Abstract
BackgroundDiazepam is a benzodiazepine drug used to treat anxiety, insomnia, and muscle spasms. Imperatorin is a phytochemical isolated from medicinal plants and is widely used in herbal medicine. The aim of this study was to investigate the interactions between imperatorin and diazepam in vitro and in vivo and to provide evidence-based guidance for the safe clinical use of the drug.MethodsIn vitro inhibition of imperatorin was assessed by incubating rat liver microsomes with diazepam to determine IC50 values and the type of inhibition. For in vivo assessment, six rats were pretreated with 50 mg/kg imperatorin for two weeks, six were administered saline, and a single dose of 10 mg/kg diazepam was administered orally to both groups 30 min after the administration of imperatorin.ResultsImperatorin inhibited the in vitro metabolism of diazepam via the competitive mechanism of CYP450. The IC50 values of imperatorin to nordazepam and temazepam were 1.54 μM and 1.80 μM, respectively. The inhibitory constant values for temazepam and nordazepam were 1.24 μM and 1.29 μM, respectively. Long-term administration of imperatorin significantly increased the AUC(0-12h), AUC(0-∞), and Cmax of diazepam, while Vz/F and CLz/F were decreased significantly (P < 0.05). In turn, the AUC(0-12h), AUC(0-∞), and Cmax of nordazepam and temazepam decreased significantly, and Vz/F and CLz/F increased significantly (P < 0.05).ConclusionsThis study demonstrates that imperatorin inhibits the metabolism of diazepam both in vitro and in vivo. These results indicated that more attention should be paid when taking diazepam together with food or herbs containing IMP, although further investigation is still needed.
Highlights
Imperatorin (IMP), a linear furocoumarin compound, is widely found in the roots of the medicinal plants Cynanchum otophyllum Schneid, Angelica sinensis, and Angelica dahurica (Garcıá -Argμez et al, 2000; Zhang et al, 2010; Badziul et al, 2014; Morris et al, 2018)
Elution was performed in a linear gradient where the acetonitrile content increased from 10% to 30% within 0.3 min and continued to increase from 30% to 95% between 0.3 and 2.0 min
Various concentrations of IMP ranging from 0.1 mM to 100 mM were used to determine the IC50 values of diazepam metabolism to temazepam and nordiazepam (Figure 3), which were found to be 1.80 mM and1.54 mM, respectively
Summary
Imperatorin (IMP), a linear furocoumarin compound, is widely found in the roots of the medicinal plants Cynanchum otophyllum Schneid, Angelica sinensis, and Angelica dahurica (Garcıá -Argμez et al, 2000; Zhang et al, 2010; Badziul et al, 2014; Morris et al, 2018). IMP has good antibacterial activity and different degrees of inhibition on Escherichia coli, degenerative bacteria, Staphylococcus aureus, and Salmonella typhimurium (Tsassi et al, 2010). It can inhibit the infection of T cells and HeLa cells by human immunodeficiency virus type 1 (HIV-1), vesicular stomatitis virus pseudotype, and glycoprotein gp160-enveloped (Sancho et al, 2004). The aim of this study was to investigate the interactions between imperatorin and diazepam in vitro and in vivo and to provide evidence-based guidance for the safe clinical use of the drug
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
