Effect Of Extracts Of Ophiopogon Japonicas On Drug Metablic Enzyme CYP3A4 Induction

Traditional Chinese Medicines (TCMs) are gaining more and more popularity in Asian countries including China, Japan and Korea, which are considered a complementary or alternative choice in the hope of promoting health and treating different kinds of diseases. The incorporation of herbal therapy into main medical regimen also has been encouraged by the western countries. For a long time, the use of herbal medicinal products depends on clinical practice. It is thought that herbal medicines to be natural and therefore safe, but this is a dangerous oversimplification. Actually, TCMs also have been associated with adverse effects including interactions with co-administered drugs, but literature in this field is limited. TCM formulas with fixed combinations rely on "sovereign, minister, assistant and guide", leading to greater challenges for the evaluation of herb-drug interactions (HDIs) compared with the synthetic drugs. Therefore, cautions should be taken when TCMs were co-administered with prescribed medications. In addition, it is well documented that variations in cultivation region, environmental and growing conditions have potential impacts on properties of TCMs. Previously, the ethanol extract of Maidong (also known as Ophiopogon japonicas) 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 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 stronger CYP3A4-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.