Abstract
Context: Bergenin, isolated from the herb of Bergenia purpurascens (Hook. f. et Thoms.) Engl., has anti-inflammatory, antitussive, and wound healing activities. However, whether bergenin affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear.Materials and methods: In this study, the inhibitory effects of bergenin (100 μM) on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated, enzyme kinetics and time-dependent inhibition studies were also performed in vitro using human liver microsomes (HLMs).Results: The results showed that bergenin inhibited the activity of CYP3A4, 2E1 and 2C9, with IC50 values of 14.39, 22.83 and 15.11 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that bergenin was not only a non-competitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1 and 2C9, with Ki values of 7.71, 11.39 and 8.89 μM, respectively. In addition, bergenin is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.025/3.50 μM−1 min−1.Discussion and conclusions: The in vitro studies of bergenin with CYP isoforms indicate that bergenin has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, 2E1 and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.
Highlights
Bergenia purpurascens (Hook. f. et Thoms.) Engl., a traditional Chinese medicine, possesses anti-inflammation and antidiarrhoeal abilities and is used clinically for the treatment of diarrhoea, dysentery and other gut-associated diseases (Shi et al 2014; Pandey et al 2017; Liu et al 2018)
To investigate whether the bergenin affects the catalytic activity of cytochrome P450 (CYP) enzymes, the probe reaction assays were conducted with varying concentrations of bergenin (Figure 1)
Lineweaver–Burk plots of inhibitory kinetic data suggested that the inhibition of the inhibition of CYP3A4 by bergenin was best fit in a non-competitive manner (Figure 3(A)), whereas CYP2E1 (Figure 4(A)) and 2C9 (Figure 5(A)) by bergenin was the best fit in a competitive manner
Summary
Bergenia purpurascens (Hook. f. et Thoms.) Engl., a traditional Chinese medicine, possesses anti-inflammation and antidiarrhoeal abilities and is used clinically for the treatment of diarrhoea, dysentery and other gut-associated diseases (Shi et al 2014; Pandey et al 2017; Liu et al 2018). Bergenin is the major bioactive ingredient in the herb–drug (Li et al 2013; Pandey et al 2017). It is used as an antiarrhythmic, antifungal, anticancer, antidiabetic and antioxidant agent (Bessong et al 2005; Ahmed and Urooj 2012; Bajracharya 2015; Aggarwal et al 2016). Many adverse herb–drug interactions may be attributed to the inhibition of CYP450 enzymes by co-administrated drugs or herbs (Zhang et al 2007; Nowack 2008; Jeong et al 2013; Lee et al 2013; Qi et al 2013; Meng and Liu 2014). To the best of our knowledge, few studies have investigated the effects of bergenin on CYP enzymes, the inhibitory effects, which will increase the risk of therapeutic applications of bergenin and its medical preparations
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
