Relevance of phenolic antioxidants for functional food and comparative metabolic biology considerations

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It is clear that food plants are excellent sources of phenolic phytochemicals, especially as bioactives with antioxidant property. As is evident, phenolic antioxidants from dietary sources have a history of use in food preservation, however, many increasingly have therapeutic and disease prevention applications (69-72). Therefore, understanding the nutritional and the disease protective role of dietary phytochemicals and particularly phenolic antioxidants is an important scientific agenda well into the foreseeable future (73). This disease protective role pf phytochemicals is becoming more significant at a time when the importance of in the prevention of oxidation linked chronic diseases is gaining rapid recognition globally. Therefore, disease prevention and management through the diet can be considered an effective tool to improve health and reduce the increasing health care costs for these oxidation linked chronic diseases, especially in low income countries.

As discussed earlier, phenolic phytochemicals have been associated with antioxidative action in biological systems, acting as scavengers of singlet oxygen and free radicals (7477). Recent studies have indicated a role for phenolics from food plants in human health and, in particular, cancer (76,78). Phenolic phytochemicals (i.e., phenylpropanoids) serve as effective antioxidants due to their ability to donate hydrogen from hydroxyl groups positioned along the aromatic ring to terminate free radical oxidation of lipids and other biomol-ecules (79). Phenolic antioxidants, therefore, short circuit destructive chain reactions that ultimately degrade cellular membranes. Examples of food based plant phenolics that are used as antioxidant and antiinflammatory compounds are curcumin from Curcuma longa (80-82), Curcuma mangga (83), and Zingiber cassumunar (84), and rosmarinic acid from Rosmarinus officinalis (72,85). Examples of phenolics with cancer chemopreventive potential are curcumin from Curcuma longa (80,86-89), isoflavonoids from Glycine max (90-92), and galanigin from Origanum vulgare (93). Other examples of plant phenolics with medicinal uses include lithospermic acid from Lithospermum sp. as antigonadotropic agent (94), salvianolic acid from Salvia miltiorrhiza as an antiulcer agent (95), proanthocyanidins from cranberry to combat urinary tract infections (96,97), thymol from Thymus vulgaris for anticaries (98), and anethole from Pimpinella anisum as an antifungal agent (99).

We have targeted enhanced production of oxidation disease relevant plant biphenyl metabolites such as rosmarinic acid, resveratrol, ellagic acid, and curcumin using novel tissue culture and bioprocessing approaches. Other phenolic phytochemicals also targeted are flavo-noids, quercetin, myrcetin, scopoletin, and isoflavonoids. Among simple phenolics, there is major interest in the overexpression of l-tyrosine and l-DOPA from legumes in a high phenolic antioxidant background (100,101). Rosmarinic acid has been targeted from clonal herbs (1,69) for its antiinflammatory and antioxidant properties (85,102,103). Resveratrol has shown antioxidant and cancer chemopreventive properties (104,105) and its overproduction has been targeted from several fruits using solid-state bioprocessing (106,107). Ellagic acid has been targeted for antioxidant and cancer chemopreventive properties (108,109) and has been similarly targeted via solid-state bioprocessing from fruits and fruit processing byproducts (106). Extensive studies have shown cancer chemopreventive and antioxidant properties for Curcuma longa and its major active compound, curcumin, (81,86,110) and the developmental and elicitor stress mediated overexpression of curcumin is being investigated.

The emergence of dietary and medicinal applications for phenolic phytochemicals, harnessing their antioxidant and antimicrobial properties in human health and wellness has sound rationale. As stress damage on the cellular level appears similar among eukaryotes, it is logical to suspect that there may be similarities in the mechanism for cellular stress mediation between eukaryotic species. Plant adaptation to biotic and abiotic stress involves the stimulation of protective secondary metabolite pathways (111-113) that results in the biosynthesis of phenolic antioxidants. Studies indicate that plants exposed to ozone responded with increased transcript levels of enzymes in the phenylpropanoid and lignin pathways (114). Increase in plant heat tolerance is related to the accumulation of phenolic metabolites and heat shock proteins that act as chaperones during hyperthermia (115).

Phenolics and specific phenolic-like salicylic acid levels increase in response to infection, acting as defense compounds, or to serve as precursors for the synthesis of lignin, suberin, and other polyphenolic barriers (116). Antimicrobial phenolics called phytoalexins are synthesized around the site of infection during pathogen attack and, along with other simple phenolic metabolites, are believed to be part of a signaling process that results in systemic acquired resistance (111-113). Many phenylpropanoid compounds such as flavo-noids, isoflavonoids, anthocyanins, and polyphenols are induced in response to wounding (117), nutritional stress (118), cold stress (119), and high visible light (120). UV irradiation induces light-absorbing flavonoids and sinapate esters in Arabidopsis to block radiation and protect DNA from dimerization or cleavage (121). In general, the initiation of the stress response arises from certain changes in the intracellular medium (122) that transmit the stress induced signal to cellular modulating systems and results in changes in cyto-solic calcium levels, proton potential as a long distance signal (123), and low molecular weight proteins (124). Stress can also initiate free radical generating processes and shift the cellular equilibrium toward lipid peroxidation (125). It is believed that the shift in prooxidant-antioxidant equilibrium is a primary nonspecific event in the development of the general stress response (126). Therefore, protective phenolic antioxidants involved in such secondary metabolite linked stress responses in food plant species has potential as a source of therapeutic and disease-preventing functional ingredients for oxidation disease linked diet (high carbohydrate and high fat diets) and environment (physical, chemical, and biological) influenced chronic disease problems (69).

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