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In vitro inhibition of human cytochrome P450 enzymes by licoisoflavone B from Glycyrrhiza uralensis Fisch. ex DC.

ABSTRACT: Glycyrrhiza uralensis Fisch. ex DC, one of the 3 pharmacopeial species of licorice and widely used in dietary supplements, can inhibit certain cytochrome P450 (CYP) enzymes. Thereby, G. uralensis preparations have the potential to cause pharmacokinetic drug interactions when consumed along with prescription medicines. One compound (1.34 mg dry weight) responsible for inhibiting CYP2B6, CYP2C8, and CYP2C9 was isolated using bioactivity-guided fractionation from 250 g dried roots, stolons, and rhizomes. The enzyme kinetics and mechanisms of inhibition were determined using human liver microsomes, recombinant enzymes, and UHPLC-MS/MS-based assays. Identified as licoisoflavone B, this compound displayed reversible inhibition of CYP2C8 with an IC50 value of 7.4 ± 1.1 µM and reversible inhibition of CYP2C9 with an IC50 value of 4.9 ± 0.4 µM. The enzyme kinetics indicated that the mechanism of inhibition was competitive for recombinant CYP2C8, with a Ki value of 7.0 ± 0.7 μM, and mixed-type inhibition for recombinant CYP2C9, with a Ki value of 1.2 ± 0.2 μM. Licoisoflavone B moderately inhibited CYP2B6 through a combination of irreversible and reversible mechanisms with an IC50 value of 16.0 ± 3.9 µM.

SUBMITTER: Chen L

PROVIDER: S-EPMC10613970 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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In vitro inhibition of human cytochrome P450 enzymes by licoisoflavone B from Glycyrrhiza uralensis Fisch. ex DC.

Chen Luying L Nikolic Dejan D Li Guannan G Liu Jialin J van Breemen Richard B RB

Toxicological sciences : an official journal of the Society of Toxicology 20231001 1

Glycyrrhiza uralensis Fisch. ex DC, one of the 3 pharmacopeial species of licorice and widely used in dietary supplements, can inhibit certain cytochrome P450 (CYP) enzymes. Thereby, G. uralensis preparations have the potential to cause pharmacokinetic drug interactions when consumed along with prescription medicines. One compound (1.34 mg dry weight) responsible for inhibiting CYP2B6, CYP2C8, and CYP2C9 was isolated using bioactivity-guided fractionation from 250 g dried roots, stolons, and rhi ...[more]

PMID: 37535691

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Project description:Glycyrrhiza uralensis Fisch. is known as a common Chinese medicinal herb used to harmonize the effects of other ingredients in most Chinese herbal prescriptions. The rapid production of flavonoids in vitro remains unknown in G. uralensis Fisch. To investigate the in vitro adventitious root regeneration and flavonoid accumulation characteristics in G. uralensis for restrictions on collecting wild plants, suspension cultural and freezing microtomy with histochemical assays were carried out. We reported that multiple adventitious roots were initiated from hypocotyls and stems of G. uralensis. Indole-3-butyric acid (IBA) was more conducive than NAA (1-naphthaleneacetic acid) in inducing G. uralensis adventitious roots, but the addition of 6-BA (6-benzylaminopurine) and KT (kinetin) suppressed the formation of adventitious roots. While the concentration of IBA was 1.0 mg L-1, the flavonoid content and yield were the highest at 19.96 mg g-1 and 1.23 mg g-1, respectively. The optimum medium for adventitious root induction was 1/4-strength Murashige and Skoog's medium containing 0.1 mg L-1 IBA. The content of flavonoids in adventitious roots and apicals cultured in vitro was higher than that in suspension callus, reaching 3.87 times the callus flavonoid content. The histochemical localization of flavonoids showed that G. uralensis flavonoids mainly distributed in the epidermal parenchyma cells of the callus outer layers and gradually accumulated in cell wall and cell gaps of the epidermis and endodermis of adventitious roots along with the primary growth of adventitious roots, indicating that there were no flavonoids in the roots at the early stage of adventitious roots formation. The results showed that calli inducing adventitious roots and apicals for 30 days obtained the highest yield of flavonoid, indicating effective production for flavonoids instead of wild culture. AlCl3 ethanol solution was better than NaOH aqueous solution in terms of chromogenic and localization effects. We concluded that the highest yield of flavonoid and effective production for flavonoid instead of wild culture could be obtained from calli inducing adventitious roots and apicals.

Dataset Information

In vitro inhibition of human cytochrome P450 enzymes by licoisoflavone B from Glycyrrhiza uralensis Fisch. ex DC.

Publications

In vitro inhibition of human cytochrome P450 enzymes by licoisoflavone B from Glycyrrhiza uralensis Fisch. ex DC.

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