Complementary and alternative systems of medicine involve, and the American public routinely uses, complex botanical products for health maintenance, disease prevention, and as treatments. There is an underlying system of belief, yet relatively little supportive biomedical evidence, that the polypharmacy of complex botanicals provides distinct advantages over single-ingredient drugs. One underlying theoretical paradigm is that primary active ingredients in complex botanicals act synergistically with secondary compounds. Another is that secondary compounds mitigate the undesirable side effects caused by the predominant active ingredients. A third possibility is that multiple ingredients act through multiple discrete pathways to impact the host, and that lower concentrations of each ingredient can therefore be more efficacious when used together than they would be individually. If true, these theories could explain and justify complex botanical actions in natural products, and thus studies are needed to demonstrate their mechanisms of action and veracity. However, before supporting such trials, several issues regarding the choice of the clinical trial material require special attention, for example: (1) use of different parts of the plants (e.g., roots, aerial parts, whole plant); (2) optimal growing and harvest conditions; (3) whether to use whole extract or a specific fraction; (4) the method of extraction; (5) chemical standardization; (6) presentation of the medication. This project responds to the stated needs of NIH/NCCAM by proposing to evaluate the feasibility of producing research grade products from the popular botanical Hydrastis canadensis Linn., commonly known as goldenseal. Even though Hydrastis has been used extensively in traditional medicine and goldenseal is currently one of the top 20 herbal products sold in the US, both as a single species preparation and in combination with others such as Echinacea, there have been no published clinical studies to verify or disprove its safety and/or effectiveness. The lack of well characterized, standardized Hydrastis products has been a primary obstacle to the initiation of studies regarding this plant. Work from two previous Phase I and II USDA SBIR awards combined with data produced by this proposal will answer the above basic questions and provide high quality standardizeable raw material which we will use to carry the research a step further and challenge the paradigm of chemical marker only standardization by evaluating the feasibility of utilizing biological activity as a complementary standard by which to measure the potency of Hydrastis products. Phase I will result in a well-defined product with a constant level of bioactivity which could then be used in Phase II to assess bioavailability, pharmacology, and pharmacokinetics of selected constituents as well as stability testing and bioavailability among the different products. The end result of Phase II will be the capability to provide the standardized Hydrastis products to NIH-sponsored pre-clinical and clinical trials in order to establish the efficacy and safety of Hydrastis in reducing the incidence and severity of certain gastrointestinal disorders. The development and use of standardized Hydrastis products in research will (1) allow for comparisons across studies using the same products, (2) allow for comparisons between known products, and (3) lead to subsequent, large randomized controlled clinical trials. A reliable and constant source for these products will assure the quality of study outcomes. ? ? ?
