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Use of silkworms for identification of drug candidates having appropriate pharmacokinetics from plant sources
Yukihiro Asami1, Ryo Horie, Hiroshi Hamamoto
1Department of Microbiology, Faculty of Pharmaceutical Sciences, Graduate of the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan.
Background:
We use silkworms to evaluate therapeutic effects of drug candidates. Our previous reports have revealed that there are common mechanisms of pharmacokinetics of chemicals in silkworms and mammals. In this report, we attempt to establish a method by using silkworms to identify chemicals from plant extracts which are absorbed from intestine and also stably exist in body fluids.
Results:
Three compounds were detected in the silkworm hemolymph by HPLC analysis after midgut injection of acetone extracts of seihi, an herbal medicine obtained from orange peel. Analyses with MS and NMR revealed that the compounds were nobiletin, heptamethoxyflavone, and tangeretin. These compounds are reported to be stable in mammalian blood. The half-life of each of these compounds in the silkworm hemolymph was 18, 26 and 34 h, respectively.
Conclusions:
These findings suggest that silkworms can be used as a model animal to easily identify compounds with appropriate pharmacokinetic behavior.
