Biological Function Of Phenolic Phytochemicals

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Reactive oxygen species (ROS) are now associated with manifestation of several oxidation-linked diseases such as cancer, cardiovascular diseases (CVD) and diabetes; epidemiologi-cal studies indicate that diets rich in fruits and vegetables are associated with lower incidences of such oxidation linked diseases. These disease protective effects of fruits and vegetables are now linked to the presence of antioxidant vitamins and phenolic phyto-chemicals having antioxidant activity, which support the body's antioxidant defense system (12-15). This has led to an interest in the use of diet as a potential tool for the control of these oxidative diseases (5,16-18). This is further supported by recent in vitro and clinical studies which have shown that lack of physical activity, exposure to environmental toxins, and consumption of diets rich in carbohydrate and fats induced oxidative stress, which was decreased by consuming fruits, vegetables, and their products (19-26).

Phenolic phytochemicals with antioxidant properties are now widely thought to be the principle components in fruits, vegetables, and herbs that have these beneficial effects. Most phenolic phytochemicals that have positive effect on health are believed to be functioning by countering the effects of reactive oxygen species (ROS) species generated during cellular metabolism. Consumption of natural dietary antioxidants from fruits, vegetables, and herbs has been shown to directly enhance scavenging of ROS, prevent the formation of ROS, and enhance the function of the antioxidant defense response mediated by Glutathione, Ascorbate, superoxide dismutase (SOD), catalase (CAT), and glutathi-one-s-transferase (GST) interface (15-20).

Specifically, oxidation of biological macromolecules as a result of free radical damage has now been strongly associated with development of many physiological conditions that can manifest into disease (27-31). The first and widely accepted mode of action of these phenolic phytochemicals in managing oxidation stress related diseases is due to the direct involvement of the phenolic phytochemicals in quenching the free radicals from biological systems. Phenolic phytochemicals, due to their phenolic ring and hydroxyl substituents, can function as effective antioxidants due to their ability to quench free electrons and chelate metal ions that are responsible for generating free radicals (32). Phenolic antioxidants can therefore scavenge the harmful free radicals and thus inhibit their oxida-tive reactions with vital biological molecules (32).

Emerging research into the biological functionality of phenolic phytochemicals also strongly suggests their ability to modulate cellular physiology both at the biochemical/ physiological and at molecular level. Structural similarities of phenolic phytochemicals with several key biological effectors and signal molecules have been suggested to be involved in induction and repression of gene expression or activation and deactivation of proteins, enzymes, and transcription factors of key metabolic pathways (27,33-35). They are believed to be able to critically modulate cellular homeostasis as a result of their phys-iochemical properties such as size, molecular weight, partial hydrophobicity, and ability to modulate acidity at biological pH through enzyme (dehydrogenases) coupled reactions. As a consequence of many modes of action of phenolic phytochemicals they have been shown to have several different functions. Potential anticarcinogenic and antimutagenic properties of phenolic phytochemicals such as gallic acid, caffeic acid, ferulic acid, catechin, quercetin, and resveratrol have been described in several studies (36-38). It is believed that phenolic phytochemicals might interfere in several of the steps that lead to the development of malignant tumors, including, inactivating carcinogens, inhibiting the expression of mutant genes (39). Many studies have also shown that these phenolic phytochemicals can repress the activity of enzymes such as cytochrome P 450 (CYP) class of enzymes involved in the activation of procarcinogens. Their protective functions in liver against carbon tetrachloride toxicity (40) have shown that phenolic phytochemicals also decrease the carcinogenic potential of a mutagen and can activate enzymatic systems (Phase II) involved in the detoxification of xenobiotics (41). Antioxidant properties of the phenolic phytochemicals linked to their ability to quench free radicals has been shown to prevent oxidative damage to the DNA which has been shown to be important in the age related development of some cancers (42). Phenolic phytochemicals have been shown to inhibit the formation of skin tumors induced by 7, 12-dimethyl-benz(a) anthracene in mice (43). Skin tumors in mice, and development of preneoplastic lesions in rat mammary gland tissue in cultures in the presence of carcinogens, were inhibited by resveratrol which is an important biphenyl found in wine (44,45).

Ability of phenolic phytochemicals is preventing of cardiovascular diseases (CVD) has been well described by epidemiological studies. The "French paradox" describes a famous study linking the lower incidences of CVD in the population consuming wine as part of their regular diet (46). Recent research has revealed that these beneficial effects of wine are due to the presence of a biologically active phenolic phytochemical "resveratrol." Inhibiting of LDL oxidation (47) and preventing platelet aggregation (48) are now believed to be the mechanisms by which resveratrol and other phenolic antioxidants prevent development of CVD. Phenolic phytochemicals have also been able to reduce blood pressure and have antithrombotic and antiinflammatory effects (48,49). Phenolic phytochemicals have also been shown to inhibit the activity of alpha-amylase and alpha-glucosidase which are responsible for postprandial increase in blood glucose level, which has been implicated in the manifestation of type-II diabetes and associated cardiovascular diseases (50,51).

In addition to managing oxidation linked diseases, immune modulatory activities of phenolic phytochemicals such as antiallergic (52) properties as a result of suppressing the hypersensitive immune response have also been defined. Antiinflammatory responses mediated by suppression of the TNF-alpha mediated proinflammatory pathways were also shown to be mediated by phenolic phytochemicals (53). Several studies have shown phenolic phytochemicals to have antibacterial, antiulcer, antiviral, and antifungal properties (54-57) and therefore are being implicated in management of infectious diseases.

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