Abstract
Context Cepharanthine (CEP) extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), has a range of therapeutic potential in clinical conditions. Whether it affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods The effects of CEP (100 μM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific probe actions and probe substrates. In addition, the enzyme kinetic parameters were calculated. Results The results showed that the activity of CYP3A4, CYP2E1 and CYP2C9 was inhibited by CEP, with IC50 values of 16.29, 25.62 and 24.57 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that CEP was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2C9, with Ki values of 8.12, 11.78 and 13.06 μM, respectively. Additionally, CEP is a time-dependent inhibitor for CYP3A4 with KI /Kinact value of 10.84/0.058 min/μM. Discussion and conclusions The in vitro studies of CEP with CYP isoforms indicate that CEP has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2C9. Further clinical studies are needed to evaluate the significance of this interaction.
Highlights
Cepharanthine (CEP) is a biscoclaurine alkaloid, extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), known to have anti-inflammatory and immunomodulatory activities (Fujii et al 1988)
Specific inhibitors of CYP1A2, CYP3A4, CYP2A6, CYP2E1, CYP2D6, CYP2C9, CYP2C19, and CYP2C8 were used as positive controls
The inhibitory kinetic data suggested that the inhibition of CYP3A4 was best fitted in a non-competitive manner (Figure 3(A)), and CYP2E1 (Figure 4(A)) and CYP2C9 (Figure 5(A)) was inhibited by CEP in a competitive manner
Summary
Cepharanthine (CEP) is a biscoclaurine alkaloid, extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), known to have anti-inflammatory and immunomodulatory activities (Fujii et al 1988). It has been reported that CEP has a range of therapeutic potential in clinical conditions (Shinobu and Jianghong 2007; Rogosnitzky and Danks 2011). Conditions that have been reported to benefit from CEP therapy including radiation-induced leukopoenia (Suzuki et al 1992), idiopathic thrombocytopenic purpura (Kobayashi et al 1992), alopecia areata and alopecia pityrodes (Nomoto et al 2004). CEP mitigates lung injury induced by bilateral lower limb I/R in rats (Kao et al 2015), and it might have a potential innovative antiplasmodial mechanism of action (Desgrouas et al 2014). With the development of the treatment of tumours, CEP has become more and more popular
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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
