In vitro study on the effect of peucedanol on the activity of cytochrome P450 enzymes

Abstract

Context: Peucedanol is a major extract of Peucedanum japonicum Thunb. (Apiaceae) roots, which is a commonly used herb in paediatrics. Its interaction with cytochrome P450 enzymes (CYP450s) would lead to adverse effects or even failure of therapy. Objective: The interaction between peucedanol and CYP450s was investigated. Materials and methods: Peucedanol (0, 2.5, 5, 10, 25, 50, and 100 lM) was incubated with eight human liver CYP isoforms (CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1), in pooled human liver microsomes (HLMs) for 30 min with specific inhibitors as positive controls and untreated HLMs as negative controls. The enzyme kinetics and time-dependent study (0, 5, 10, 15, and 30 min) were performed to obtain corresponding parameters in vitro. Results: Peucedanol significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC 50 values of 6.03, 13.57, and 7.58 lM, respectively. Peucedanol served as a non-competitive inhibitor of CYP3A4 with a K i value of 4.07 lM and a competitive inhibitor of CYP1A2 and 2D6 with a K i values of 3.39 and 6.77 lM, respectively. Moreover, the inhibition of CYP3A4 was time-dependent with the K i /K inact value of 5.44/0.046 min/lM. Discussion and conclusions: In vitro inhibitory effect of peucedanol on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. As these CYPs are involved in the metabolism of various drugs, these results implied potential drug-drug interactions between peucedanol and drugs metabolized by CYP1A2, 2D6, and 3A4, which needs further in vivo validation.

Peucedanol ameliorates LPS-induced inflammation in RAW264.7 cells and CLP-induced sepsis in mice by inhibiting TLR4/myD88/NF-κB pathway

“…Nowadays, the pharmacological studies on PEU are few. An in vitro study showed that PEU was a non-competitive inhibitor of cytochrome3A4 (CYP3A4) and competitive inhibitors of CYP1A2 and CYP2D6, and its IC 50 values for these three CYP450 enzymes were 6.03, 13.57, and 7.58 μM, respectively [15] . Further, PEU isolated from Toddalia asiatica (L.) Lam.…”

Influence of Gegenqinlian decoction on pharmacokinetics and pharmacodynamics of saxagliptin in type 2 diabetes mellitus rats

“…Nowadays, traditional Chinese medicine (TCM) plays an important role in the treatment of diabetes and often is used to treat T2DM combined with drugs (Cao et al., 2021; Chen et al., 2021; Luo et al., 2022). Gegenqinlian decoction (GQD), a classical prescription of TCM, originated from Shanghanlun and consists of Gegen (Puerariae Lobatae Radix), Huanglian (Coptidis Rhizoma), Huangqin (Scutellariae Radix), and Gancao (Glycyrrhizae Radix et Rhizoma) (Han et al., 2017; Lin et al., 2022; Zhang, Li, et al., 2021). It has multi‐pharmacological effects, such as a lipid‐lowering effect, hypoglycemic effect, and improves intestinal flora (Tian et al., 2021; Zhang, Xu, et al., 2021; Zhou et al., 2021).…”