Effects of catalpol on the activity of human liver cytochrome P450 enzymes

Liu, Lu; Cao, Xiangang; Li, Tingxin; Li, Xiaohua

doi:10.1080/00498254.2018.1558309

Cited by 9 publications

(4 citation statements)

References 37 publications

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“…Due to the complexity of components in the extract of herbs it is common that herb products exhibit different effects on the regulation of multiple enzymes. Sophora flavescens can inhibit CYP2B6, CYP2C8, CYP2C9, and CYP3A activities, while catalpol can inhibit the activity of CYP3A4, CYP2E1 and CYP2C9 19 , 20 . Other regulatory factors can also alter the expression of CYPs.…”

Section: Determinants Of Pkmentioning

confidence: 99%

Current trends in drug metabolism and pharmacokinetics

Meng

Yang

et al. 2019

Acta Pharmaceutica Sinica B

188

124

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Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug–drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

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Section: Determinants Of Pkmentioning

confidence: 99%

Current trends in drug metabolism and pharmacokinetics

Meng

Yang

et al. 2019

Acta Pharmaceutica Sinica B

188

124

View full text Add to dashboard Cite

show abstract

“…The interaction between CYP450s and various drugs has drawn special attention in the past decades. Numerous evidence has revealed a number of drugs that affected the activity of CYP450s and induced adverse interactions [13][14][15][16]. Obtusofolin is the main extraction of Catsia tora L., which has been widely applied in the ophthalmology prescription in the clinic [17].…”

Section: Discussionmentioning

confidence: 99%

In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1

Liu

Chen

et al. 2021

BMC Complement Med Ther

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Background Obtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin. Methods The effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 μM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver–Burk plots to characterize the specific inhibition model and kinetic parameters. Results Obtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 μM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 μM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 μM− 1 and the Kinact value of 0.0515 min− 1. Conclusions The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

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“…Diabetes also changes the experesion of cytochrome P450 enzymes, including CYP3A4, CYP2E1, CYP2C9, and CYP2D4 participate in phase I drug metabolism [33][34][35]. Catalpol has been shown to effect the activity of CYP3A4, CYP2E1 and CYP2C9 that resulted in pharmacokinetic interactions of coadministered drugs [36]. It is possible that differences in the pharmacokinetics of ZYD compounds in diabetic and normal rats may be caused by disease-associated changes in some functional enzymes.…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis and identification of the absorption and metabolic components of Zengye decoction in type 2 diabetic rats by HPLC-ESI-Q-TOF–MS/MS

et al. 2020

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Background Zengye decoction (ZYD) has been widely used in the treatment of type 2 diabetes mellitus (T2DM). Exploring the fate of various components of ZYD in vivo is of considerable significance for pharmacological research and molecular mechanism elaboration. However, the systematic analysis on the metabolic behavior of chemical components of ZYD in T2DM rats has not been reported. Methods To screen and characterize the complex chemical compositions of ZYD, and metabolism fate in plasma, urine, bile, and feces of T2DM rats, the model of T2DM rats was prepared. A rapid procedure using high-performance liquid chromatography coupled with electrospray ionization quadrupole time of flight tandem mass spectrometry (HPLC-ESI-Q-TOF–MS/MS) was established. Data were acquired and analyzed by Agilent MassHunter Workstation Qualitative Analysis software version B.07.00 and PCDL manager B.07.00. Results A total of 80 compounds were identified or tentatively characterized in ZYD, 31 more than previously detected. Besides, 36 prototype components and 49 metabolites of ZYD were found and characterized in T2DM rats, and the proposed fragmentation pathways and possible metabolic behaviors of the main types of compounds were described. Conclusions This study developed the understanding of the composition of ZYD as well as the cleavage rules and metabolic pathways of the prototype compounds. Besides, this study provided abundant data for further research and for study of the metabolism of traditional Chinese medicine prescriptions.

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Effects of catalpol on the activity of human liver cytochrome P450 enzymes

Cited by 9 publications

References 37 publications

Current trends in drug metabolism and pharmacokinetics

Current trends in drug metabolism and pharmacokinetics

In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1

Systematic analysis and identification of the absorption and metabolic components of Zengye decoction in type 2 diabetic rats by HPLC-ESI-Q-TOF–MS/MS

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