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Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects

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Polyphenols: Extraction Methods, Antioxidative Action, Bioavailability and Anticarcinogenic Effects ( polyphenols-extraction-methods-antioxidative-action-bioavail )

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Molecules 2016, 21, 901 2 of 38 occurring dietary polyphenols are flavonoids and phenolic acids [6]. In plants, polyphenols are generally involved in defense against different types of stress [7]. They offer protection against reactive oxygen and nitrogen species, UV light, pathogens, parasites and plant predators. Additionally, they contribute substantially to the organoleptic properties of plants, food and cosmetics [8]. Ancient civilizations have exploited their numerous biological effects for promotion and improvement of health for centuries [9]. In contrast, our knowledge of their properties has been until recently very limited [8]. Not so long ago polyphenols were even treated as non-essential anti-nutrients [10]. Nowadays ample evidence from copious studies exists of their antioxidative, anti-inflammatory and other various biological effects that exert in the prevention of various pathologies including cardiovascular diseases and cancer. Prevention of disease by polyphenols is mainly due to their antioxidative properties, however, reversal of epigenetic changes can have strong effects as well [11]. It has been experimentally confirmed that polyphenols not only prevent various diseases but also impact on the disease propagation, suppress progression and even contribute to the healing process [5,12]. In addition, some polyphenols exert hormonal actions and inhibitory effects on bone resorption [3]. Therefore, polyphenols now represent the main target of cancer research as they show potential for becoming superior agents for preventing and treating various malignancies [2]. Advantages of polyphenols as anticancer agents are their high accessibility, low toxicity, specificity of the response and various biological effects. A combination of cytoprotective effects toward normal cells and cytotoxic effects toward cancerous cells thus represents the main advantage of polyphenols as anticarcinogenic agents [12]. Their role in carcinogenesis lies in the regulation of growth factor-receptor interactions and cell signaling cascades that can induce cell cycle arrest and impact on cell survival and apoptosis of cancerous cells [13]. Polyphenols mainly induce apoptosis through pro-oxidative action that is exerted instead of their anti-oxidative action depending on their concentration, target molecule/s and environmental conditions [2,14,15]. For that reason, they may interact differently depending on the cell type: healthy versus cancerous one. Additionally, polyphenols help to establish the body’s immune system by inhibiting angiogenesis necessary for tumor growth and act as anti-inflammatory agents [13]. In the final stages of cancer, polyphenols attenuate the adhesiveness and invasiveness of cells therefore reducing their metastatic potential [13]. However, the bioavailability of polyphenols represents a big hurdle as they only reach the target organs in very low concentrations. One auspicious solution for this problem represents nanoformulation of polyphenols that has brought some promising results [13]. On the other hand, it may lead to a problem of toxicity of specific agents when administered in high doses [2]. It was for example shown that some extracted polyphenols in high concentrations act even in the opposite way: instead of preventing cancer they can contribute to its formation and progression [4,16,17]. In contrast, some studies have shown that when in combination with other polyphenols an individual polyphenol can exert significantly enhanced chemoprotective and other favorable properties at considerably lower concentrations [18,19]. Synergistic action of polyphenolic mixtures additionally results in the concurrent impact on different disease pathways consequentially contributing to a faster and more effective healing [19]. Polyphenols can also suppress the side effects of certain therapies already used in the cancer treatment like chemotherapy and radiotherapy and enhance their action [18]. Dietary polyphenols are predominantly present in glycosylated forms with one or more sugar residue conjugated to a hydroxyl group or the aromatic ring (flavanols are one notable exception) [20,21]. This represents the main reason for their low absorption in the stomach as only aglycones and some glucosides can be absorbed in the small intestine, the rest are absorbed in the colon [20]. In comparison to the intestine, the colon does not readily absorb polyphenols. This also leads to longer absorption times, which can be up to 9 h [20]. The efficiency of colon-absorbed polyphenols reaches only 15%–20% of total polyphenol content being absorbed in the intestine [20]. Glucosides in food sources of polyphenols thus enable faster and more efficient absorption of polyphenols [20]. However, the aglycones of some isoflavones showed superior absorption to their glucosylated

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