<i>In vitro</i> inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes

Zhang, Xunge; Feng, Ping; Gao, Xinfu; Wang, Bin; Gou, Chunxia; Bian, Ruimin

doi:10.1080/13880209.2020.1741650

Cited by 11 publications

(12 citation statements)

References 34 publications

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“…The effect of pogostone on the activity of CYP450s was investigated with probe reactions (summarized in Table 1) in HLMs in accordance with previous studies (Zhang et al 2007(Zhang et al , 2020. All incubations were conducted in triplicate with a volume of 200 lL, containing 100 mM potassium phosphate buffer (pH 7.4), NADPH-generating system (1 mM NADP þ , 10 mM glucose-6phosphate, 1 U/mL of glucose-6-phosphate dehydrogenase, and 4 mM MgCl 2 ), corresponding probe substrates, HLM, and 100 lM pogostone or positive inhibitors.…”

Section: Assay With Hlmsmentioning

confidence: 81%

“…A variety of drugs have been reported to inhibit or induce the activity of CYP450s, such as dihydromyricetin (Liu et al 2017), cepharanthine (Zhang et al 2020), and paroxetine (Kamel and Lamsabhi 2020). Here, the effects of pogostone on the activity of CYP1A2, 2A6, 2A4, 2C8, 2C9, 2C19, 2D6, and 2E1 were investigated in vitro in pooled human liver microsomes.…”

Section: Introductionmentioning

confidence: 99%

“… 2017 ), cepharanthine (Zhang et al. 2020 ), and paroxetine (Kamel and Lamsabhi 2020 ). Here, the effects of pogostone on the activity of CYP1A2, 2A6, 2A4, 2C8, 2C9, 2C19, 2D6, and 2E1 were investigated in vitro in pooled human liver microsomes.…”

Section: Introductionmentioning

confidence: 99%

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Pogostone inhibits the activity of CYP3A4, 2C9, and 2E1 in vitro

Zhang

et al. 2021

Pharmaceutical Biology

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Context: Pogostone possesses various pharmacological activities, which makes it widely used in the clinic. Its effect on the activity of cytochrome P450 enzymes (CYP450s) could guide its clinical combination. Objective: To investigate the effect of pogostone on the activity of human CYP450s. Materials and methods: The effect of pogostone on the activity of CYP450s was evaluated in human liver microsomes (HLMs) compared with blank HLMs (negative control) and specific inhibitors (positive control). The corresponding parameters were obtained with 0-100 lM pogostone and various concentrations of substrates.Results: Pogostone was found to inhibit the activity of CYP3A4, 2C9, and 2E1 with the IC 50 values of 11.41, 12.11, and 14.90 lM, respectively. The inhibition of CYP3A4 by pogostone was revealed to be performed in a non-competitive and time-dependent manner with the K i value of 5.69 lM and the KI/K inact value of 5.86/0.056/(lM/min). For the inhibition of CYP2C9 and 2E1, pogostone acted as a competitive inhibitor with the K i value of 6.46 and 7.67 lM and was not affected by the incubation time. Discussion and conclusions: The inhibitory effect of pogostone on the activity of CYP3A4, 2C9, and 2E1 has been disclosed in this study, implying the potential risk during the co-administration of pogostone and drugs metabolized by these CYP450s. The study design provides a reference for further in vivo investigations to validate the potential interaction.

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Section: Assay With Hlmsmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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Pogostone inhibits the activity of CYP3A4, 2C9, and 2E1 in vitro

Zhang

et al. 2021

Pharmaceutical Biology

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“… 2019 ; Zhang, Feng, et al. 2020 ). The incubation system also included alpinetin ( Figure 1 , 99%, Chengdu Munster Biothechnology Co, China, or specific inhibitors) and an β-NADPH generating system as previously reported in the potassium phosphate buffer with a final volume of 200 μL.…”

Section: Methodsmentioning

confidence: 99%

Alpinetin suppresses CYP3A4, 2C9, and 2E1 activity in vitro

Song

Wei

Yang

et al. 2022

Pharmaceutical Biology

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Context Alpinetin, the major active constitutes of Alpinia katsumata Hayata (Zingiberaceae), has been demonstrated to possess the activity of anti-breast cancer. Cytochrome P450 enzymes (CYP450s) plays vital roles in the biotransformation of various drugs. Objective To assess the effect of alpinetin on the activity of CYP450s and estimate the inhibition characteristics. Materials and methods The activity of CYP450s was evaluated in pooled human liver microsomes with corresponding substrates and marker reactions. The effect of alpinetin was compared with blank control (negative control) and corresponding inhibitors (positive control). The dose-dependent and time-dependent experiments were conducted in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM alpinetin and incubated for 0, 5, 10, 15, and 30 min. Results Alpinetin suppressed CYP3A4, 2C9, and 2E1 activity. All the inhibitions were significantly influenced by alpinetin contration with the IC 50 values of 8.23 μM (CYP3A4), 12.64 μM (CYP2C9), and 10.97 μM (CYP2E1), respectively. The inhibition of CYP3A4 was fitted with the non-competitive model with a Ki value of 4.09 μM and was time-dependent with KI and Kinact values of 4.67 min and 0.041 μM −1 , respectively. While CYP2C9 and 2E1 were inhibited by alpinetin competitively with Ki values of 6.42 (CYP2C9) and 5.40 μM (CYP2E1), respectively, in a time-independent manner. Discussion and conclusion The in vitro inhibitory effect of alpineticn on CYP3A, 2C9, and 2E1 implied the potential interaction of alpinetin or its origin herbs with the drugs metabolised by those CYP450s, which needs further in vivo validation.

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“…Using these parameters, the Ki values of the substances were calculated with the following formula [26]:…”

Section: Kinetic Studiesmentioning

confidence: 99%