Yoo, Hye Hyun Lee, Sang-Hyun Jin, Changbae Kim, Dong-Hyun 2024-01-20T23:03:59Z 2024-01-20T23:03:59Z 2022-02-17 2008-06 0032-0943 https://pubs.kist.re.kr/handle/201004/133405 The purpose of this investigation is to characterize the inhibition of CYP3A4 by methylenedioxyphenyl lignans isolated from Acanthopanax chiisanensis. Inhibition of CYP3A4 by three methylenedioxyphenyl lignans, avinin, helioxanthin, and 3-(3 '',4 ''-dimethoxybenzyl)-2-(3',4'-methylenedioxybenzyl)butyrolactone was time-, concentration-, and NADPH-dependent and characterized by K-1 values of 2.4, 1.6, and 2.2 mu M and k(inact) values of 0.030, 0.043, and 0.047 min(-1) respectively. The inhibition of CYP3A4 activity by these lignans was suppressed in the presence of a competitive CYP3A4 substrate, ketoconazole. Addition of nucleophiles or reactive oxygen scavenger and dialysis did not prevent inactivation of CYP3A4 by the Acanthopanax lignans. The loss of CYP3A4 enzymatic activity resulting from incubation with the Acanthopanax lignans was accompanied with a spectral loss of CYP3A4. These results collectively demonstrate that savinin, helioxanthin and 3-(3 '',4 ''-dimethoxybenzyl)-2(3',4'-methylenedioxybenzyl)butyrolactone from A. chiisanensis inactivate CYP3A4 in a mechanism-based mode. English Georg Thieme Verlag Mechanism-based inactivation of cytochrome P450 3A4 by methylenedioxyphenyl lignans from Aconthoponox chiisonensis Article 10.1055/s-2008-1074556 1 Planta Medica, v.74, no.8, pp.822 - 827 Planta Medica 74 8 822 827 N scopus 000257710700006 2-s2.0-47249098435 Plant Sciences Chemistry, Medicinal Integrative & Complementary Medicine Pharmacology & Pharmacy Plant Sciences Pharmacology & Pharmacy Integrative & Complementary Medicine Article COMPLEX-FORMATION ACANTHOPANAX-CHIISANENSIS GRAPEFRUIT JUICE INHIBITION EXTRACT Acanthopanax chiisanensis Araliaceae methylenedioxyphenyl lignans CYP3A4 mechanism-based inactivation