scholarly journals Inhibitory Effect of Lygodium Root on the Cytochrome P450 3A Enzyme in vitro and in vivo

2020 ◽  
Vol Volume 14 ◽  
pp. 1909-1919
Author(s):  
Yunfang Zhou ◽  
Ailian Hua ◽  
Quan Zhou ◽  
Peiwu Geng ◽  
Feifei Chen ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Inhibitory Effect ◽  
Cytochrome P450 3A

In vitro inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6

2021 ◽  
Vol 36 (4) ◽  
pp. 259-270
Author(s):  
Boon Hooi Tan ◽  
Nafees Ahemad ◽  
Yan Pan ◽  
Uma Devi Palanisamy ◽  
Iekhsan Othman ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
High Performance ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Time Curve ◽  
Clinical Drugs ◽  
Inhibition Potencies ◽  
P450 2D6

Abstract Objectives Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug–natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6. Methods CYP2D6 was heterologously expressed in Escherichia coli. CYP2D6–antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking. Results The high-performance liquid chromatography (HPLC)-based dextromethorphan O-demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC50 values >300 µM). Diacerein exhibited moderate inhibition with IC50 and K i values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC50=26.22 μM and K i =32.27 μM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro–in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition. Conclusions Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

Does Crizotinib Auto-Inhibit CYP3A in vivo?

Pharmacology ◽  
2020 ◽  
Vol 105 (11-12) ◽  
pp. 715-718
Author(s):  
Abigail R. Bland ◽  
Nensi Shrestha ◽  
Rhonda J. Rosengren ◽  
John C. Ashton
Keyword(s):  
Lung Cancer ◽  
Cytochrome P450 ◽  
Western Blot ◽  
Anaplastic Lymphoma Kinase ◽  
Kinase Inhibitor ◽  
Cyp3a Activity ◽  
Cytochrome P450 3A ◽  
Anaplastic Lymphoma

Crizotinib is a tyrosine kinase inhibitor used to treat anaplastic lymphoma kinase-positive lung cancer. There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics. In order to test whether crizotinib treatment alters CYP3A activity in vivo, mice were treated with 5 and 25 mg/kg crizotinib (p.o.) daily for 14 days. Results showed that crizotinib treatment did not alter CYP3A activity as determined by erythromycin <i>N</i>-demethylation. In addition, CYP3A polypeptide expression as measured by Western blot was unchanged. Therefore, our results do not support CYP3A inhibition by crizotinib in vivo.

scholarly journals In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol

2011 ◽  
Vol 4 (2) ◽  
pp. 78-84 ◽  
Author(s):  
Galia Zamaratskaia ◽  
Martin Rasmussen ◽  
Isabelle Herbin ◽  
Bo Ekstrand ◽  
Vladimir Zlabek
Keyword(s):  
Cytochrome P450 ◽  
Inhibitory Effect ◽  
17Β Estradiol ◽  
Cyp2e1 Activity ◽  
High Concentrations ◽  
Testicular Steroids ◽  
Sexually Mature

In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol Sexually mature pigs are known to possess high concentrations of testicular steroids, which have been shown to change the activities of cytochrome P450 in vitro. The aim of the present study was to evaluate the regulation of CYP1A and CYP2E1 activity by the steroids dihydrotestosterone (DHT), 3β-androstenol, 17β-estradiol and 17α-estradiol. Catalytic activities of 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) were used as markers of CYP1A activities, while p-nitrophenol hydroxylase (PNPH) was used as a marker of CYP2E1 activities. Of the steroids tested, only 17β-estradiol and 17α-estradiol inhibited EROD and MROD activities. This inhibition was observed when a steroid concentration of 100 μM was used, while lower concentrations showed no inhibitory effect. PNPH activities were inhibited only by 100 μM of 17β-estradiol. The significance of these results in vivo is unknown because inhibition was only found when concentrations of estrogens higher than physiological levels were used. Nevertheless, the results provided further evidence on the important role of estrogens in regulation of porcine cytochrome P450 activities.

scholarly journals In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melegueta and Denniettia tripetala extracts

2017 ◽  
Vol 10 (6) ◽  
pp. 576-581 ◽  
Author(s):  
Sunday O. Nduka ◽  
Mathew J. Okonta ◽  
Daniel L. Ajaghaku ◽  
Chinwe V. Ukwe
Keyword(s):  
Cytochrome P450 ◽  
Enzyme Inhibition ◽  
Cytochrome P450 3A

Developmental Changes in the Expression and Function of Cytochrome P450 3A Isoforms: Evidence from In Vitro and In Vivo Investigations

2013 ◽  
Vol 52 (5) ◽  
pp. 333-345 ◽  
Author(s):  
Ibrahim Ince ◽  
Catherijne A. J. Knibbe ◽  
Meindert Danhof ◽  
Saskia N. de Wildt
Keyword(s):  
Cytochrome P450 ◽  
Developmental Changes ◽  
Cytochrome P450 3A ◽  
And Function

In vitro inhibitory effect of West African medicinal and food plants on human cytochrome P450 3A subfamily

2010 ◽  
Vol 128 (2) ◽  
pp. 390-394 ◽  
Author(s):  
Amegnona Agbonon ◽  
Kwashie Eklu-Gadegbeku ◽  
Kodjo Aklikokou ◽  
Messanvi Gbeassor ◽  
Koffi Akpagana ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Inhibitory Effect ◽  
West African ◽  
Food Plants ◽  
Cytochrome P450 3A ◽  
Human Cytochrome

In vitro and in vivo Inhibitory Effects of Glycyrrhetinic Acid on Cytochrome P450 3A Activity

Pharmacology ◽  
2010 ◽  
Vol 86 (5-6) ◽  
pp. 287-292 ◽  
Author(s):  
Hai Yun Li ◽  
Wen Xu ◽  
Juan Su ◽  
Xi Zhang ◽  
Li Wei Hu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Glycyrrhetinic Acid ◽  
Cytochrome P450 3A ◽  
Inhibitory Effects

Nonionic surfactants are strong inhibitors of cytochrome P450 3A biotransformation activity in vitro and in vivo

2009 ◽  
Vol 36 (4-5) ◽  
pp. 401-411 ◽  
Author(s):  
Xiuhua Ren ◽  
Xinliang Mao ◽  
Lei Cao ◽  
Kewen Xue ◽  
Luqin Si ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Nonionic Surfactants ◽  
Cytochrome P450 3A
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