<i>In vitro</i> inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes

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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“… 2018 ; Wu, Li, et al. 2020 ; Yu et al. 2020 ), and its antitumor effect was observed in breast cancer and other malignant tumours (Wang et al.…”

Section: Discussionmentioning

confidence: 99%

“…For example, lysionotin that is extracted from Lysionotus pauciflorus Maxim (Gesneriaceae) was revealed to inhibit the activity of CYP2C8, 2C19, and 3A4 in a dose-dependent manner (Li et al. 2020 ). Terminalia chebula Retz.…”

Section: Discussionmentioning

confidence: 99%

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

Song

Wei

Yang

et al. 2022

Pharmaceutical Biology

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“… 2020 ; Li et al. 2020 ). The activity of CYP3A4 was evaluated by the concentration of substrates with the employment of HPLC.…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the inhibition of CYP3A4 enzyme activity, the interaction was performed with rat liver microsomes, typical CYP3A4 substrates (testosterone), and various concentrations of baicalein, according to the previous study (Ding et al 2020;Li et al 2020). The activity of CYP3A4 was evaluated by the concentration of substrates with the employment of HPLC.…”

Section: Cyp3a4 Inhibition Assaymentioning

confidence: 99%

Baicalein inhibits the pharmacokinetics of simvastatin in rats via regulating the activity of CYP3A4

Meng

Zhang

et al. 2021

Pharmaceutical Biology

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Context: Baicalein and simvastatin possess similar pharmacological activities and indications. The risk of their co-administration was unclear. Objective: The interaction between baicalein and simvastatin was investigated to provide reference and guidance for the clinical application of the combination of these two drugs. Materials and methods: The pharmacokinetics of simvastatin was investigated in Sprague-Dawley rats (n ¼ 6). The rats were pre-treated with 20 mg/kg baicalein for 10 days and then administrated with 40 mg/ kg simvastatin. The single administration of simvastatin was set as the control group. The rat liver microsomes were employed to assess the metabolic stability and the effect of baicalein on the activity of CYP3A4. Results: Baicalein significantly increased the AUC (0-t) (2018.58 ± 483.11 vs. 653.05 ± 160.10 lg/L Â h) and C max (173.69 ± 35.49 vs. 85.63 ± 13.28 lg/L) of simvastatin. The t 1/2 of simvastatin was prolonged by baicalein in vivo and in vitro. The metabolic stability of simvastatin was also improved by the co-administration of baicalein. Baicalein showed an inhibitory effect on the activity of CYP3A4 with the IC 50 value of 12.03 lM, which is responsible for the metabolism of simvastatin. Discussion and conclusion: The co-administration of baicalein and simvastatin may induce drug-drug interaction through inhibiting CYP3A4. The dose of baicalein and simvastatin should be adjusted when they are co-administrated.

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“…Three groups were set as the untreated group (negative control), treated with 100 µM dendrobine (dendrobine group), or treated with corresponding inhibitors at cer-tain concentrations (positive control) (▶ Table 1). The specific substrates, corresponding marker reactions, and reaction conditions are summarized in ▶ Table 1 according to previous studies [10,26,27]. The corresponding substrates were obtained from Sigma Chemical Co. and the purity was over 98 %.…”

Section: Effect Of Dendrobine On the Activity Of Cytochrome P450 Enzymesmentioning

confidence: 99%

In Vitro Investigation on the Effect of Dendrobine on the Activity of Cytochrome P450 Enzymes

et al. 2022

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Dendrobine is the major active ingredient of Dendrobium nobile, Dendrobium chrysotoxum, and Dendrobium fimbriatum, all of which are used in traditional Chinese medicine owing to their antitumor and anti-inflammation activities. Hence, investigation on the interaction of dendrobine with cytochrome P450 enzymes could provide a reference for the clinical application of Dendrobium. The effects of dendrobine on cytochrome P450 enzymes activities were investigated in the presence of 0, 2.5, 5, 10, 25, 50, and 100 µM dendrobine in pooled human liver microsomes. The specific inhibitors were employed as the positive control and the blank groups were set as the negative control. The Lineweaver-Burk plots were plotted to characterize the specific inhibition model and obtain the kinetic parameters. The study reveals that dendrobine significantly inhibited the activity of CYP3A4, 2C19, and 2D6 with IC50 values of 12.72, 10.84, and 15.47 µM, respectively. Moreover, the inhibition of CYP3A4 was found to be noncompetitive (Ki = 6.41 µM) and time dependent (KI = 2.541 µM−1, Kinact = 0.0452 min−1), while the inhibition of CYP2C19 and 2D6 was found to be competitive with the Ki values of 5.22 and 7.78 µM, respectively, and showed no time-dependent trends. The in vitro inhibitory effect of dendrobine implies the potential drug-drug interaction between dendrobine and CYP3A4-, 2C9-, and 2D6-metabolized drugs. Nonetheless, these findings need further in vivo validation.

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In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes

Cited by 12 publications

References 31 publications

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

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

Baicalein inhibits the pharmacokinetics of simvastatin in rats via regulating the activity of CYP3A4

In Vitro Investigation on the Effect of Dendrobine on the Activity of Cytochrome P450 Enzymes

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