Effects of Schizonepetin on Activity and mRNA Expression of Cytochrome P450 Enzymes in Rats

Bao, Beihua; Geng, Tao; Cao, Yudan; Yao, Weifeng; Zhang, Li; Ding, Anwei

doi:10.3390/ijms131217006

Cited by 11 publications

(5 citation statements)

References 14 publications

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“…The expression of individual CYPs is regulated by both endogenous and xenobiotic factors, including drugs and natural compounds. During drug development, in order to avoid undesirable drug–drug/herb interactions that may lead to changes in the rate of drug metabolism and potentially contribute to drug toxicity, it is helpful to acquire a preliminary understanding of the metabolism of a new chemical compound and its affinity for certain metabolic enzymes [9]. Moreover, transporter-mediated efflux of exogenous compounds and metabolites is an important cellular defense mechanism and plays a central role in the barrier and excretory functions in tissues, such as the intestinal mucosa, blood–brain and blood–testis barriers, renal proximal tubules, and liver.…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity and pharmacokinetic characterization of Cereus jamacaru ethanolic extract in rats

Medeiros

Bortolin

et al. 2019

Bioscience Reports

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The effect of Cereus jamacaru ethanolic extract in rats was analyzed using genotoxicity assays and liver ABCB1 and CYP2D4 gene expression. The lyophilized extract of C. jamacaru cladodes was analyzed with LC–MS/MS. Male Wistar rats (n=36) were equally distributed into six groups that did (+) or did not (−) receive cyclophosphamide treatments: Control (−); Control (+); EXP 1 (−), and EXP 1 (+), both treated with 210 mg/kg of ethanolic extract; and EXP 2 (−) and EXP 2 (+), both treated with 420 mg/kg of ethanolic extract. After 30 d of treatment, body weight and food and water intake were monitored. Right femur of the rats and spinal canal fluid were harvested and used for genotoxicity assays, and the liver samples were used for gene expression studies. The phytochemical analysis identified novel compounds. Animals treated with C. jamacaru showed lower body weight and food ingestion compared to controls (P<0.05). The genotoxicity assay showed an absence of ethanolic extract cytotoxicity. CYP2D4 expression was higher in EXP 2 groups compared with EXP 1 (−) group (P<0.05). ABCB1A expression was higher in negative groups compared with the positive groups. These results indicated a new phytochemical characterization of C. jamacaru and its effect on food ingestion and body weight gain. Moreover, the genotoxicity assay suggested that C. jamacaru ethanolic extract treatment presents significant intrinsic genotoxic potential and the enhanced expression of ABCB1 and CYP2D4 on C. jamacaru extract treatment suggests a role of the efflux transporter and microsomal enzyme, respectively, in C. jamacaru pharmacokinetics.

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Section: Introductionmentioning

confidence: 99%

Genotoxicity and pharmacokinetic characterization of Cereus jamacaru ethanolic extract in rats

Medeiros

Bortolin

et al. 2019

Bioscience Reports

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“…Among numerous CYP isozymes identified to date, three human hepatic CYP isozymes (CYP1A2, 2C9, and 3A4) play the dominant roles (Nelson et al , ), among which CYP3A (~30% of total CYPs) and CYP2C (~20%) enzymes are the major isozymes followed by CYP1A2 (~13%) (Shimada et al , ). The activities of CYP isozymes can be inhibited or induced either by foods, drug entities, or herbal products (Bao et al , ; Gao et al , ; Han et al , ; Hanley et al , ; Su et al , ; Ueng et al , ; Yamasaki et al , ), consequently resulting in significant and unwanted side effects or therapeutic failure. Therefore, precise and reliable estimations of the in vivo activity of individual CYP isoforms are essential for the evaluation of herb–drug interactions.…”

Section: Introductionmentioning

confidence: 99%

Effects of Vitexin on the Pharmacokinetics and mRNA Expression of CYP Isozymes in Rats

Wang

Chen

et al. 2014

Phytother. Res.

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In traditional therapy with Chinese medicine, vitexin has several pharmacological properties, including antinociceptive, antispasmodic, antioxidant, antimyeloperoxidase, and α-glucosidase inhibitory activities. Recently, vitexin was shown to protect the heart against ischemia/reperfusion injury in an in vitro model by inhibiting apoptosis. The purpose of this study was to find out whether vitexin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (10 mg/kg), tolbutamide (1 mg/kg), and midazolam (5 mg/kg), was given as oral administration to rats treated with short or long period of intravenous vitexin via the caudal vein. Blood samples were collected at a series of time points, and the concentrations of probe drugs in plasma were determined by HPLC-mass spectrometry (MS)/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time reverse transcription-polymerase chain reaction was performed to determine the effects of vitexin on the mRNA expression of CYP1A2, CYP2C11, and CYP3A1 in rat liver. Treatment with short or long period of vitexin had no effects on rat CYP1A2. However, CYP3A1 enzyme activity was inhibited by vitexin in a concentration-dependent and time-dependent manner. Furthermore, CYP2C11 enzyme activity was induced after short period treatment but inhibited after long period of vitexin treatment. The mRNA expression results were in accordance with the pharmacokinetic results. In conclusion, vitexin can either inhibit or induce activities of CYP2C11 and CYP3A1. Therefore, caution is needed when vitexin is co-administered with some CYP2C11 or CYP3A1 substrates in clinic, which may result in treatment failure and herb-drug interactions.

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“…Cyp1a2 is the most important Cyp1a member in human beings, constituting approximately 13% of the total Cyp superfamily. Numerous studies indicated that Cyp1a2 plays a pivotal role in the metabolism of the clinically used medications such as phenacetin, verapamil, acetaminophen, propranolol, imipramine, and foodborne procarcinogens including imidazoquinoline derivatives and polycyclic aromatic hydrocarbons (Bao et al, 2012;Gao et al, 2014). Moreover, Cyp1a2 was identified to participate in the metabolism of amounts of natural compounds, such as estragole and aristolochic acids (Rendic, 2002), and several important endogenous substrates, such as arachidonic acid, estrone, estradiol and melatonin (Zhou et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

Effects of tetrahydroxystilbene glucoside on mouse liver cytochrome P450 enzyme expressions

et al. 2014

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1. To investigate the effects of tetrahydroxystilbene glucoside (TSG), the main active component of Polygonum multiflorum, on mouse liver cytochrome P450 (Cyp) enzyme protein expressions. Male mice were randomly divided into the control, TSG low (10 mg/kg) and high dose (40 mg/kg) groups. After TSG intragastrical administration for 3, 5 and 7 d, mice were sacrificed and the mouse body and liver weight were detected. The Cyp enzymes and various transcription factors such as AhR, PXR and PPARα protein expressions in mouse livers were measured by Western blotting assay. 2. No significant difference of mouse body and liver weight between the control and TSG treatment groups was detected. Additionally, TSG decreased Cyp1a2 and Cyp2e1 protein expressions after TSG treatment for 3, 5 and 7 d, respectively. Moreover, TSG suppressed Cyp3a11 protein expression after TSG treatment for 5 and 7 d. Furthermore, TSG high dose inhibited AhR and PXR protein expressions after TSG treatment for 5 and 7 d, while both TSG low dose and high dose obviously decreased PPARα protein level from TSG treatment for 3 d. 3. TSG has inhibitory effects on mouse liver Cyp1a2, Cyp2e1 and Cyp3a11 protein expressions through the suppression of AhR, PXR and PPARα activation.

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Effects of Schizonepetin on Activity and mRNA Expression of Cytochrome P450 Enzymes in Rats

Cited by 11 publications

References 14 publications

Genotoxicity and pharmacokinetic characterization of Cereus jamacaru ethanolic extract in rats

Genotoxicity and pharmacokinetic characterization of Cereus jamacaru ethanolic extract in rats

Effects of Vitexin on the Pharmacokinetics and mRNA Expression of CYP Isozymes in Rats

Effects of tetrahydroxystilbene glucoside on mouse liver cytochrome P450 enzyme expressions

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