In vitro and in vivo assessment of cytochrome P450-mediated herb-drug interaction of Ssang-hwa-tang

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• 作者：Sang Yoon Lee^a ; Ji-Yoon Lee^a ; Wonku Kang^b ; Kwang-il Kwon^a ; Soo Jin Oh^c ; Jin Yeul Ma^d ; ^{jyma@kiom.re.kr} ; Sang Kyum Kim^a ; ^{sangkim@cnu.ac.kr}
• 关键词：Cytochrome P450 ; Fermentation ; Herb&ndash ; drug interaction ; Ssang-hwa-tang
• 刊名：Food Chemistry
• 出版年：2013
• 出版时间：15 January, 2013
• 年：2013
• 卷：136
• 期：2
• 页码：450-457
• 全文大小：452 K

文摘

We have evaluated the herb-drug interaction potential of Ssang-hwa-tang (SHT) mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated herb-drug interaction potential were determined. SHT showed inhibitory activity toward CYP1A2, but not 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes. The results of the enzyme kinetic study suggested that the SHT-induced CYP1A2 inhibition is mixed reversible inhibition. The hepatic CYP expression and activity in rats treated with SHT were examined. The expression/activity of CYP2E1 increased as a result of SHT extract treatment (P < 0.005 or P < 0.001, respectively), which raises the possibility that SHT may increase the toxicity of environmental toxicants through the elevation of CYP2E1-mediated metabolic activation. SHT fermentation using Lactobacillus fermentum or Lactobacillus gasseri resulted in attenuation of the SHT-induced CYP1A2 inhibition, but not CYP2E1 induction, suggesting that changes in the chemical composition of SHT through fermentation can affect the inhibition of CYP1A2 activity.