Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes

Hou, Meiling; Chang, Li-Wen; Lin, Chi‐Hung; Lin, Lie‐Chwen; Tsai, Tung Hu

doi:10.1016/j.jep.2014.07.022

Cited by 14 publications

(6 citation statements)

References 39 publications

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“…According to the dose translation (Reagan-Shaw et al, 2008) from human to animal, the calculated oral dose of SHXXT (0.5 g/kg) was equivalent to the rhein administration dose of 1 mg/kg. Second, in our previous study (Hou et al, 2014a) on gene expression profiling in drugmetabolizing genes after SHXXT treatment, the results of microarray analysis demonstrated that Cyp7a1, Cyp2c6, Atp1b1, and Slc7a2 were upregulated by approximately 2-fold; however, Ces2e was downregulated by 19-fold post-7 days of SHXXT treatment. Thus, based on the clinical application of SHXXT and our previous experimental evidence, rhein at doses of 1 and 10 mg/kg was given orally for 7 days to explore the herb-drug interactions of rhein on the PK and PD of clozapine in the rat mPFC.…”

Section: Methodsmentioning

confidence: 92%

“…for cannulation. The detailed procedures of cannulation were performed as in a previous study (Hou et al, 2014a). Additionally, 10 rats per group were used for in vivo microdialysis study.…”

Section: Methodsmentioning

confidence: 99%

“…Fluoxetine and cimetidine, and to a lesser extent valproate, inhibit the activities of cytochrome P450 enzymes, which will increase the levels of clozapine and its metabolites (Watras and Taylor, 2013;Victoroff et al, 2014). Studies on the comparative pharmacokinetics (PK) of rhein in normal and constipated rats have demonstrated that loperamide-induced constipation reduced the absorption of rhein (Hou et al, 2014a). Additionally, investigations on gene expression by microarray analysis indicate that five drug-metabolizing genes such as Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly altered by the San-Huang-Xie-Xin-Tang (SHXXT) treatment (Hou et al, 2014a).…”

Section: Introductionmentioning

confidence: 99%

“…Studies on the comparative pharmacokinetics (PK) of rhein in normal and constipated rats have demonstrated that loperamide-induced constipation reduced the absorption of rhein (Hou et al, 2014a). Additionally, investigations on gene expression by microarray analysis indicate that five drug-metabolizing genes such as Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly altered by the San-Huang-Xie-Xin-Tang (SHXXT) treatment (Hou et al, 2014a). SHXXT, a medicinal herbal product used as a remedy for constipation, consists of rhizomes of R. palmatum L., roots of Scutellaria baicalensis Georgi, and rhizomes of Coptis deltoidea C. Y. Cheng & P. K. Hsiao, with a weight ratio of 2:1:1, respectively.…”

Section: Introductionmentioning

confidence: 99%

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The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

Hou

Lin

et al. 2015

J Pharmacol Exp Ther

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Clozapine, an atypical antipsychotic agent, is highly effective in treatment-resistant schizophrenia; however, its major side effect is constipation. Instead of laxatives, rhein is a pharmacologically active component found in Rheum palmatum L., a medicinal herbal remedy for constipation. The purpose of this study is to determine whether rhein impacts the pharmacokinetics (PK) and pharmacodynamics (PD) of clozapine in brain when used to relieve clozapine-induced constipation. Here, we have investigated not only the PK of clozapine in blood but also the effects of rhein on the PK of clozapine in blood and in brain extracellular fluid together with the PD effects on neurotransmitters in extracellular fluid. The concentrations of clozapine and norclozapine in biologic samples were measured by ultra-performance liquid chromatography-tandem mass spectrometry. The drug-drug effects of rhein on extracellular neurotransmitter efflux in the rat medial prefrontal cortex (mPFC) produced by clozapine were assayed by highperformance liquid chromatography-electrochemical detection. The results demonstrate that the clozapine PK was nonlinear. Pretreatment with rhein for 7 days increased the total blood concentration of clozapine, but significantly reduced the unbound clozapine concentrations in the mPFC by approximately 3-fold. Furthermore, 7 days of rhein pretreatment thoroughly abolished the efflux of dopamine and its metabolite (3,4-dihydroxyphenylacetic acid) and altered the profile of homovanillic acid, another metabolite of dopamine, in the mPFC. In conclusion, rhein was found to substantially decrease clozapine and norclozapine concentrations in the mPFC dialysate, and this is accompanied by lower concentrations in the neurotransmitters in the same biophase. These findings suggest that a detailed clinical study for drug-drug interactions is recommended.

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Section: Methodsmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

Hou

Lin

et al. 2015

J Pharmacol Exp Ther

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“…As DIA is metabolically transformed to Rh, only Rh has been quantified in biological fluids to evaluate its pharmacokinetics (Patel, Raval, & Pethani, 2020). Very few analytical methods have been reported for the analysis of Rh in biological matrices, including RP‐HPLC with various detection systems (Chakrabarty et al, 2008; Dan & Xinhui, 2003; Duan et al, 2013; Ojha et al, 2009; Tang et al, 2007; Yaroshenko et al, 2014), liquid chromatography–tandem mass spectrometry (Hou et al, 2014; Jiang et al, 2012; Layek et al, 2008; Lee et al, 2003; Lv et al, 2008; Yi et al, 2006) and RP‐HPLC with fluorescence detection (Mohammed et al, 2020; Wan et al, 2013; Zhang et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

RP‐HPLC method development, validation and pharmacokinetic applicability in preclinical evaluation of rhein treated with novel diacerein eutectics

Patel

Raval

Pethani

et al. 2022

Biomedical Chromatography

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The current study represents a bioanalytical method for the estimation of rhein (Rh, an active metabolite of diacerein, DIA) in rats treated with novel DIA eutectics to investigate the pharmacokinetics of DIA. A simple protein precipitation technique was used to extract Rh and the internal standard (IS), p-aminobenzoic acid, injected into a Phenomenex Gemini C 18 column. The separation was achieved by a gradient elution comprising ammonium acetate (10 mM; pH 3.0) and acetonitrile in an 18 min run time at a flow rate of 0.8 ml/min with retention times of 11.8 min (Rh) and 5.9 min (IS). The results revealed that the proposed method is linear over a range of 200-20,000 ng/ml (r 2 > 0.9988) of Rh and is precise and accurate. The method was fully validated as per the US Food and Drug Administration guidelines and a pharmacokinetic study in rats was performed for Rh following oral administration of the pure DIA and newly developed eutectics. Therefore, the present method could be used to estimate DIA to illustrate a comparative pharmacokinetic analysis. This can also be applied to its related multicomponent formulations for future studies.

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Probiotics decrease depressive behaviors induced by constipation via activating the AKT signaling pathway

Fan

Zhou

et al. 2018

Metab Brain Dis

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Chronic constipation is often accompanied by emotional disorders such as depression and anxiety. The aim of this study was to determine whether administration of a multispecies probiotic can decrease depressive behaviors through the gut-brain axis and identify any underlying mechanisms. A mouse model of constipation induced by loperamide (5 mg·kg,i.p.) was used. For that purpose, 36 ICR male mice were divided into three groups: control, constipation and probiotic groups. The probiotic group received treatment with a probiotic once per day for 14 days via a gavage. All other groups were given an equal volume of normal saline. The fecal parameters and intestinal transit ratio were recorded. The forced swimming test and tail suspension test were used to detect changes in depressive behaviors. Total superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) levels were measured by assay kits. We also detected neuronal survival, as well as phosphorylated Ser/Thr protein kinase (p-AKT), Bcl-2, Bcl-2 associated X protein (Bax) and cleaved caspase-3 levels in the hippocampus. The results showed that administration of a probiotic could ameliorate depressive behaviors and relieve neuronal cell injury in the hippocampal CA3 regions. Moreover, probiotic treatment decreased MDA levels and increased SOD activity. Furthermore, probiotic administration increased p-AKT and Bcl-2 levels in the hippocampus of the constipated mice, while decreasing the concentrations of Bax and cleaved caspase-3, so as to inhibit the neural apoptosis. In the present study, we confirm that probiotics can alleviate depression induced by constipation through protecting neuronal health via activation of the AKT signaling pathway.

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Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes

Cited by 14 publications

References 39 publications

The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis

RP‐HPLC method development, validation and pharmacokinetic applicability in preclinical evaluation of rhein treated with novel diacerein eutectics

Probiotics decrease depressive behaviors induced by constipation via activating the AKT signaling pathway

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