Use of silkworms for identification of drug candidates having appropriate pharmacokinetics from plant sources

Abstract

BackgroundWe 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.ResultsThree 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.ConclusionsThese findings suggest that silkworms can be used as a model animal to easily identify compounds with appropriate pharmacokinetic behavior.

A hyperglycemic silkworm model for evaluating hypoglycemic activity of Rehmanniae Radix, an herbal medicine

“…We previously reported that therapeutic effects and pharmacokinetics of chemicals, such as antibacterial, anti-fungal, anti-viral drugs, in silkworm were similar to that in mammals (3,4,(7)(8)(9)(10). Silkworm can be easily handled for evaluation of therapeutic activities of drug candidates using large numbers of individual animals with low costs.…”

Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph

“…Silkworm hemolymph and tissue can be harvested separately and used in biochemical, haematological, and immunological analyses [7,8]. Thus, the silkworm is an invertebrate model that can relieve the issues related to the use of mammals and thus promote pharmaceutical studies [7,9-12]. We previously demonstrated that the lethal dose of various cytotoxic substances in silkworms is consistent with that in mammals [7].…”

Animal welfare and use of silkworm as a model animal

“…Different models of the silkworm have already been established: bacterial infection model (13,14), baculoviral infection model (15), model to test innate immunity (16)(17)(18), diabetic model (19), bacterial virulence model (20)(21)(22), model to test pharmacokinetics (23), and model to test toxicity and metabolism (24). Most of these research projects have proven the correlation between results in mammals and silkworms.…”