title: Ophiopogon japonicusstrains from different cultivation regions exhibit markedly different properties on cytotoxicity, pregnane X receptor activation and cytochrome P450 3A4 induction.
abstract: Maidong, known asOphiopogon japonicus, is one of the two basic ingredients of Shenmai injection, which is a widely used herbal preparation in traditional Chinese medicine (TCM) for the treatment of atherosclerotic coronary heart disease and viral myocarditis. Previously, the ethanol extract of Maidong activated the pregnane X receptor (PXR) signaling pathway and induced the cytochrome P450 3A4 (CYP3A4) reporter gene and raised the concern of herb-drug interactions (HDIs) when Maidong was used in combination with prescribed drugs metabolized by CYP3A4. Therefore, the present study further investigated and compared the differences of the ethanol and aqueous extracts (ee- and ae-, respectively) of two Maidong strains, known as Zhe Maidong (ZM) and Chuan Maidong (CM). Cytotoxicity, PXR activation and CYP3A4 induction by the 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-diphenytetrazoliumromide assay, reporter gene assay and reverse transcription-quantitative polymerase chain reaction analysis were examined. The observations showed that ee-ZM demonstrated a significantly higher cytotoxicity, a relatively weaker PXR activation capability and a markedly strongerCYP3A4-inducing capacity than ee-CM. Compared to ae-CM, ae-ZM exhibited only a slight or no difference on cytotoxicity and CYP3A4 induction, while a significant lower level of PXR activation was apparent. Collectively, Maidong from different producing areas possess different properties upon cytotoxicity and the drug-metabolizing enzyme inducing effect, and attention should be paid to the selection of Maidong strains from different planting regions into TCM preparations for reducing potential adverse reactions and HDIs.
authors.affiliation: Department of Pharmacy, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: LE-LE
authors.initials: LL
authors.lastname: Ge
authors.affiliation: Department of Pharmacy, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Lian-DI
authors.initials: LD
authors.lastname: Kan
authors.affiliation: Department of Pharmacy, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Zheng-Bing
authors.initials: ZB
authors.lastname: Zhuge
authors.affiliation: Department of Pharmacy, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: K E
authors.initials: KE
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Science, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Chen
keywords: Ophiopogon japonicus; cytochrome P450 3A4; herb-drug interactions; pregnane X receptor; traditional Chinese medicine