In vitro inhibitory effects of dihydromyricetin on human liver cytochrome P450 enzymes

Abstract

Context: Dihydromyricetin (DHM) is the most abundant and active flavonoid component isolated from Ampelopsis grossedentata (Hand-Mazz) W.T. Wang (Vitaceae) and it possesses numerous pharmacological activities. However, whether DHM affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods: The inhibitory effects of DHM 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). Results:The results showed that DHM could inhibit the activity of CYP3A4, CYP2E1 and CYP2D6, with IC 50 values of 14.75, 25.74 and 22.69 lM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that DHM was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2D6, with Ki values of 6.06, 9.24 and 10.52 lM, respectively. In addition, DHM is a time-dependent inhibitor for CYP3A4 with K I /K inact value of 12.17/0.057 min À1 lM À1 . Discussion and conclusion: The in vitro studies of DHM with CYP isoforms indicate that DHM has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2D6. Further clinical studies are needed to evaluate the significance of this interaction. ARTICLE HISTORY

In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes

“…As previous studies reported, CYP2E1 and CYP2C9 play a vital role in the metabolism of many drugs (He et al 2009;Lim et al 2014;Xu et al 2017;Bedada and Neerati 2018). There are also many drugs inhibiting the activity of CYP2E1 and CYP2C9 (Pan et al 2010;Jiang et al 2016;Liu et al 2017;Hao et al 2018), and we get similar results in the study of CEP. Different from CYP3A4, the activity of human liver microsomal CYP2E1 and CYP2C9 was inhibited by CEP competitively.…”

“…The induction or inhibition of CYPs is a major mechanism that underlies drug-drug interactions (Manikandan and Nagini 2018). For example, dihydromyricetin, berberine and pristimerin have inhibitory effects on the activity of CYPs (Chang et al 2015;Liu et al 2017;Hao et al 2018). Glycyrrhizic acid, verapamil and grapefruit juice may affect the pharmacokinetics of other drugs through inhibiting CYPs (Huang et al 2018;Jia et al 2018;Zhao et al 2018).…”

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

“…It is necessary to investigate the effect of different drugs or herbs on the activity of CYPs, which would provide more reference for the clinical usage or co-administration of drugs. Dihydromyricetin, berberine, and pristimerin have inhibitory effects on the activity of CYPs (Chang et al 2015;Liu et al 2017;Hao et al 2018). However, whether lysionotin could affect the activity of CYPs is still unclear.…”

Nitidine Chloride Is a Mechanism-Based Inactivator of CYP2D6

“…DC (Liangmianzhen in Chinese), a classic traditional Chinese medicinal (TCM) plant distributed mainly in northeastern Asia (Liao et al, 2013;. The roots of the plant are widely used to treat rheumatism, toothache, neuralgia, and swelling of the throat (Liu et al, 2017). A natural ingredient of toothpaste and soap, NC has great potential value as a component of consumer products.…”

“…As important phase I enzymes, P450 enzymes are responsible for a variety of biotransformations of endogenous substrates and xenobiotics, such as drugs, environmental pollutants, and carcinogens (Liu et al, 2017). However, drug-drug interactions (DDIs) are often caused by inhibition of P450s occurring with the metabolism of commonly used drugs (Danton et al, 2013), which frequently changes their toxicity or efficacy (Haefeli and Carls, 2014).…”