Beneficial and Adverse Effects of Natural Chemicals on Human Health and Food Safety

Non-Technical Summary:<br/>
Facilitated by comprehensive collaboration among participants, the overall goal of W-3122 is on improving food safety and human health worldwide. Research supported by W-3122 addresses the role that natural foodborne toxicants, cancer chemopreventives, botanical estrogens, dietary fiber, immune modulators and antimicrobials play in human health and disease. Understanding the complex relationship between dietary chemicals and human health remains a paramount concern to public and agrifood industry stakeholders. These stakeholders include consumers, agricultural producers, food processors, health professionals, and policy makers charged with maintaining a safe and nutritious food supply. Outputs:1.Consumer information on the beneficial and adverse impacts of bioactive, dietary chemicals on human health and chronic disease;2. Improved recommendations and guidelines for use of bioactive dietary compounds in herbal supplements and functional foods; 3.Improved hazard and risk assessment data are of dietary toxicants for policy makers; 4.Inform the American food industry on potential bioactive chemicals and fiber present in food ingredients that can benefit consumer health;5.Identification of novel value added crops and foods that can be exploited by farmers and processors, respectively; 6.Dissemination of data in scientific meetings and peer-reviewed journals; 7.Purified natural chemicals, complex mixtures (extracts) with biological activity, biological reagents such as antibodies, cell lines, RNA from treated cells and laboratory animals will be made available for further study to other W-3122 researchers. Outcomes or projected Impacts:1.Reducing cancer incidence and increasing safety by characterizing the beneficial and adverse effects of putative cancer protective substances from food. This information will assist the National Cancer Institute in selecting agents for clinical intervention trials, and the US-FDA and other regulatory agencies to regulate and properly evaluate the safety and effectiveness of certain widely used food supplements; 2.Improving human health by understanding and exploiting the role of dietary components on immune function. Dietary immunomodulation holds great promise for decreasing human morbidity and mortality from autoimmune diseases and immune suppression; 3.Benefitting growers, the American agrochemical industry, and improving the safety of the food supply by developing plant-food derived substances as safe, effective and economical antimicrobial and herbicidal agents; 4.Informing the American pharmaceutical industry by developing Brassica indoles and isoflavones as model gene targeting reagents for use in cancer therapy and prevention. These and other food constituents hold great promises as models for the development of safe, selective, and effective cancer protective.
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Approach:<br/>
Objective 1. Determine mechanisms of action by which dietary bioactive compounds protect against human diseases. MI will study the effectiveness on omega-3 fatty acids for mitigating toxicant- accelerated lupus nephritis as well as ascertain the appropriate dietary omega-3s levels required to counter triggering and exacerbation of lupus nephritis and other autoimmune diseases.
<br/>Objective 2 Elucidate mechanisms of action of dietary toxicants and develop biomarkers for human risk assessment and disease prevention. MI will used cloned cell lines and animal models for anorexia and emesis to understand the role of bitter taste receptors in mediating gastroenteritis and growth suppression by trichothecene mycotoxin congeners and other dietary toxicants. MI will cooperate with GA-USDA to determine how processing affects toxicity of the trichothecenes and reflected by cellular and animal models.
<br/>Objective 3. Discover and characterize novel bioactive compounds that have beneficial or adverse effects on human health. CA-B, MI and CA-D will collaborate on determining immune modulating effects of dietary indoles and natural products from Indonesian plants and microbes. The initial screens by CA-B of Indonesian flora will employ high-throughput, cell-based assays of extracts for anticancer and immune modulating activities. Following the activity-based chromatographic purification and spectral identification of active substances, the activities of purified compounds will be characterized more fully in studies to include rodent assays. For studies of the modes of action of the indoles and other purified natural products, CA-B will use gene expression microarray and immuno-protein array techniques to determine the kinetics and concentration-dependent effects of the purified compounds, on the expression in cultured tumor cells and immune cells of genes and proteins associated with tumor growth and immune regulation. Promoter analyses will be conducted of key genes implicated in anti-tumor progression activities of compounds to identify regulatory mechanisms for this process. The functional effects of implicated genes on in vitro and in vivo measures of immune response and tumor development will be assessed in rodents. CA-B will continue to cooperate with CA-D and MI in studies of the role of the Ah receptor in the immune enhancing effects of the Brassica indoles and other natural products. MI will conduct modeling studies to determine the relative potencies of the different trichothecenes in neurotoxic and immunotoxic endpoints to generate toxic potency factors that can be applied to risk assessment. MI will cooperate with HI to determine the role of bitter taste receptors in mediating anti-obesity and anti-diabetes effects of natural compounds in foods and supplements. MI will cooperate with CA and CA-B in determining bitter taste agonism in natural toxic and bioactive compounds.
<br/>Objective 4. Increase beneficial or decrease adverse effects of dietary constituents and microbes.