PMID- 19571387 OWN - NLM STAT- MEDLINE DCOM- 20091008 LR - 20190720 IS - 0918-6158 (Print) IS - 0918-6158 (Linking) VI - 32 IP - 7 DP - 2009 Jul TI - Anti-clastogenic effect of magnolol-containing Hange-koboku-to, Dai-joki-to, Goshaku-san, and Magnoliae Cortex on benzo(a)pyrene-induced clastogenicity in mice. PG - 1209-14 AB - Magnolol was previously shown to inhibit genotoxicity induced by environmental mutagens both in vitro and in vivo. Here, we investigate the effects of the magnolol-containing kampo (traditional) medicines Hange-koboku-to, Dai-joki-to, and Goshaku-san, as well as Magnoliae Cortex, on the clastogenesis induced by benzo(a)pyrene (B(a)P) using the mouse micronucleus test. The mice were first treated with a single intraperitoneal injection of B(a)P, followed by a single oral dose of Hange-koboku-to, Dai-joki-to, Goshaku-san, or Magnoliae Cortex. Peripheral blood specimens were prepared 48 h after B(a)P administration and analyzed using the acridine orange (AO) technique. The anti-clastogenic mechanisms employed by the kampo medicines and Magnoliae Cortex were also investigated by evaluating in vivo CYP1A1 activity using the zoxazolamine paralysis test. Results show that Hange-koboku-to, Dai-joki-to, and Magnoliae Cortex, which contain high levels of magnolol, significantly inhibited the clastogenesis induced by B(a)P and sufficiently inhibited in vivo CYP1A1 activity. In contrast, Goshaku-san, which contains low levels of magnolol, had little inhibitory effect on clastogenicity and in vivo CYP1A1 activity. These findings suggest that magnolol is a major contributor to the inhibition of B(a)P-induced clastogenesis, and that kampo medicines exert significant anti-clastogenic effects. FAU - Saito, Junichiro AU - Saito J AD - Drug Safety Research Laboratories, Astellas Pharma Inc. junichiroh.saitho@jp.astellas.com FAU - Fukushima, Hiroko AU - Fukushima H FAU - Nagase, Hisamitsu AU - Nagase H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - Biol Pharm Bull JT - Biological & pharmaceutical bulletin JID - 9311984 RN - 0 (Antimutagenic Agents) RN - 0 (Biphenyl Compounds) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Lignans) RN - 0 (Mutagens) RN - 001E35HGVF (magnolol) RN - 3417WMA06D (Benzo(a)pyrene) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) SB - IM MH - Animals MH - Antimutagenic Agents/isolation & purification/*pharmacology MH - Benzo(a)pyrene/*toxicity MH - Biphenyl Compounds/isolation & purification/*pharmacology MH - Cytochrome P-450 CYP1A1/antagonists & inhibitors MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal/isolation & purification/*pharmacology MH - Lignans/isolation & purification/*pharmacology MH - Magnolia/*chemistry MH - *Medicine, Kampo MH - Mice MH - Mice, Inbred ICR MH - Micronucleus Tests MH - Mutagens/*toxicity MH - Plant Bark/chemistry EDAT- 2009/07/03 09:00 MHDA- 2009/10/09 06:00 CRDT- 2009/07/03 09:00 PHST- 2009/07/03 09:00 [entrez] PHST- 2009/07/03 09:00 [pubmed] PHST- 2009/10/09 06:00 [medline] AID - JST.JSTAGE/bpb/32.1209 [pii] AID - 10.1248/bpb.32.1209 [doi] PST - ppublish SO - Biol Pharm Bull. 2009 Jul;32(7):1209-14. doi: 10.1248/bpb.32.1209.