinase (MEK), and decreased expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) [66]. A study of purple potato anthocyanins in CF-1 mice model reports the antitumor effect of its extracts in colon cancer by induction of cell-cycle arrest [66].

### **4.4 Antidiabetic effects**

Anthocyanins from Cornus fruits are reported to induce insulin secretion in *ex-vivo* rodent beta cells. Cornus fruits are used in Traditional Chinese Medicine as antidiabetic agents. It is reported that the property of inducing insulin secretion in anthocyanins may be due to the hydroxyl groups in their B-ring [67]. Anthocyanins reported to induce insulin secretion include delphinidin-3-glucoside and pelargonidin-3-galactoside. Seoritae extract is reported to inhibit diabetic nephropathy by suppressing renal lipid deposition [68]. Anthocyanins from Bilberries act as antihyperglycemic agents by stimulating the adenosine monophosphate-activated protein kinase (AMPK). Bilberry extracts are also reported to improve visual function in patients suffering from diabetic neuropathy and glaucoma [69].

### **4.5 Neuroprotection**

Neuroprotection is achieved by reduction in toxic effects and injuries caused to neurons due to oxidative reactions. Cyanidin glucosides are reported to inhibit DNA fragmentation and oxidative stress caused due to hydrogen peroxide formed *in-vivo* in human neuronal cells [70]. Tart cherry anthocyanins, when tested for neuroprotective activity in mice brain under oxidative stress inhibited generation of apoptosis-inducing factor [71]. Cyanidin-3-O-β-d-glucopyranoside and petunidin-3-glucoside isolated from mulberry and black soybeans, are reported to exhibit neuroprotective activity in *ex-vivo* models. They inhibit cerebral ischemia and cell death caused due to hydrogen peroxide induced oxidative stress [72, 73].
