(Applicant's Abstract): The use of dietary supplements containing botanical products is rapidly expanding the United States. While the public is using these products for a wide range of health related problems, the safety and efficacy of the products and of their active ingredients have not been tested. Depending on the supplement, limited or no scientific data are available that address the site)s) of action of the botanical products. Major active compounds of several commonly used botanicals have been purported to have anti-inflammatory actions and to be effective in treatment of arthritis or other chronic inflammatory diseases. These include Curcuma longa rhizome (powdered turmeric root), Zingiber officinale rhizome (powdered ginger root) and the gum resin of Boswellia serrata (boswellin). The overall goal of this project is to determine the active components of these botanicals and their effect on inflammatory mediators as well as to determine their ability to regulate inflammation. The effect of the botanicals on the production of inflammatory mediators will be first evaluated in vitro as part of this project followed in an animal model and in human subjects (Research Projects 2 and 3) after ingestion of the compounds/botanicals. Targeted botanicals will be initially screened through sensitive and selective in vitro bioassay systems against inflammation. Specific Aim 1. Chemically characterize the botanical components responsible for anti-inflammatory activity for in vivo studies in animal models and human subjects as part of Research Project 2 and 3. Analytical methods will be developed for quality control and for the quantification of the active components which will be also chemically identified. Specific Aim 2. Determine the in vitro effects of botanical compounds on the ability of macrpohages to produce inflammatory mediators. Evaluate potential sites of action of the botanicals. Dose-response data will be obtained using in vitro exposure of compounds to macrophages. Production of cytokines and mediators involved in inflammation will be determined from basal and stimulated cells. Preliminary screens will be performed using tumor necrosis factor alpha (TNF-alpha), prostaglandin-E2 )PGE2), and interleukin-10 (IL-10) as indicators. Altercations in transcription factor activation will be examined as a site of action for the botanicals. Specific Aim 3. Determine the in vivo effective of standardized botanical extracts on the ability of macrophages to produce inflammatory mediators. Monocytes will be isolated from animals that have been given the botanical compounds in their diet. Basal and stimulated production of mediators will be determined in vitro. Data will be correlated with the levels of botanical components found in the blood and with dose-response data from Specific Aim 2. Specific Aim 4. Determine, in humans the effect of botanical compounds on the production of inflammatory mediators. Monocytes will be isolated from human subjects who have been given the botanical compounds in their diets. The ability of the supplements to inhibit inflammatory mediator production will be evaluated, in vitro. Blood levels of mediators will also be determined. Specific Aim 5. Track the chemical and biological studies with an integrated natural products database system called NAPIS (NAtural Products Information System). This informatics system will link all the information together in easy to query database to promote the efficient and expedient analysis of the voluminous data generated from the chemical, in vitro and in vivo studies.