ABSTRACT
<i>Objective</i>: Extract from cultured <i>Lentinula edodes</i> mycelia (L.E.M.) is a food ingredient possessing various pharmacologic actions such as immunomodulatory properties, antitumor and hepatoprotective effects. In Japan, it has been used as a health food for 30 years or more.<br> In the present study to evaluate the safety of L.E.M., a genotoxicity study and acute toxicity study were conducted. In addition, the inhibitory effect of drug-metabolizing enzyme by L.E.M. was tested<i> in vitro</i>, to gain insight on the interaction with medicines.<br> <i>Methods</i>: The genotoxicity study was performed using a bacterial reverse mutation assay and a <i>in vivo</i> mammalian bone marrow cell chromosomal mutation assay. The acute toxicity study was performed using a single-dose oral toxicity test in rats. Inhibitory activity of cytochrome P-450 3A4 (CYP3A4), one of the most important drug-metabolizing enzymes, by L.E.M. was tested using a baculovirus-expressed system.<br> <i>Results</i>: In the genotoxicity study, mutagenicity was negative for both bacterial reverse mutation assay and <i>in vivo</i> mammalian bone marrow cell chromosomal mutation assay. In the acute toxicity study, no toxic symptoms were observed by single dose oral administration of L.E.M. at a dose of 10,000 mg/kg BW in rats. This implies LD<sub>50</sub>>10,000 mg/kg BW. No inhibitory activity of CYP3A4 by L.E.M. was observed at in the <i>in vitro</i> screening system to investigate drug-L.E.M. interaction.<br> <i>Conclusion</i>: It is believed L.E.M. is a safety ingredient for foods used in complementary and alternative medicine, since it was toxicologically safe and showed no inhibitory activity of CYP3A4 in the studies conducted.<br>