Inhibition of human cytochrome P450 enzymes by licochalcone A, a naturally occurring constituent of licorice

He, Wei; Wu, Jingjing; Ning, Jing; Hou, Jie; Hong, Xin; He, Yuqi; Ge, Guang-Bo; Xu, Wei

doi:10.1016/j.tiv.2015.06.014

Cited by 54 publications

(48 citation statements)

References 38 publications

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“…In recent years, many studies have demonstrated that crude extracts of licorice and LCA can inhibit the activities of human cytochrome P450 enzymes (CYPs) and P-glycoprotein transporters (P-gps) Qiao et al, 2014;Choi et al, 2013). More recently, we have also found that LCA exhibits broad-spectrum inhibitory effects toward human CYP enzymes including CYP1A2, 2C8, 2C9, 2C19, and 3A4 (He et al, 2015). These studies suggest that LCA can reduce the elimination of many therapeutic drugs that are substrates of CYPs and P-gp, which may cause subsequent HDIs.…”

Section: Introductionmentioning

confidence: 65%

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Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases

Hong

et al. 2016

Food and Chemical Toxicology

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Licochalcone A (LCA) is a major bioactive compound in Licorice, a widely used herbal medicine. In this study, the inhibitory effects of LCA against human UDP-glucuronosyltransferases (UGTs) and LCA associated herb-drug interactions were systematically investigated. Our results demonstrated that LCA displayed broad-spectrum inhibition against human UGTs. LCA exhibited strong inhibitory effects against UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A9, and 2B7 (both IC50 and Ki values lower than 5 μM), while showing moderate inhibitory effects against UGT1A8, 1A10, 2B4, 2B15, and 2B17. The inhibitory effects of LCA against two major UGTs, including UGT1A1 and 1A9, were further investigated in human liver microsomes (HLMs), where the potential risks of LCA via inhibition of UGT1A1 and 1A9 were predicted by combining the in vitro inhibitory data and physiological data. The results from this study also showed that several LCA-containing products were able to increase the area under the curve (AUC) of the substrates that were predominantly metabolized by UGT1A1 or 1A9. These findings together demonstrate that LCA has a potent and broad-spectrum inhibitory effect against most human UGTs and thus suggest that much caution should be exercised when high-dose LCA is co-administered with UGT substrates.

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Section: Introductionmentioning

confidence: 65%

“…It should also be noted that LCA has been identified as a potent inhibitor against human CYP and P-gp (He et al, 2015;. As the most abundant CYP enzyme in the liver, CYP3A4 is the most important phase I metabolic enzyme that involves biotransformation of up to 50% of prescribed drugs and numerous xenobiotic (Dorne et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases

Hong

et al. 2016

Food and Chemical Toxicology

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“…Previously, He et al (2015) reported that licochalcone A strongly inhibited CYP1A2, CYP2C and CYP3A4 (testosterone). In our assay, licochalcone A strongly inhibited CYP2C and CYP3A4 (testosterone), and moderately inhibited CYP1A2, CYP2B6, CYP2D6 and CYP3A4 (midazolam).…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents

Simmler

Chen

et al. 2017

European Journal of Pharmaceutical Sciences

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The potential of licorice dietary supplements to interact with drug metabolism was evaluated by testing extracts of three botanically identified licorice species (Glycyrrhiza glabra L., Glycyrrhiza uralensis Fish. ex DC. and Glycyrrhiza inflata Batalin) and 14 isolated licorice compounds for inhibition of 9 cytochrome P450 enzymes using a UHPLC-MS/MS cocktail assay. G. glabra showed moderate inhibitory effects against CYP2B6, CYP2C8, CYP2C9, and CYP2C19, and weak inhibition against CYP3A4 (testosterone). In contrast, G. uralensis strongly inhibited CYP2B6 and moderately inhibited CYP2C8, CYP2C9 and CYP2C19, and G. inflata strongly inhibited CYP2C enzymes and moderately inhibited CYP1A2, CYP2B6, CYP2D6, and CYP3A4 (midazolam). The licorice compounds isoliquiritigenin, licoricidin, licochalcone A, 18β-glycyrrhetinic acid, and glycycoumarin inhibited one or more members of the CYP2C family of enzymes. Glycycoumarin and licochalcone A inhibited CYP1A2, but only glycycoumarin inhibited CYP2B6. Isoliquiritigenin, glabridin and licoricidin competitively inhibited CYP3A4, while licochalcone A (specific to G. inflata roots) was a mechanism-based inhibitor. The three licorice species commonly used in botanical dietary supplements have varying potential for drug-botanical interactions as inhibitors of cytochrome P450 isoforms. Each species of licorice displays a unique profile of constituents with potential for drug interactions.

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“…Enzyme activity in each well was calculated based on the initial slope of the reaction curve, and percentage of the initial slope of the uninhibited reaction was expressed. The inhibition constant Ki value was determined according to the Dixon method [41].…”

Section: Protease Assaysmentioning

confidence: 99%

Identification and Characterization of ShSPI, a Kazal-Type Elastase Inhibitor from the Venom of Scolopendra Hainanum

Luan

Zhao

Duan

et al. 2019

Toxins

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Elastase is a globular glycoprotein and belongs to the chymotrypsin family. It is involved in several inflammatory cascades on the basis of cleaving the important connective tissue protein elastin, and is strictly regulated to a balance by several endogenous inhibitors. When elastase and its inhibitors are out of balance, severe diseases will develop, especially those involved in the cardiopulmonary system. Much attention has been attracted in seeking innovative elastase inhibitors and various advancements have been taken on clinical trials of these inhibitors. Natural functional peptides from venomous animals have been shown to have anti-protease properties. Here, we identified a kazal-type serine protease inhibitor named ShSPI from the cDNA library of the venom glands of Scolopendra hainanum. ShSPI showed significant inhibitory effects on porcine pancreatic elastase and human neutrophils elastase with Ki values of 225.83 ± 20 nM and 12.61 ± 2 nM, respectively. Together, our results suggest that ShSPI may be an excellent candidate to develop a drug for cardiopulmonary diseases.

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Inhibition of human cytochrome P450 enzymes by licochalcone A, a naturally occurring constituent of licorice

Cited by 54 publications

References 38 publications

Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases

Assessment of the inhibition potential of Licochalcone A against human UDP-glucuronosyltransferases

Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents

Identification and Characterization of ShSPI, a Kazal-Type Elastase Inhibitor from the Venom of Scolopendra Hainanum

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