Chinese herbal therapy (CHT) has been used in China and other Asian countries for centuries. In CHT, the most widely used medicines are mixtures of many herbs, prepared according to Traditional Chinese Medicine (TCM) formulation concepts. It is believed that complex interactions produce synergistic effects and reduce possible side effects from some of the herbs. Because of its reputed efficacy, safety and relatively low cost, there is increasing use of CHT in western countries. Some scientific research results, including ours, provide evidence of efficacy and safety of CHT for treating allergy and asthma. In recent years, the US FDA and National Center for Complementary and Alternative Medicine (NCCAM)/NIH have provided guidance on standardization and quality control and support for botanical product investigation to facilitate botanical drug development in the US. However, the complexity of traditional Chinese herbal formulas containing many often poorly characterized chemical constituents makes standardization of herbal products challenging. In an attempt to improve quality control while maintaining therapeutic efficacy and safety, we recently reduced our original 14 herb mixture to a 3 herb mixture (ASHMI) which, in preliminary studies, is equally effective as the original formula, MSSM-002, for treating asthma in an animal model. However, the active ingredients are unknown. We recently have generated HPLC fingerprints, and sufficient data of Chemistry, Manufacture and Control data and documents (CMC) of ASHMI, and along with clinical and preclinical data under the Administrative core's coordination, we have submitted an IND application (IND#71526 under review). This project is designed to investigate possible synergy or potentiation both between the three herbal components, and between the constituents of each individual herb in vitro or ex vivo, to determine which constituents of the formula are most likely responsible for ASHMI's various biological effects, to chemically characterize these constituents, and to characterize, in mice, the pharmacokinetics of relevant biologically active constituents of ASHMI and to assess the postulated synergy among bioactive constituents in ASHMI in vivo in conjunction with project #1. Completing this project wiliprovide with us important data on the chemical and biological characteristicsof the ASHMI thatwill-result in rapid, effective, reproducible standardization methods for ASHMI herbal product. This study, in conjunction with the study in Project #1 and #2 may provide mechanisms to explain how ASHMI has wide range beneficial actions on allergic asthma process. The studies of pharmacokinetics of ASHMI in mice could lead to the ability to evaluate human pharmacokinetics and eventually permit rational alterations and simplifications in effective dosing regimens. Ultimately, achievement of this project together with those in the projects #1 and #2 may lead to an effective and safe CHT for asthma and provide insight into the mechanisms underlying ASHMI therapeutic effect on asthma.
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