Abstract PL05-03: Influence of Mother Nature’s pharmacopeia on everyday health and wellbeing

Abstracts: Frontiers in Cancer Prevention Research 2008 PL05-03 Natural products have played and continue to play a dominant role in pharmaceutical care. Over half of the drugs approved by the FDA during the past several years have a natural product relationship (1). In addition, a variety of individual natural products found in the diet of human beings are capable of mediating physiological responses. Especially notable are dietary agents associated with cancer chemopreventive activities, such as sulforaphane and isothiocyanates (cruciferous vegetables), epigallocatechin-3-gallate (green tea), curcumin (turmeric), sulfur-containing compounds and selenium (the genus Allium ), and lycopene (tomatoes) (2). One of the most highly studied agents in this category is resveratrol. A simple stilbene, known for many years, gained significant attention when the potential for mediating cancer chemopreventive activity was demonstrated (3). Since that time, approximately 2,000 papers have been published (4), and a raft of biological activities have been demonstrated or studied, such as radioprotection, antifungal, antibacterial, antiviral, prevention of aging and age-related diseases, neuroprotection, cardioprotection, and anti-inflammation (5). A key reason resveratrol has gained such notoriety is due to its occurrence in the grape. Interestingly, however, in addition to resveratrol and resveratrol derivatives, over 1,600 phytochemicals are components of the grape, and research with whole grapes or grape powder has suggested cardiovascular benefits, cancer chemopreventive activity, as well as effectiveness against less prevalent but devastating illnesses, such as Alzheimer disease and urinary bladder dysfunction (6). Even more broadly, it is clear that a well balanced diet, rich in fruits and vegetables, can help to preserve everyday health and wellbeing. In this sense, diet may be viewed as a massive pharmacopeia, Mother Nature’s pharmacopeia, comprised of thousands of natural products. A fundamental question addressed by drug development programs is how test agents function on a molecular level, but definitive mechanisms of action are generally not available despite decades of exhaustive research, even with single agents (7). This is profusely evident based on the myriad of biological responses that have been observed at the cellular level, and even more overwhelming when considering gene expression data that are now available. Obviously, the situation is confounded even further when thousands of agents are used in combination, which is virtually always the case when considering dietary sources and “traditional medicines”. Definitive answers concerning clinical efficacy are only available through human trials, but this is not very satisfying from an intellectual point-of-view nor easily achieved with poorly characterized mixtures of components. Now that the enormity of the issue has been at least recognized, a fresh approach is required that recognizes the proper level of complexity required to capture key biological interactions between components in the natural product while providing for its unambiguous characterization. A promising strategy is found in the model-based informatics domain consisting of a novel framework called an ontology that exploits recent progress in information and knowledge management methodologies and tools (8). An ontology potentially links models of biological action to the data in a form suitable for inclusion in computational tools. This is accomplished by factoring the model into key concepts while preserving the context of the disparate and copious data. By so extracting the knowledge from the complex and varied data and models, there is hope of understanding the wisdom of Nature and advancing pharmaceutical product development in an enlightened manner. (Supported by program project P01 48112 awarded by the National Cancer Institute) Citation Information: Cancer Prev Res 2008;1(7 Suppl):PL05-03.