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.
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.
Saito
Junichiro
J
Drug Safety Research Laboratories, Astellas Pharma Inc. junichiroh.saitho@jp.astellas.com
Fukushima
Hiroko
H
Nagase
Hisamitsu
H
D000818:Animals; D016587:Antimutagenic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001713:Biphenyl Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry*; D020835:Medicine, Kampo; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D024301:Plant Bark / Q000737:chemistry
D016587:Antimutagenic Agents; D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D017705:Lignans; D009153:Mutagens; C005498:magnolol; D001564:Benzo(a)pyrene; D019363:Cytochrome P-450 CYP1A1