In vitro inhibitory effect of piperlonguminine isolated from Piper longum on human cytochrome P450 1A2

Song, Min; Hwang, Jae Yun; Lee, Min Young; Jee, Jun-Goo; Lee, You Mie; Bae, Jong-Sup; Kim, Jeong Ah; Lee, Seung Ho; Lee, Sangkyu

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자료유형: 학술저널

저자정보: Song, Min (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Hwang, Jae Yun (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Lee, Min Young (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Jee, Jun-Goo (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Lee, You Mie (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Bae, Jong-Sup (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Kim, Jeong Ah (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) Lee, Seung Ho (College of Pharmacy, Yeungnam University) Lee, Sangkyu (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)

저널정보: 대한약학회 Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 제37권 제8호

발행연도: 2014.1

수록면: 1,063 - 1,068 (6page)

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Piperlonguminine (PL), a major alkaloid isolated from Piper longum fruits, shows several biological activities including anti-tumor, anti-hyperlipidemic and anti-inflammatory effects. Although there have been studies of the biological effects of PL, the potential drug-interaction effect of PL following evaluation of inhibitory effects of cytochrome P450 (CYP) activities was not investigated. Here, to investigate the inhibitory effects of PL on the activities of CYP isoforms, CYP inhibition assays were conducted using a cocktail of probe substrates in pooled human liver microsome (HLMs) and human recombinant cDNA-expressed CYP. PL strongly inhibited CYP1A2-mediated phenacetin O-deethylation with an $IC_{50}$ value of $8.8{\mu}M$, as NADPH-independent inhibition, while other CYPs were not significantly inhibited. A Lineweaver-Burk plot resulted in the inhibition mechanism of PL being divided into two different modes, reversible competitive inhibition in a low concentration range of $0-16{\mu}M$ with a $K_i$ value of $1.39{\mu}M$ and uncompetitive inhibitory behavior at a high concentration range of $16-40{\mu}M$. In addition, PL only decreased CYP 1A2-catalyzed phenacetin O-deethylase activity with $IC_{50}$ values of $10.0{\mu}M$ in human recombinant cDNA-expressed 1A2, not 1A1. Overall, this is the first investigation of potential herb-drug interactions associated with PL conducted by identifying the competitive inhibitory effects of PL on CYP1A2 in HLMs.

#Piperlonguminine #CYP1A2 #Human liver microsomes #Herb-drug interaction #Competitive inhibition

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