In Vitro Metabolism of Auriculasin and Its Inhibitory Effects on Human Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes

Shi, Xianbao; Zhang, Gang; Ge, Guang-Bo; Guo, Zhe; Song, Yonggui; Su, Dan; Shan, Lina

doi:10.1021/acs.chemrestox.9b00307

Cited by 11 publications

(6 citation statements)

References 37 publications

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“…To further explore the changes of related genes in serum metabolites caused by glucose-lowering as well as lipid invariability affected by RC, we carried out RNA-Seq technology of the liver tissue (Supplementary Materials and Methods in Supplementary Information ). Since most drugs are eliminated from the body by hepatic metabolism, we sequenced the total RNA in the liver tissue [ 30 , 31 ]. The PCA scoring diagram helped to differentiate among the three groups.…”

Section: Resultsmentioning

confidence: 99%

Obese rats intervened with Rhizoma coptidis revealed differential gene expression and microbiota by serum metabolomics

Luo

Zhang

et al. 2021

BMC Complement Med Ther

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Background Integrating systems biology is an approach for investigating metabolic diseases in humans. However, few studies use this approach to investigate the mechanism by which Rhizoma coptidis (RC) reduces the effect of lipids and glucose on high-fat induced obesity in rats. Methods Twenty-four specific pathogen-free (SPF) male Sprague–Dawley rats (80 ± 10 g) were used in this study. Serum metabolomics were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry. Liver tissue and cecum feces were used for RNA-Seq technology and 16S rRNA gene sequencing, respectively. Results We identified nine potential biomarkers, which are differential metabolites in the Control, Model and RC groups, including linoleic acid, eicosapentaenoic acid, arachidonic acid, stearic acid, and L-Alloisoleucine (p < 0.01). The liver tissue gene expression profile indicated the circadian rhythm pathway was significantly affected by RC (Q ≤ 0.05). A total of 149 and 39 operational taxonomic units (OTUs), which were highly associated with biochemical indicators and potential biomarkers in the cecum samples (FDR ≤ 0.05), respectively, were identified. Conclusion This work provides information to better understand the mechanism of the effect of RC intervention on hyperlipidemia and hypoglycemic effects in obese rats. The present study demonstrates that integrating systems biology may be a powerful tool to reveal the complexity of metabolic diseases in rats intervened by traditional Chinese medicine.

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Section: Resultsmentioning

confidence: 99%

Obese rats intervened with Rhizoma coptidis revealed differential gene expression and microbiota by serum metabolomics

Luo

Zhang

et al. 2021

BMC Complement Med Ther

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“…Differences in K m value have shown significance to comprehend the basis of species-related differences in P450-catalyzed drug oxidation reactions [ 35 ]. Similar K m values among various species reflect equivalent binding affinities toward the metabolic site and indicate species similarities [ 36 ]. The comparable K m values for the formation of P 1 in MLMs and HLMs in this study evidenced similar CYPs affinity in these two mammals.…”

Section: Discussionmentioning

confidence: 99%

An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone

Qin

Zhu

Xue

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Kurarinone is a major component found in the dried roots of Sophora flavescens Ait. that participates in vital pharmacological activities. Recombinant CYP450 supersomes and liver microsomes were used to study the metabolic profiles of kurarinone and its inhibitory actions against cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes. 100 μM of kurarinone strongly inhibited more than 90% of UGT1A1, UGT1A6, CYP1A2, and CYP2C9. CYP1A2 and CYP2D6 played important roles in catalyzing the biotransformation of kurarinone. Moreover, metabolism of kurarinone considerably differs among species, and metabolic characteristics were similar between monkey and human. Kurarinone demonstrated moderate permeability at values of pH 4.0 and 7.4. Our findings offer a clearer idea to understand the pharmacological and toxicological mechanisms of kurarinone.

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“…The specific inhibitors for CYP2C9, CYP1A2, CYP2C19, CYP2D6, CYP2E1 and CYP3A were sulphaphenazole (10 μM), furafylline (10 μM), omeprazole (20 μM), quinidine (10 μM), clomethiazole (50 μM) and ketoconazole (1 μM) (Shi et al. 2019 ). Clobetasol propionate inhibited CYP3A5 with an IC50 of 0.32 μM (Wang et al.…”

Section: Methodsmentioning

confidence: 99%

In vitro differences in toddalolactone metabolism in various species and its effect on cytochrome P450 expression

Shan¹,

Shi²,

Hu³

et al. 2022

Pharmaceutical Biology

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Context Toddalolactone, the main component of Toddalia asiatica (L.) Lam. (Rutaceae), has anticancer, antihypertension, anti-inflammatory, and antifungal activities. Objective This study investigated the metabolic characteristics of toddalolactone. Materials and methods Toddalolactone metabolic stabilities were investigated by incubating toddalolactone (20 μM) with liver microsomes from humans, rabbits, mice, rats, dogs, minipigs, and monkeys for 0, 30, 60, and 90 min. The CYP isoforms involved in toddalolactone metabolism were characterized based on chemical inhibition studies and screening assays. The effects of toddalolactone (0, 10, and 50 µM) on CYP1A1 and CYP3A5 protein expression were investigated by immunoblotting. After injecting toddalolactone (10 mg/kg), in vivo pharmacokinetic profiles using six Sprague–Dawley rats were investigated by taking 9-time points, including 0, 0.25, 0.5, 0.75, 1, 2, 4, 6 and 8 h. Results Monkeys showed the greatest metabolic capacity in CYP-mediated and UGT-mediated reaction systems with short half-lives ( T 1/2 ) of 245 and 66 min, respectively, while T 1/2 of humans in two reaction systems were 673 and 83 min, respectively. CYP1A1 and CYP3A5 were the major CYP isoforms involved in toddalolactone biotransformation. Induction of CYP1A1 protein expression by 50 μM toddalolactone was approximately 50% greater than that of the control (0 μM). Peak plasma concentration ( C max ) for toddalolactone was 0.42 μg/mL, and T max occurred at 0.25 h post-dosing. The elimination t 1/2 was 1.05 h, and the AUC 0–t was 0.46 μg/mL/h. Conclusions These findings demonstrated the significant species differences of toddalolactone metabolic profiles, which will promote appropriate species selection in further toddalolactone studies.

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In Vitro Metabolism of Auriculasin and Its Inhibitory Effects on Human Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes

Cited by 11 publications

References 37 publications

Obese rats intervened with Rhizoma coptidis revealed differential gene expression and microbiota by serum metabolomics

Obese rats intervened with Rhizoma coptidis revealed differential gene expression and microbiota by serum metabolomics

An In Vitro Study for Evaluating Permeability and Metabolism of Kurarinone

In vitro differences in toddalolactone metabolism in various species and its effect on cytochrome P450 expression

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