Effects of hot water extract from cultured Agaricus blazei (CJ-01) fruiting bodies on neurotransmitter receptors, transporters and hepatic drug-metabolizing enzymes

Effects of hot water extract from cultured Agaricus blazei (CJ-01) fruiting bodies (CJ-01 extract) on the neurotransmitter receptors, transporters and hepatic drug-metabolizing enzymes in rats were examined. Hot water extract was obtained by the extraction of CJ-01 (10 g/600 ml) at 80℃ for 1 h. CJ-01 extract had little effect or inhibitory effect only at high concentrations, on specific binding of each radioligand to label adrenoceptors (α, β), muscarinic cholinoceptors, Hi-histamine receptors, sigma receptors, TRH receptors, 5-HT_<2A> receptors, 1,4-dihydropyridine receptors, serotonin transporters, in rat tissues (brain, heart, prostate). On the other hand, relatively low concentrations of CJ-01 extract inhibited specific binding of [3^H]N^α-methylhistamine (NAMHA) (H_3-histamine receptor ligand) and [3^H]nisoxetine (noradrenaline transporter ligand) in rat brain, and their IC_<50> values were 0.3 and 10.1 mg/mL, respectively. The repeated oral administration of CJ-01 (0.15, 1.5 g/kg body weight/day) extract to rats for 5 weeks caused a significant increase of maximal number of binding sites (Bmax) for [3^H]NAMHA and a concomitant decrease of Bmax for [3^H]pyrilamine (H_1-histamine receptor ligand) in the brain, suggesting up regulation of H_3-histamine receptors and down regulation of Hi-histamine receptors. Furthermore, it has been shown that repeated oral administration of CJ-01 extract had little or slight (only at high concentration) effect on biochemical examination parameters in the blood, and also on the content of cytochrome P450 and on the activity of hepatic drug-metabolizing enzymes. In conclusion, the present study has shown that CJ-01 extract may contain relatively selective antagonist of H_3-histamine receptor which could block brain H_3-histamine receptors after the systemic administration. Also, it has been shown that repeated administration of CJ-01 extract may cause little toxic effect on the hepatic f unction and it may not influence significantly hepatic drug metabolism.