scholarly journals Material Basis For Combining Euphrobia Kansui And Licorice Based On Rat Liver Microsomal

2021 ◽  
Author(s):  
Tingting Wang ◽  
Haoyue Li ◽  
Cheng Shi ◽  
Lei Hao ◽  
Yanrui Liu ◽  
...  
Keyword(s):  
Rat Liver ◽  
Glycyrrhizic Acid ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Glycyrrhetinic Acid ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Metabolic Substrates ◽  
Synergistic Mechanism ◽  
Main Component

Abstract Background: The herbal-pair, Kansui and Licorice, belongs to the "eighteen incompatible medicaments" category of traditional Chinese medicine. Kansuiphorin C (KC) is the main toxic component of Kansui. The main component of licorice is glycyrrhizic acid, which is hydrolyzed to glycyrrhetinic acid. Currently, the synergistic mechanism between Kansui and Licorice is unclear. Methods: Rat liver microsomes were used in this experiment, HPLC was used to detect the contents of KC, glycyrrhizic acid, and glycyrrhetinic acid to determine whether these compounds are metabolic substrates of CYP450. A control group with isozyme inhibitors was also employed to reveal the isozyme subtypes involved in compound metabolism. To further explain the induction or inhibitory effect of the above compounds on liver microsomal enzymes, enzyme activity was indirectly revealed based on changes in the contents of known metabolites of CYP2E1, CYP2C9, and CYP3A4. Results: KC and glycyrrhetinic acid were metabolic substrates of CYP450. CYP2E1 and CYP2C9 are mainly involved in the partial metabolism of glycyrrhizic acid in the liver. CYP2E1 and CYP3A4 are mainly involved in the partial metabolism of glycyrrhetinic acid in the liver. CYP2E1, CYP2C9, and CYP3A4 did not play a major role in the metabolism of KC. KC had little effect on the metabolism of glycyrrhizic acid and glycyrrhetinic acid. Glycyrrhizic acid, glycyrrhetinic acid, and KC induced CYP3A4 and inhibit CYP2E1. Both glycyrrhizic acid and glycyrrhetinic acid could inhibit the induction of CYP3A4 after combination with KC. KC with glycyrrhizic acid could synergistically inhibit the activity of CYP2E1, while KC with glycyrrhetinic acid could synergistically induce the activity of CYP2E1 Conclusion: KC and glycyrrhetinic acid were metabolic substrates of CYP450. KC, glycyrrhizic acid and glycyrrhetinic acid have different inducing and inhibiting effects on CYP450 enzyme.

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

Inhibitory effect of silybin on pharmacokinetics of imatinib in vivo and in vitro

2014 ◽  
Vol 92 (11) ◽  
pp. 961-964 ◽  
Author(s):  
Li Wang ◽  
Zhe Wang ◽  
Meng-ming Xia ◽  
Ying-ying Wang ◽  
Hai-yun Wang ◽  
...  
Keyword(s):  
Single Dose ◽  
Rat Liver ◽  
Liver Microsome ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Multiple Doses

The objective of this work was to investigate the effect of orally administered silybin on the pharmacokinetics of imatinib in rats and the metabolism of imatinib in human liver microsome and rat liver microsomes. Eighteen healthy male SD rats were randomly divided into 3 groups: group A (control group), group B (received multiple doses of 50 mg·kg−1 silybin for 15 consecutive days), and group C (received a single dose of 50 mg·kg−1 silybin). A single dose of imatinib was administered orally 30 min after administration of silybin (50 mg·kg−1). Imatinib plasma levels were measured by UPLC-MS/MS, and pharmacokinetic parameters were calculated by DAS 3.0 software (Bontz Inc., Beijing, China). In addition, human and rat liver microsome were performed to determine the effects of silybin metabolism of imatinib in vitro. The multiple doses or single dose of 50 mg·kg−1 silybin significantly decreased the area under the curve (0-t) of imatinib (p < 0.01). And the half-life (t1/2) of imatinib is significantly increased (p < 0.05 and p < 0.01, respectively). Also, silybin showed inhibitory effect on human and rat microsomes, the IC50 of silybin were 26.42 μmol·L−1 and 49.12 μmol·L−1 in human and rat liver microsomes, respectively. These results indicate that more attention should be paid to when imatinib is administrated combined with silybin.

Autoregulation of 3, 3′,5′-triiodothyronine production by rat liver microsomes

1981 ◽  
Vol 98 (2) ◽  
pp. 240-245 ◽  
Author(s):  
T. Kaminski ◽  
J. Köhrle ◽  
R. Ködding ◽  
R.-D. Hesch
Keyword(s):  
Rat Liver ◽  
Incubation Medium ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Incubation Mixture ◽  
Rat Liver Microsomes ◽  
Experimental Conditions ◽  
Physiological Concentration ◽  
Enzyme Binding ◽  
Ph Dependent

Abstract. Conversion of thyroxine (T4) to 3,3′,5′-triiodothyronine (rT3) was studied in rat liver microsomes. Addition of rT3 at a physiological concentration to the incubation medium inhibited the deiodination of thyroxine to rT3. With a concentration of rT3 greater than 37.6 nM no net rT3 production at pH 8.0 was observed. Further increases in rT3 concentration resulted only in degradation of added rT3 and no net synthesis of rT3 from T4 could be detected. The inhibitory effect of rT3 upon its own production from T4 was pH dependent, 5 fold lower amounts of hormone being required to inhibit completely rT3 production at pH 7.4 than at pH 8.0. With the same experimental conditions no significant effect of rT3 on the conversion of T4 to 3,5,3′-triiodothyronine (T3) could be observed at pH 8.0 with all concentrations of added iodothyronine. A linear production of 3,3′-T2 from added rT3 was determined over the whole range of rT3 concentration, suggesting a lack of saturation of deiodinating enzyme. Binding of rT3 by anti-rT3 antibody added to the incubation mixture enhanced rT3 production from T4 by protecting rT3 from being degraded and/or diminishing the inhibitory effect of this iodothyronine on its own production. It was concluded that rT3 influenced its own production and that this effect may represent an important autoregulatory process in the iodothyronine metabolism.

scholarly journals Modulation of rat hepatic CYP3A4 activity by Brassica oleracea, Hibiscus rosa sinensis, and Tradescantia zebrina

2020 ◽  
Vol 11 (1) ◽  
pp. 7453-7459
Keyword(s):  
Brassica Oleracea ◽  
Rat Liver ◽  
Chinese Cabbage ◽  
Methanol Extract ◽  
Liver Microsomes ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Cyp3a4 Activity ◽  
Yellow Flower ◽  
Hibiscus Rosa Sinensis

One of the major cytochrome P450s, CYP 3A4, is known to be involved in herb-drug and food-drug interactions. The objective of this study was to examine the in vitro effect of Brassica oleracea L. var. pekinensis (Chinese cabbage) juice, methanol extract of Hibiscus rosa sinensis (Hibiscus) yellow flower and Tradescantia zebrina pendula leaves, respectively on CYP 3A4 activity in rat liver microsomes. Differential centrifugation method was used to isolate microsomes from the rat livers. The concentration of formaldehyde released from N-demethylation of aminopyrine in rat liver microsomes was determined. Based on the results obtained, B. oleracea juice at 100 ng/mL and 1000 g/mL significantly reduced CYP3A4 activity when compared to the control group. On the other hand, methanol extract of Hibiscus yellow flower and T. zebrina leaves at 1, 10, 100, and 1000 ng/mL significantly increased the metabolism of aminopyrine by enhancing CYP3A4 activity when compared to the control group. Our findings suggested that Chinese cabbage juice, methanol extract of Hibiscus yellow flower, and T. zebrina leaves could have the potential to interact with the metabolism of aminopyrine in rat liver microsomes by modulating the hepatic CYP activity.

Inhibitory effect of curcumin on fatty acid desaturation inMortierella alpina 1S-4 and rat liver microsomes

Lipids ◽  
1992 ◽  
Vol 27 (7) ◽  
pp. 509-512 ◽  
Author(s):  
Sakayu Shimizu ◽  
Saeree Jareonkitmongkol ◽  
Hiroshi Kawashima ◽  
Kengo Akimoto ◽  
Hideaki Yamada
Keyword(s):  
Fatty Acid ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Fatty Acid Desaturation ◽  
Rat Liver Microsomes

scholarly journals Structure-related inhibitory effect of antimicrobial enoxacin and derivatives on theophylline metabolism by rat liver microsomes.

1996 ◽  
Vol 40 (8) ◽  
pp. 1875-1880 ◽  
Author(s):  
Y Mizuki ◽  
I Fujiwara ◽  
T Yamaguchi ◽  
Y Sekine
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Molecular Characteristics ◽  
Rat Liver Microsomes ◽  
Difference Spectra ◽  
Metabolite Formation ◽  
Molecular Conformations ◽  
Theophylline Metabolism ◽  
Cytochrome P 450

Enoxacin, an antimicrobial fluoroquinolone with a 7-piperazinyl-1, 8-naphthyridine skeleton, is a potent inhibitor of cytochrome P-450-mediated theophylline metabolism. The present study was designed to clarify, using seven enoxacin derivatives, the molecular characteristics of the fluoroquinolone responsible for the inhibition. Three derivatives with methyl-substituted 7-piperazine rings inhibited rat liver microsomal theophylline metabolism to 1,3-dimethyluric acid to an extent similar to that of enoxacin (50% inhibitory concentrations [IC50s] = 0.39 to 0.48 mM). 7-Piperazinyl-quinoline derivatives, 8-hydroenoxacin (8-Hy) and 1-cyclopropyl-8-fluoroenoxacin (8-F1), which have a hydrogen and a fluorine at position 8, respectively, more weakly inhibited metabolite formation (IC50s = 0.88 and 1.29 mM, respectively). Little inhibition (IC50 > 2 mM) was observed in those with 3'-carbonyl and 4'-N-acetyl groups on the piperazine rings. The substrate-induced difference spectra demonstrated that the affinities of enoxacin, 8-Hy, and 8-F1 to cytochrome P-450 were parallel with their inhibitory activities. The substituent at position 8 was found to determine the molecular conformations of the fluoroquinolones, and the planarity in molecular shape decreased in the same order as the inhibitory activity (enoxacin > 8-Hy > 8-F1). Moreover, the 3'-carbonyl and 4'-N-acetyl groups decreased the basicity of their vicinal 4'-nitrogen atoms when judged from their electrostatic potentials, which showed a remarkably broadened negative charge around the nitrogens. As a result, the planarity of the whole molecule and the basicity of the 4'-nitrogen atom of enoxacin are likely to be dominant factors in the inhibition of theophylline metabolism by cytochrome P-450.

Sign in / Sign up

Export Citation Format

Share Document