Clinical trials testing the potential health benefits of immune enhancing dietary supplements have produced inconsistent results. A major problem contributing to these inconsistent outcomes is that these studies have used a wide variety of poorly characterized products. Attempts to solve this product quality control problem using chemical standardization methods has had limited success because physiochemical properties cannot fully predict the biological potency of the high molecular weight substances that are typically responsible for the immune enhancing effects of these supplements. The objective of this application is to develop services for standardizing the potency of a broad range of immune enhancing dietary supplements based on biological activity using technology developed by the University of Mississippi (UM). University of Mississippi has set-up a battery of in vitro assay systems capable of detecting different high molecular weight components that activate macrophages. The components detected by these bioassays are relevant for standardization because they impact immune parameters in vivo and are thought to be responsible for the therapeutic action of these products. The University of Mississippi has also developed methods to remove nuisance compounds that interfere with the detection of macrophage activation as well as methods for the preparation of extracts based on solvent-specific extractability of the active components.
The Specific Aims are as follows: 1. Prepare extracts from 8 different immune enhancing dietary supplements of commercial interest. Botanical raw material will be processed to remove nuisance compounds that interfere with detection of activity followed by preparation of three different types of extracts that concentrate different classes of active compounds. 2. Identify the in vitro bioassays to be used for biological standardization of each dietary supplement. Extracts prepared in Aim 1 will be assessed in a battery of three in vitro bioassays that detect potency of macrophage activation exhibited by the following activators: bioassay 1 (components from endophytic bacteria), bioassay 2 (polysaccharides) and bioassay 3 (inflammasome activators). Results will determine the appropriate bioassay and type of extract to be used for standardization of each dietary supplement. 3. Develop biological reference standards. Reference standards will be developed for each supplement that can be used to determine the potency of unknown samples and to define accuracy of each bioassay. Accomplishing these objectives will provide a valuable technology to quantitate the potency of immune enhancing dietary supplements so that these products can be manufactured to exhibit consistent therapeutic properties for consumers and for use in clinical trials. It is envisioned tht Phase II will define additional bioassay parameters, further establish the therapeutic relevance of the bioassay endpoints, and begin to offer services to standardize products based on bioactivity. This STTR application represents a collaborative effort between Phytochemical Services, Inc. (PSI) and the University of Mississippi National Center for Natural Products Research.
This application is directed towards improving the quality of immune enhancing dietary supplements by developing services to measure the biological potency of these products. Development of these services will impact human health by providing information to enable manufacturers to produce immune enhancing dietary supplements that are standardized to exhibit consistent therapeutic properties for consumers and for use in clinical trials.
