Sho-saiko-to and Saiko-keisi-to, the traditional Chinese and Japanese herbal medicines, altered hepatic drug-metabolizing enzymes in mice and rats when administered orally for a long time.
As the consumption of herbal remedies has increased, the opportunity that such herbal medicines are co-administered with other drugs has also risen gradually and we are, therefore, very much concerned about herb-drug interactions. We examined the effects of pre-administration of Kampo medicines (Sho-saiko-to, Saiko-keishi-to, Shigyaku-san and Dai-saiko-to) on the pentobarbital-induced sleeping time in mice and rats, to clarify the possibility that they could affect the drug-metabolizing enzymes. The administration of Sho-saiko-to and Saiko-keishi-to for 4 weeks significantly shortened the pentobarbital-induced sleeping time in mice and the administration of Sho-saiko-to for 2 weeks significantly reduced the sleeping time in rats. Furthermore, we tried to identify the molecular species of rat cytochrome P450s (CYPs) affected by Sho-saiko-to and Saiko-keishi-to by competitive RT-PCR. The oral administration of Sho-saiko-to for 2 weeks upregulated the mRNA expression of CYP2B, CYP3A1, CYP2E1 and CYP4A1 in rats. The treatment with Saiko-keishi-to for 2 weeks also up-regulated the mRNA expression of CYP2B, CYP3A1 and CYP4A1. Sho-saiko-to and Saiko-keishi-to may potentially influence the drug-metabolizing enzymes in man, and would thus require much attention when used in the clinical situation.
Nose
Mitsuhiko
M
Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. nose@phar.nagoya-cu.ac.jp
Tamura
Masayo
M
Ryu
Nobukazu
N
Mizukami
Hajime
H
Ogihara
Yukio
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D010634:Phenobarbital / Q000493:pharmacokinetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000187:drug effects; D015854:Up-Regulation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D006993:Hypnotics and Sedatives; D012333:RNA, Messenger; C461320:shosaiko-to; C018142:saiko-keishi-to; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital