**3. Anthocyanins' potential health benefits**

rich anthocyanins fruits and vegetables. In their natural environments, plants are vulnerable because of multiple attacks by many different species of herbivores and also pathogens [5]. A vast spectrum of secondary metabolites have been demonstrated to act against their predators [6]. Among them are the phenolics, a large group of structurally diverse compounds, as well as certain flavonoids such as the anthocyanins. There are several ways anthocyanins assist plants in their defense against other organisms, such as chemical repellents and visual signals [7]. Along with other flavonoids, certain anthocyanins have demonstrable antiviral, antibacterial, and fungicidal activities. Also, it is generally accepted that the colors of flowers and fruits enhance reproductive success by facilitating communication between plants, their pollinators, and seed-dispersers [8]. Another positive propriety of anthocyanins is that they have demonstrated to exhibit antioxidant potential *in vitro* and *in vivo*. The antioxidant potential of anthocyanins have been demonstrated *in vitro* using several cell culture lines including ovarian, colon, endothelial liver, breast, leukemic cells, and keratinocytes [9–17]. Applied *in vitro* as treatment, anthocyanins have exhibited multiple antiproliferative and anticarcinogenic effects [18, 19]. The antioxidant activity of anthocyanins is a great property and was demonstrated that their chemical structure seems to be

Anthocyanins occur naturally in fruits and vegetables as glycosides, having one or more sugar attached to an aglycone nucleus (anthocyanidin). Their aglycones share a C6-C3-C6 carbon skeleton, characterized by the presence of two benzyl rings (A and B) and a heterocy-

responsible for that [20–23].

clic ring (C) [24].

**2. Chemical structure of anthocyanins**

76 Phytochemicals - Source of Antioxidants and Role in Disease Prevention

**Figure 1.** Chemical structure of the six most common anthocyanidins.

Since we consume a great amount of fruits, the daily intake of anthocyanins is highly variable and dependent on eating habits. Residents of the United States consume about 12.5 mg/day while in Europe, a highest consumption was found in Italy, about 64.9 mg/day [29, 30]. Many studies have suggested that anthocyanins have antioxidant, anti-inflammatory, and anticarcinogenic properties and lower the risk of cardiovascular disease, diabetes, arthritis, and cancer due, at least in part, to their antioxidant and anti-inflammatory activities (**Figure 2**) [19, 26, 31, 32].

**Figure 2.** Anticancer properties of anthocyanins.

Reactive oxygen species (ROS) are produced by all aerobic cells and are important to the immune system, cell signaling, and many other normal body functions. They can elicit cellular damage, leading to degenerative diseases such as inflammation, cardiovascular disease, cancer, and aging if ROS are excessively produced [33–35]. As we mention previously, anthocyanins are potent antioxidants and their effectiveness has been tested *in vitro* and *in vivo*. They quench free radicals and terminate the chain reaction that is responsible for the oxidative damage. Because of the pH in the human body, their antioxidant activity at a neutral pH has a particular importance [36]. To assess the *in vivo* antioxidant activity of anthocyanins, an anthocyanin mixture was administered to mice/rats that were subjected to psychological stress [37, 38]. It was noticed that anthocyanins have similar antioxidant potency as vitamin E (α-tocopherol). Dietary anthocyanins have the potential to increase serum antioxidant capacity and thereby protect against LDL oxidation and prevent cardiovascular diseases as demonstrated in a human trial [39]. Deposits oxidized cholesterol into the artery wall can lead to atherosclerosis and eventually cardiovascular diseases [40]. Several studies have shown that anthocyanins have anti-obesity effect on high-fat diets and consequently may contribute to the prevention of type 2 diabetes. One of the studies demonstrates that black soybean anthocyanins were found to effectively reverse the weight gain of high-fat diet group rats [41]. Moreover, a number of different reports indicate that consumption of fruits and vegetables, especially rich in polyphenols, decrease the incidence of type-2 diabetes, a condition associated with insulin resistance [42, 43]. Nevertheless, evidence in the use of anthocyanins to improve night vision was also revealed in other scientific articles [44, 45].

the programed cell death, in tumor cells is not present; therefore, dead cells cannot be eliminated normally. Cancer cells have deregulated several genes to avoid the apoptosis, such as p53, and these cells have high resistance to death compared with normal cells. In the intrinsic pathway, cytochrome *c* release and modulation of caspase-dependent anti- and proapoptotic proteins appear as an increase in mitochondrial membrane potential, because of anthocyanin treatment on cancer cells. In the extrinsic pathway, the expression of FAS and FASL is modulated by anthocyanins resulting apoptosis in cancer cells [50–52]. Lately, anthocyanins have been shown to suppress angiogenesis through several mechanisms such as: inhibition

Anthocyanins-Smart Molecules for Cancer Prevention http://dx.doi.org/10.5772/intechopen.79613 79

and tumor necrosis factor alpha (TNF-α)-induced VEGF expression in epidermal

keratinocytes and by reducing VEGF and VEGF receptor expression in endothelial cells [53]. Angiogenesis is the physiological process of forming new blood vessels from the existing vascular network for the growth and metastasis of malignant tumors. The process of angiogenesis is controlled by multiple cytokines, of which the most important factor is vascular endothelial growth factor (VEGF); therefore, inhibiting the receptor of angiogenesis vascular endothelial growth factor receptor (VEGFR) could inhibit the metastasis of tumors effectively [18]. Anthocyanins were found to inhibit cancer cell invasion by reducing the expression of matrix metalloproteinase (MMP) and urokinase plasminogen activator (u-PA), both of which degrade extracellular matrix as part of the invasive process and, by stimulating the expression of inhibitors, both of which counteract the action of MMP and uPA [54]. There are two main aspects of cancer cells that threaten patient's health and life: invasion and metastasis. Successful tumor cell extravasation is successful by facilitating degradation of the extracellular matrix barriers. The balance of activated proteases and their naturally occurring inhibitors

In carcinogen-treated animals and also animals with a hereditary predisposition to cancer, anthocyanins have been shown to inhibit the development of cancer. Moreover, they have been proven effective in: esophageal cancer, colon cancer, skin cancer, and lung cancer. After treatment, administration in different forms, such as anthocyanin-rich tart cherry extract,

certain effects, were observed. All diets were equally effective in preventing the development of tumors, reducing tumor numbers by 42–47%, suggesting that anthocyanins in the fruits are important for their chemopreventive activity. A small summary of several types of cancer will

Colon cancer is one of the most prevalent diseases across the world. In the United States, colon cancer is the second most prevalent cause of death from cancer in men and women after lung cancer, with approximately 50,310 causes of death [56]. In Europe, colorectal cancer is the second most common cancer, with 50,000 new cases diagnosed in 2012 [57]. The development of colon cancer is associated with high alcohol consumption, high-fat diet poor in fiber, red

O extract from berries,

determine the degradation of the basement membrane [55].

black raspberry powder, lyophilized black raspberries or ethanol: H<sup>2</sup>

of H2 O2

**5.** *In vivo* **studies**

be discussed further.

**5.1. Colon cancer**
