Herb-Drug Interaction of 50 Chinese Herbal Medicines on CYP3A4 Activityin Vitroandin Vivo

Abstract

The purpose of this study is to evaluate the effects of Chinese herbal medicines on the enzymatic activity of CYP3A4 and the possible metabolism-based herb-drug interactions in human liver microsomes and in rats. Fifty single-herbal preparations were screened for the activity of CYP3A4 using human liver microsomes for an in vitro probe reaction study. The enzymatic activity of CYP3A4 was estimated by determing the 6β-hydroxytestosterone metabolized from testosterone performed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Huang Qin (Scutellaria baicalensis Geprgi), Mu Dan Pi (Paeonia suffruticosa Andr.), Ji Shiee Terng (Spatholobus suberectus Dunn.) and Huang Qi (Astragalus membranaceus [Fisch] Bge) have been demonstrated to have remarkable inhibiting effects on the metabolism of CYP3A4, whereas Xi Yi Hua (Magnolia biondii Pamp.) exhibited a moderate inhibition. These five single herbs were further investigated in an animal study using midazolam. Mu Dan Pi, Ji Shiee Terng and Huang Qi were observed to have greatly increased in the C(max) and AUC of midazolam. This study provides evidence of possible herb-drug interactions involved with certain single herbs.

Dietary Flavonoids Modulate CYP2C to Improve Drug Oral Bioavailability and Their Qualitative/Quantitative Structure–Activity Relationship

“…RLMs were prepared as previously described, with slight modifications (27). Microsomes were obtained from 10 g liver samples of 8-week-old SD rats using the differential centrifugation technique.…”

The significant inhibition on CYP3A caused by radix Aconiti single herb is not observed in the Wutou decoction: The necessity of combination therapy of radix Aconiti

“…glycyrrhizin could increase CYP3A activity and mRNA levels in rats (Miao et al, 2014) and in Swiss Albino CD1 mice (Paolini et al, 1998). Radix Astragali showed remarkable inhibitory effect on the activity of CYP3A4 in human liver microsomes and in rats (Pao et al, 2012). Only a slight inhibitory effect was observed when the rats were exposed to the extract of Radix Paeoniae Alba (Weng et al, 2010).…”

Liver toxicity during temozolomide chemotherapy caused by Chinese herbs

“…The detailed list of herbs taken by our patient is shown in Table 1 and comprises at least two herbs Huang Qi and Huang Qin with relevant cytochrome P 450 3A4 (CYP3A4) inhibition [3,4]. The effect and safety of temozolomide was not addressed in patients with severe hepatic impairment in clinical trials, but no dose adjustment is recommended in these patients according to manufacturer’s labeling.…”