Arterial thrombotic diseases such as myocardial infarction and stroke are the leading cause of death in the U.S. Their socioeconomic and psychological impacts are immense. Drugs that can efficaciously reduce or eliminate these diseases are of great clinical importance and should have major commercial applications. Unfortunately efficacious drugs are limited. We consider it important to develop new anti-thrombotic drugs. In our pilot work we have identified anti-platelet properties in the ethanol-soluble fraction of a Chinese fungus, Cordyceps sinensis. The fraction exhibited inhibitory activity against platelet aggregation and secretion. Its inhibitory effect appears to be independent of thromboxane A2 and may be related to cAMP elevation. We propose in this SBIR application to purify the active component, evaluate its biological activity, elucidate its mechanism of action and assess its anti- thrombotic efficacy. The Phase I study will determine the feasibility of the purifying procedures and testing anti-platelet properties. We plan to carry out a sequence of solvent-solvent extractions which have been developed in our laboratory and is effective in segregating active compounds on the basis of their polarity into one or two highly enriched fractions. The inhibitory effect of the concentrated fractions on platelet aggregation and secretion will be evaluated in a lumiaggregometer. The fractions will be then processed by step-by-step procedures to isolate the active component. The Phase I study will lay the foundation essential for the full development of the active component into anti-thrombotic drugs in Phase II and subsequent clinical studies.
