scholarly journals Selective Inhibition of Bakuchicin Isolated fromPsoralea corylifoliaon CYP1A in Human Liver Microsomes

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Sun Joo Kim ◽  
Heung Chan Oh ◽  
Youn-Chul Kim ◽  
Gil-Saeng Jeong ◽  
Sangkyu Lee
Keyword(s):  
Human Liver ◽  
Competitive Inhibition ◽  
Biological Activities ◽  
Biological Effects ◽  
Liver Microsomes ◽  
Selective Inhibition ◽  
Human Liver Microsomes ◽  
Inhibition Mechanism ◽  
Inhibitory Effects ◽  
Cyp Isoforms

Bakuchicin is a furanocoumarin isolated fromPsoralea corylifoliaand shows several biological activities. Although there have been studies on the biological effects of bakuchicin, its modulation potency of CYP activities has not been previously investigated. Here, we investigated the inhibitory effects of bakuchicin on the activities of CYP isoforms by using a cocktail of probe substrates in pooled human liver microsomes (HLMs) and human recombinantcDNA-expressedCYP. Bakuchicin strongly inhibited CYP1A-mediated phenacetinO-deethylation with an IC50value of 0.43 μM in HLMs. It was confirmed by human recombinantcDNA-expressedCYP1A1 and CYP1A2 with aKivalue of 0.11 μM and 0.32 μM, respectively. A Lineweaver-Burk plot indicated that the inhibition mechanism of bakuchicin was competitive inhibition. Overall, this is the first study to investigate the potential CYP1A1 and CYP1A2 inhibition associated with bakuchicin and to report its competitive inhibitory effects on HLMs.

scholarly journals Inhibitory Effects of Baicalein Derived from Japanese Traditional Herbal Medicine on SN-38 Glucuronidation

2018 ◽  
Vol 21 ◽  
pp. 195-206 ◽  
Author(s):  
Takashi Satoh ◽  
Ayaka Igarashi ◽  
Misaki Tanno ◽  
Koki Yamada ◽  
Natsuko Takahashi-Suzuki ◽  
...  
Keyword(s):  
Human Liver ◽  
Competitive Inhibition ◽  
Active Form ◽  
Liver Microsomes ◽  
Herbal Medicines ◽  
Initial Reaction Rate ◽  
Human Liver Microsomes ◽  
Initial Reaction ◽  
Pharmacokinetic Studies ◽  
Inhibitory Effects

Purpose: The chemotherapeutic agent irinotecan is hydrolyzed to its active form SN-38 by human carboxyesterases, but SN-38 is converted into the inactive form SN-38G by hepatic UDP-glucuronosyltransferases (UGTs). The aim of the present study was to evaluate the inhibitory effects of two b-glucuronidase-treated Japanese traditional herbal medicines (kampo), Hange-Shashin-To (TJ-14) and Sairei-To (TJ-114) on SN-38 glucuronidation, and the deglycosylation of baicalin (BG) and glycyrrhizic acid (GL) derived from TJ-14 and TJ-114 to form their respective aglycones, baicalein (BA) and glycyrrhetinic acid (GA). Methods: The inhibitory effects of b-glucuronidase-treated TJ-14 and TJ-114 on SN-38 glucuronidation by human liver microsomes were examined. BA and GA, which were enzymatically converted from BG and GL present in TJ-14 and TJ-114, were examined in the same manner. Furthermore, the enzymatic activities were measured by using recombinant UGT1A1 and UGT1A9 isoforms instead of human liver microsomes. BA, GA, SN-38, and their glycosides/glucuronides were analyzed with an LC-MS system. Results: As regards the linear initial reaction rate, SN-38 glucuronidation by human liver microsomes was significantly inhibited by the addition of b-glucuronidase-untreated TJ-14 and TJ-114, but was more strongly inhibited by the addition of b-glucuronidase-treated TJ-14 and TJ-114. The results of LC-MS analysis and pharmacokinetic studies suggested that BA is the main inhibitor of SN-38 glucuronidation. In the Dixon plot, BA showed competitive inhibition of SN-38 glucuronidation, and the inhibition constant was 8.70 ± 3.24 mM. Previous reports, studies of recombinant UGT isoforms indicated that SN-38 glucuronidation was mainly catalyzed by UGT1A1. Conclusions: These findings strongly suggested that SN-38 glucuronidation is inhibited by BA. BA could act as a pharmacokinetic regulating factor associated with SN-38 glucuronidation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Selective Inhibition of Cytochrome P450 2D6 by Sarpogrelate and Its Active Metabolite, M-1, in Human Liver Microsomes

2013 ◽  
Vol 42 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Doo-Yeoun Cho ◽  
Soo Hyeon Bae ◽  
Joeng Kee Lee ◽  
Yang Weon Kim ◽  
Bom-Taeck Kim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Metabolite ◽  
Human Liver ◽  
Liver Microsomes ◽  
Selective Inhibition ◽  
Human Liver Microsomes ◽  
Cytochrome P450 2D6 ◽  
P450 2D6

scholarly journals Erratum: In Vitro Metabolism and Inhibitory Effects of Pranlukast in Human Liver Microsomes [Biol. Pharm. Bull. 32(4): 688-693 (2009)]

2009 ◽  
Vol 32 (7) ◽  
pp. 1311
Author(s):  
Kazuhiro Yoneda ◽  
Ichiro Matsumoto ◽  
Fumitaka Sutoh ◽  
Ryunosuke Higashi ◽  
Ken-ichi Nunoya ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
In Vitro Metabolism ◽  
Inhibitory Effects

Inhibitory Effects of Calf Thymus DNA on Metabolism Activity of CYP450 Enzyme in Human Liver Microsomes

2014 ◽  
Vol 29 (6) ◽  
pp. 475-481 ◽  
Author(s):  
Shuoye Yang ◽  
Zhixia Qiu ◽  
Qiuyang Zhang ◽  
Jiayin Chen ◽  
Xijing Chen
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Calf Thymus Dna ◽  
Inhibitory Effects ◽  
Calf Thymus ◽  
Cyp450 Enzyme

scholarly journals Inhibition of Cytochrome P450 Activities by Sophora flavescens Extract and Its Prenylated Flavonoids in Human Liver Microsomes

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Daeun Yim ◽  
Min Jung Kim ◽  
Yumi Shin ◽  
Su-Jun Lee ◽  
Jae Gook Shin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
East Asian ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Pharmacological Properties ◽  
Asian Countries ◽  
Sophora Flavescens ◽  
Prenylated Flavonoids ◽  
Cyp Isoforms

Sophora flavescens possesses several pharmacological properties and has been widely used for the treatment of diarrhea, inflammation, abscess, dysentery, and fever in East Asian countries. S. flavescens is a major source of prenylated flavonoids, such as sophoraflavone and kushenol. In this study, we examined the effects of S. flavescens extract and its prenylated flavonoids on cytochrome P450 (CYP) isoform activity in human liver microsomes. The extract inhibited CYP2C8, CYP2C9, CYP2C19, and CYP3A activities, with IC50 values of 1.42, 13.6, 19.1, and 50 µg/mL, respectively. CYP2B6 was only inhibited in human liver microsomes preincubated with the extract. CYP3A4 was more strongly inhibited by the extract in the presence of NADPH, suggesting that the extract may inhibit CYP2B6 and CYP3A4 via mechanism-based inactivation. Prenylated flavonoids also inhibited CYP isoforms with different selectivity and modes of action. Kushenol I, leachianone A, and sophoraflavone G inhibited CYP2B6, whereas kushenol C, kushenol I, kushenol M, leachianone A, and sophoraflavone G inhibited CYP3A4 via mechanism-based inhibition. Our results suggest that S. flavescens may contribute to herb–drug interactions when coadministered with drugs metabolized by CYP2B6, CYP2C8, CYP2C9, and CYP3A4.

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