Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs

  title={Inhibitory Mechanisms of Human CYPs by Three Alkaloids Isolated from Traditional Chinese Herbs},
  author={Yong Zhao and Bent H{\aa}vard Hellum and Aihua Liang and Odd Georg Nilsen},
  journal={Phytotherapy Research},
  pages={825 - 834}
The three purified herbal compounds tetrahydropalmatine (Tet), neferine and berberine (Ber) were explored in vitro for basic inhibition mechanisms towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Positive inhibition controls were used. Mechanism‐based (irreversible) inhibition was assessed… 

Time-dependent Inhibition of CYP2C8 and CYP2C19 by Hedera helix Extracts, A Traditional Respiratory Herbal Medicine

Consumption of herbal medicines or dietary supplements containing H. helix extracts requires careful attention to avoid any CYP-based interactions, as in vitro investigation showed significant inhibitory effects on CYP 2C8, CYP2C19 and CYP1D6 in a concentration-dependent manner.

Modulation of Major Human Liver Microsomal Cytochromes P450 by Component Alkaloids of Goldenseal: Time-Dependent Inhibition and Allosteric Effects

Time-dependent inhibition experiments were conducted to evaluate the ability of berberine and hydrastinine to inhibit major P450 activities in human liver microsomes by using a cocktail of isozyme-specific substrate probes to inform the development of a physiologically based pharmacokinetic model that can be used to predict potential clinically relevant goldenseal-drug interactions.

A Comprehensive Review on the Chemical Properties, Plant Sources, Pharmacological Activities, Pharmacokinetic and Toxicological Characteristics of Tetrahydropalmatine

Pharmacokinetic studies showed that THP was inadequately absorbed in the intestine and had rapid clearance and low bioavailability in vivo, as well as self-microemulsifying drug delivery systems, which could increase the absorption level and absorption rate of THP and improve its bioavailability.

Impact of Tetrahydropalmatine on the Pharmacokinetics of Probe Drugs for CYP1A2, 2D6 and 3A Isoenzymes in Beagle Dogs

The extensive use of Tet and herbal medicines containing Tet makes Tet a candidate for further evaluation of CYP3A‐mediated herb–drug interactions, and in line with previous in vitro findings for its CYP 3A4 inhibition.

Bioactivation of herbal constituents: mechanisms and toxicological relevance

The aim of this review is to provide a cataloging of bioactivation mechanisms of herbal substructures, structure-activity relationships, biological targets, and assist in circumventing the structural liability in the development of more effective and safer herb-based NCEs.

Mechanism-based inactivation of cytochrome P450 enzymes by natural products based on metabolic activation

This review comprehensively classifies natural P450 enzyme inactivators, including terpenoids, phenylpropanoids, flavonoids, alkaloids, and quinones obtained from herbs or foods, as well as the structure − activity correlations according to the IC50 (or Ki ) values reported in the literature.

A Comprehensive Review on Chemical Profiling of Nelumbo Nucifera: Potential for Drug Development

This review highlights potential use of neferine, liensinine, isoliens inine, and nuciferine in clinical trials and mechanism of the potential chemical entities from N.nucifera via structure activity relationship needs to be explored to guarantee the stability and safety for the clinical use.

Drug metabolism and disposition diversity of Ranunculales phytometabolites: a systems perspective

The current knowledge, as well as the challenges around the DMPK (drug metabolism and pharmacokinetics) associated concerns in streamlining drug research and therapeutic use of Ranunculales phytometabolites are highlighted.



The In Vitro Inhibition of Human CYP1A2, CYP2D6 and CYP3A4 by Tetrahydropalmatine, Neferine and Berberine

The in vitro inhibition potential of the three purified herbal constituents tetrahydropalmatine, neferine and berberine towards recombinant human CYP1A2, CYP2D6 and CYP3A4 metabolic activities was investigated.

In vitro inhibition of cytochrome P450 activities by active constituents of Chinese herbal drugs

Naringenin,isorhamnetin,camptothecin,cytosine,berberine,rhein and oleanolic acid have inhibitory effects on the metabolic activities of different CYP isoforms in HLM, and there may be potential drug interactions clinically when these active constituents are used concomitantly with drugs that are metabolized primarily by the CYPs.

In vitro Inhibition of CYP3A4 by the Multiherbal Commercial Product Sambucus Force and its Main Constituents Echinacea purpurea and Sambucus nigra

The CYP3A4 inhibition of Sambucus Force in vitro is considered relatively weak, but recommended high herbal dosages might enhance the potential for clinical interactions, and mechanistic differences are suggested to be caused by herb–herb interactions in the multiherbal product.

Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum.

Nineteen alkamides isolated from Piper nigrum L. were tested for their mechanism-based inhibition on human liver microsomal dextromethorphan O-demethylation activity, a prototype marker for

Repeated administration of berberine inhibits cytochromes P450 in humans

Repeated administration of berberine decreased CYP2D6, 2C9, and CYP3A4 activities, and drug-drug interactions should be considered when berberines is administered.

Mechanism-Based Inhibition of Cytochrome P450 3A4 by Therapeutic Drugs

It appears that the chemical properties of a drug critical to CYP3A4 inactivation include formation of reactive metabolites by CYP isoenzymes, preponderance of CYP inducers and P-glycoprotein (P-gp) substrate, and occurrence of clinically significant pharmacokinetic interactions with coadministered drugs.

[Interaction between four herb compounds and a western drug by CYP3A4 enzyme metabolism in vitro].

  • Guolin ShenA. Liang O. G. Nilsen
  • Biology, Medicine
    Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
  • 2009
Chinese herbal medicinal ingredients effect on the metabolism of CYP3A4 enzyme through 6beta-hydroxy metabolite of testosterone production prompted that drug-interaction could not be apparent between two kinds of Chinese medicines and the CYP4 enzyme substrate, but Neferine could bring about drug-Interaction.

Stereoselective interaction between tetrahydropalmatine enantiomers and CYP enzymes in human liver microsomes.

Investigation of stereoselective metabolism of THP enantiomers in human liver microsomes (HLM) and elucidate which cytochrome P450 (CYP) isoforms contribute to the stereoselectedive metabolism in HLM suggested that THPEnantiomers were predominantly metabolized by CYP3A4/5 and CYP1A2 in H LM, and (+)-THP was preferentially metabolizedBy CYP 1A2.

Inhibition Against Mosquito Cytochrome P450 Enzymes by Rhinacanthin-A, -B, and -C Elicits Synergism on Cypermethrin Cytotoxicity in Spodoptera frugiperda Cells

The combined inhibition effect on mosquito cytochrome P450 enzyme and synergistic effect on Cypermethrin cytotoxicity of the three R. nasutus compounds could be beneficial for resistance management strategies in mosquito vector control.

The two enantiomers of tetrahydropalmatine are inhibitors of P-gp, but not inhibitors of MRP1 or BCRP

The present study showed the stereoselective interaction between THP enantiomers and P-gp, which should be considered in clinical practice.