Herb-drug interaction of 50 Chinese herbal medicines on CYP3A4 activity in vitro and in vivo.
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.
School of Pharmacy, National Defense Medical Center, 161 MinchuanEast Road Section 6, Taipei, Taiwan. paolh@ndmctsgh.edu.tw
Li-Heng
LH
Pao
Oliver Yoa-Pu
OY
Hu
Hsien-Yuan
HY
Fan
Chang-Ching
CC
Lin
Liang-Chun
LC
Liu
Pei-Wei
PW
Huang
D000818:Animals; D027883:Astragalus Plant; D027885:Astragalus propinquus; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007887:Fabaceae; D041743:Herb-Drug Interactions; D006801:Humans; D031566:Magnolia; D019684:Magnoliopsida; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D029596:Paeonia; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C499814:Scutellaria baicalensis extract; C027492:Huang Qi; D051544:Cytochrome P-450 CYP3A