Pogostone inhibits the activity of CYP3A4, 2C9, and 2E1 in vitro

Abstract

Context: Pogostone possesses various pharmacological activities, which makes it widely used in the clinic. Its effect on the activity of cytochrome P450 enzymes (CYP450s) could guide its clinical combination. Objective: To investigate the effect of pogostone on the activity of human CYP450s. Materials and methods: The effect of pogostone on the activity of CYP450s was evaluated in human liver microsomes (HLMs) compared with blank HLMs (negative control) and specific inhibitors (positive control). The corresponding parameters were obtained with 0-100 lM pogostone and various concentrations of substrates.Results: Pogostone was found to inhibit the activity of CYP3A4, 2C9, and 2E1 with the IC 50 values of 11.41, 12.11, and 14.90 lM, respectively. The inhibition of CYP3A4 by pogostone was revealed to be performed in a non-competitive and time-dependent manner with the K i value of 5.69 lM and the KI/K inact value of 5.86/0.056/(lM/min). For the inhibition of CYP2C9 and 2E1, pogostone acted as a competitive inhibitor with the K i value of 6.46 and 7.67 lM and was not affected by the incubation time. Discussion and conclusions: The inhibitory effect of pogostone on the activity of CYP3A4, 2C9, and 2E1 has been disclosed in this study, implying the potential risk during the co-administration of pogostone and drugs metabolized by these CYP450s. The study design provides a reference for further in vivo investigations to validate the potential interaction.

Potential herb–drug interactions between anti-COVID-19 drugs and traditional Chinese medicine

“…P-gp and MRP are involved in the transmembrane process of patchouli alcohol 268 . In vitro , pogostone displays inhibitory effects on human CYP3A4, 2C9 and 2E1 269 . Pogostemonis Herba could modulate intestinal microbiota, such as Anaerostipes butyraticus , Butytivibrio fibrisolvens , Clostridium jejuense , Eubacterium uniforme , and Lactobacillus lactis which are the main producing bacteria for SCFAs 270 .…”

“… 92 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ) 1A2↑ 2A1↑ 2B1↑ 2B9↑ 3A↑ 3A4↑ Extract 2B6↓ 2C9↓ 2C19↓ 3A4↓ Glycyrrhetinic acid 2C9 a 2C19 a 3A4 a 1A3↓ 2B7↓ CES1↓ P-gp a Glycyrrhizin 1A2↑ 2A1↑ 2B1↑ 2B9↑ 3A↑ 3A4↑ Licochalcone A 1A2↓ 2D6↓ 2E1↓ 2C19↓ 2C8↓ 2C9↓ 3A4↓ 1B1↓ Glycyrol 2C9↓ Pogostemonis Herba (Refs. 268 , 269 ) Patchouli alcohol …”

Amphiphilic Mesoporous Foam-Stabilized Pickering Emulsions as Versatile Nanoreactors for In Vitro Drug Metabolism

“…Monooxygenase reaction is the most common reaction catalyzed by CYP450s, for example, one atom of oxygen is inserted into the aliphatic position of an organic substrate (RH), while the other oxygen atom is reduced to water . Since CYP450s are involved in multi-component electron transfer chains in drug metabolism, the activity of CYP450s is vital in the catalytic metabolism . In vivo, CYP450s are located on the endoplasmic or mitochondrial membrane of liver cells; the metabolism between drug and multi-enzymes occurs in a confined environment and has fast reaction rates. , Unlike in the living body, most in vitro metabolic reactions exhibit slow kinetics.…”

“…10 Since CYP450s are involved in multi-component electron transfer chains in drug metabolism, the activity of CYP450s is vital in the catalytic metabolism. 11 In vivo, CYP450s are located on the endoplasmic or mitochondrial membrane of liver cells; the metabolism between drug and multi-enzymes occurs in a confined environment and has fast reaction rates. 12,13 Unlike in the living body, most in vitro metabolic reactions exhibit slow kinetics.…”