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

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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.

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