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Dong Liu - One of the best experts on this subject based on the ideXlab platform.
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mechanism of Calculus Bovis sativus in inhibiting hepatocyte lipid deposition based on serum pharmacology
China journal of Chinese materia medica, 2019Co-Authors: Chengliang Zhang, Xiuhua Ren, Dong Xiang, Jinyu Yang, Dong LiuAbstract:The aim of this paper was to investigate the molecular mechanism of Calculus Bovis Sativus( CBS) in alleviating lipid accumulation in vitro by serum pharmacology. The CBS-containing serum of mice was obtained by serum pharmacology method to evaluate its effect on the proliferation of LO2 hepatocytes. The lipid reducing effects of CBS-containing serum through Nrf2 was evaluated by fructose-induced LO2 hepatocyte steatosis model,nuclear factor erythroid 2 related factor 2( Nrf2) agonist oltipraz combined intervention,cell oil red O staining and intracellular triglyceride( TG) content. The effects of CBS-containing serum on lipid peroxidation and hepatocytes apoptosis were evaluated by reactive oxygen species( ROS) and apoptosis assay,respectively. Real-time quantitative polymerase chain reaction( PCR) was used to detect the relative expression of lipid synthesis-related genes and apoptosis-related genes.RESULTS:: showed that CBS drug-containing serum had no significant effect on LO2 hepatocyte proliferation. As compared with the model group,CBS-containing serum could effectively reduce the formation of lipid droplets in fructose-induced LO2 hepatocytes,significantly reduce intracellular TG and ROS levels,and significantly reduce hepatocyte apoptosis rate( P < 0. 05). As compared with the model group,carbohydrate responsive element binding protein( ChREBP),sterol regulatory element binding protein-1 c( SREBP-1 c),fatty acid synthase( FAS),acetyl-CoA carboxylase 1( ACC1),stearoyl-CoA desaturase 1( SCD1),Bax and caspase-3 mRNA levels were significantly reduced in CBS drug-containing serum treatment group( P<0. 05). All of the above effects could be reversed by oltipraz.In conclusion,CBS-containing serum can significantly inhibit the fructose-induced LO2 liver fat deposition,and the mechanism may be related to reducing intracellular ROS level through the Nrf2 pathway and improving intracellular peroxidation state to reduce apoptosis.
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Calculus Bovis sativus up regulates hepatic protein 2 mrp2 and mrp4 in 17α ethynylestradiol induced cholestasis via a regulatory effect on er signaling
Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan, 2019Co-Authors: Hongping Song, Dong LiuAbstract:Objective To investigate the pathway through which Calculus Bovis Sativus (CBS) up-regulates hepatic multidrug resistance-associated protein 2 (Mrp2) and Mrp4 in 17α-ethynylestradiol (EE)-induced cholestasis. Methods Five groups of rats were designed: control group, EE+ICI182780 group, EE group, EE+CBS 50 mg/kg group and EE + CBS 150 mg/kg group. CBS (50 and 150 mg·kg－1·d－1 ) was orally given to rats by gavage for five consecutive days in coadministration with EE. The levels of cholestasis biomarkers, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL) were determined by biochemical methods. The bile flow was measured. The histopathology of the liver tissue was evaluated. The expression of Mrp2, Mrp3, Mrp4, estrogen receptor α (ERα) and ERs was determined by Western blotting. Results CBS markedly improved EE-induced cholestasis. EE exposure significantly reduced hepatic Mrp2 and Mrp4 expression compared with the control group. EE also dramatically up-regulated the expression of Mrp3. Compared to the EE group, CBS notably up-regulated hepatic Mrp2 and Mrp4 but failed to influence the Mrp3 level significantly. ICI182780, an ER antagonist, showed similar beneficial effects as CBS. Decreased expression of Mrp2 and Mrp4 caused by EE was also restored by ICI182780. Additionally, EE significantly induced he- patic ERα expression, which was reversed by ICI182780 or CBS (150 mg/kg) treatment, suggesting that CBS exerted a moderate regulatory effect on ER signaling. Conclusion CBS up-regulated hepatic Mrp2 and Mrp4 expression in EE-induced cholestasis, which might be associated with its regulation of ER signaling.
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Calculus Bovis Sativus Improves Bile Acid Homeostasis via Farnesoid X Receptor-Mediated Signaling in Rats With Estrogen-Induced Cholestasis
Frontiers Media S.A., 2019Co-Authors: Dong Xiang, Yanan Liu, Jinyu Yang, Si Zhang, Chenliang Zhang, Dong LiuAbstract:Cholestatic diseases are characterized by toxic bile acid (BA) accumulation, and abnormal BA composition, which subsequently lead to liver injury. Biochemical synthetic Calculus Bovis Sativus (CBS) is derived from natural Calculus Bovis, a traditional Chinese medicine, which has been used to treat hepatic diseases for thousands of years. Although it has been shown that CBS administration to 17α-ethinylestradiol (EE)-induced cholestatic rats improves bile flow and liver injury, the involved underlying mechanism is largely unknown. In this study, we showed that CBS administration to EE-induced cholestatic rats significantly decreased serum and hepatic BA levels and reversed hepatic BA composition. DNA microarray analysis suggested that the critical pathways enriched by CBS treatment were bile secretion and primary BA synthesis. These findings led us to focus on the effects of CBS on regulating BA homeostasis, including BA transport, synthesis and metabolism. CBS enhanced hepatic BA secretion by inducing efflux transporter expression and inhibiting uptake transporter expression. Moreover, CBS reduced BA synthesis by repressing the expression of BA synthetic enzymes, CYP7A1 and CYP8B1, and increased BA metabolism by inducing the expression of metabolic enzymes, CYP3A2, CYP2B10, and SULT2A1. Mechanistic studies indicated that CBS increased protein expression and nuclear translocation of hepatic and intestinal farnesoid X receptor (FXR) to regulate the expression of these transporters and enzymes. We further demonstrated that beneficial effects of CBS administration on EE-induced cholestatic rats were significantly blocked by guggulsterone, a FXR antagonist. Therefore, CBS improved BA homeostasis through FXR-mediated signaling in estrogen-induced cholestatic rats. Together, these findings suggested that CBS might be a novel and potentially effective drug for the treatment of cholestasis
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Data_Sheet_1_Calculus Bovis Sativus Improves Bile Acid Homeostasis via Farnesoid X Receptor-Mediated Signaling in Rats With Estrogen-Induced Cholestasis.pdf
2019Co-Authors: Dong Xiang, Yanan Liu, Jinyu Yang, Si Zhang, Chenliang Zhang, Dong LiuAbstract:Cholestatic diseases are characterized by toxic bile acid (BA) accumulation, and abnormal BA composition, which subsequently lead to liver injury. Biochemical synthetic Calculus Bovis Sativus (CBS) is derived from natural Calculus Bovis, a traditional Chinese medicine, which has been used to treat hepatic diseases for thousands of years. Although it has been shown that CBS administration to 17α-ethinylestradiol (EE)-induced cholestatic rats improves bile flow and liver injury, the involved underlying mechanism is largely unknown. In this study, we showed that CBS administration to EE-induced cholestatic rats significantly decreased serum and hepatic BA levels and reversed hepatic BA composition. DNA microarray analysis suggested that the critical pathways enriched by CBS treatment were bile secretion and primary BA synthesis. These findings led us to focus on the effects of CBS on regulating BA homeostasis, including BA transport, synthesis and metabolism. CBS enhanced hepatic BA secretion by inducing efflux transporter expression and inhibiting uptake transporter expression. Moreover, CBS reduced BA synthesis by repressing the expression of BA synthetic enzymes, CYP7A1 and CYP8B1, and increased BA metabolism by inducing the expression of metabolic enzymes, CYP3A2, CYP2B10, and SULT2A1. Mechanistic studies indicated that CBS increased protein expression and nuclear translocation of hepatic and intestinal farnesoid X receptor (FXR) to regulate the expression of these transporters and enzymes. We further demonstrated that beneficial effects of CBS administration on EE-induced cholestatic rats were significantly blocked by guggulsterone, a FXR antagonist. Therefore, CBS improved BA homeostasis through FXR-mediated signaling in estrogen-induced cholestatic rats. Together, these findings suggested that CBS might be a novel and potentially effective drug for the treatment of cholestasis.
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investigation of the synergistic effects of haloperidol combined with Calculus Bovis sativus in treating mk 801 induced schizophrenia in rats
Experimental Animals, 2017Co-Authors: Kai Lei, Chengliang Zhang, Yanan Liu, Xiuhua Ren, Dong LiuAbstract:Clinical studies that focused on treating schizophrenia showed that Calculus Bovis Sativus (CBS), a substitute of Calculus Bovis, when used in combination with haloperidol could significantly lower the dosage of haloperidol compared with treatment with haloperidol alone, whereas efficacy was maintained. The aim of this study was to investigate the synergetic anti-schizophrenia effects in rats using CBS in combination with haloperidol. An open field test was conducted to verify the pharmacodynamic effects of a combination treatment of CBS and haloperidol on MK-801-induced schizophrenic rats. Rat plasma concentrations of intragastric haloperidol and intravenous haloperidol were determined after oral administration of a single dose or 1-week of pretreatment with CBS (50 mg/kg). The pharmacodynamic data showed a significant decrease in locomotor activity and an increase in the percentage of the central distance when haloperidol was concomitantly administered with CBS compared with haloperidol administration alone. The AUC0-∞ and Cmax of haloperidol in the orally coadministered groups were significantly higher compared with the oral treatment with haloperidol alone. In conclusion, oral coadministration of CBS with haloperidol resulted in a synergistic effect in rats. The enhanced oral bioavailability of haloperidol when combined with CBS might be attributed to the interaction between them.
Jia-yi Kan - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the effect of Bovis Calculus artifactus on eight rat liver cytochrome p450 isozymes using lc ms ms and cocktail approach
Xenobiotica, 2021Co-Authors: Yun-jing Zhang, Can Peng, Wen-li Zhou, Qian Wang, Jia-yi KanAbstract:Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach.Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme.The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine.
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Evaluation of the effect of Bovis Calculus Artifactus on eight rat liver cytochrome P450 isozymes using LC-MS/MS and cocktail approach
2021Co-Authors: Yun-jing Zhang, Can Peng, Wen-li Zhou, Qian Wang, Jia-yi KanAbstract:Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach.Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme.The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p p > 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine. Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach. Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme. The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p p > 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine.
Can Peng - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the effect of Bovis Calculus artifactus on eight rat liver cytochrome p450 isozymes using lc ms ms and cocktail approach
Xenobiotica, 2021Co-Authors: Yun-jing Zhang, Can Peng, Wen-li Zhou, Qian Wang, Jia-yi KanAbstract:Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach.Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme.The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine.
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Evaluation of the effect of Bovis Calculus Artifactus on eight rat liver cytochrome P450 isozymes using LC-MS/MS and cocktail approach
2021Co-Authors: Yun-jing Zhang, Can Peng, Wen-li Zhou, Qian Wang, Jia-yi KanAbstract:Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach.Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme.The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p p > 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine. Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach. Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme. The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p p > 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine.
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development and validation of a sensitive lc ms ms method for the simultaneous determination of multicomponent contents in artificial Calculus Bovis
Journal of Chromatographic Science, 2014Co-Authors: Can Peng, Jixin Tian, Yin Huang, Yuan Tian, Zunjian ZhangAbstract:Artificial Calculus Bovis is a major substitute in clinical treatment for Niuhuang, a widely used, efficacious but rare traditional Chinese medicine. However, its chemical structures and the physicochemical properties of its components are complicated, which causes difficulty in establishing a set of effective and comprehensive methods for its identification and quality control. In this study, a simple, sensitive and reliable liquid chromatography-tandem mass spectrometry method was successfully developed and validated for the simultaneous determination of bilirubin, taurine and major bile acids (including six unconjugated bile acids, two glycine-conjugated bile acids and three taurine-conjugated bile acids) in artificial Calculus Bovis using a Zorbax SB-C18 column with a gradient elution of methanol and 10 mmol/L ammonium acetate in aqueous solution (adjusted to pH 3.0 with formic acid). The mass spectra were obtained in the negative ion mode using dehydrocholic acid as the internal standard. The content of each analyte in artificial Calculus Bovis was determined by monitoring specific ion pairs in the selected reaction monitoring mode. All analytes demonstrated perfect linearity (r(2) > 0.994) in a wide dynamic range, and 10 batches of samples from different sources were further analyzed. This study provided a comprehensive method for the quality control of artificial Calculus Bovis.
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herb drug pharmacokinetic interaction of artificial Calculus Bovis with diclofenac sodium and chlorpheniramine maleate in rats
Journal of Pharmacy and Pharmacology, 2013Co-Authors: Can Peng, Jixin Tian, Yin Huang, Yuan Tian, Zunjian ZhangAbstract:Objectives To investigate the herb–drug pharmacokinetic interaction of artificial Calculus Bovis (ACB) with diclofenac sodium (DS) and chlorpheniramine maleate (CPM) in rats. Methods A sensitive high-performance liquid chromatography coupled with tandem mass spectrometry method was developed and validated for the simultaneous determination of DS and CPM in rat plasma. The proposed method was successfully applied to compare the herb–drug pharmacokinetic interaction of ACB with DS and CPM in rats following intragastric administration. Key findings The proposed method had good linearity and no endogenous material interfered with the analytes and internal standard peaks. The lower limit of quantification of DS and CPM was 1 and 0.1 ng/ml, respectively. There was no apparent pharmacokinetic interaction between DS and CPM. Co-administration of ACB with DS noticeably increased the area under the concentration–time curve (AUC0-∞) and peak plasma concentration (Cmax) of DS, while the parameters time of peak concentration (Tmax), clearance (ClZ/F) and apparent volume of distribution (VZ/F) of DS significantly decreased. Meanwhile, co-administration of ACB with CPM noticeably increased the Tmax, ClZ/F and VZ/F of CPM. A marked decline in AUC0-∞ and Cmax of CPM occurred in the presence of ACB. Conclusions This study indicated that co-administration of ACB with DS and CPM can result in an apparent herb–drug pharmacokinetic interaction in rats.
Hongjiao Cai - One of the best experts on this subject based on the ideXlab platform.
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upregulation of pdzk1 by Calculus Bovis sativus may play an important role in restoring biliary transport function in intrahepatic cholestasis
Evidence-based Complementary and Alternative Medicine, 2017Co-Authors: Dong Xiang, Chengliang Zhang, Hongjiao Cai, Kai Lei, Chengyang Feng, Dong LiuAbstract:Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS) can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) in 17α-ethynylestradiol- (EE-) induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP. Intrahepatic cholestasis model was induced in rats with injection of EE for five consecutive days and then the biliary excretion rates and cumulative biliary excretions were measured. The mRNA and protein expression levels of PDZK1 were detected by reverse transcription-quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analysis. When treated with CBS, cumulative biliary excretions and mRNA and protein expressions of PDZK1 were significantly increased in intrahepatic cholestasis rats. This study demonstrated that CBS exerted a beneficial effect on EE-induced intrahepatic cholestasis rats by restoring biliary transport function, which may result from the upregulation of PDZK1 expression.
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preparation in vitro and in vivo evaluations of compound Calculus Bovis sativus and ornidazole film
Biological & Pharmaceutical Bulletin, 2016Co-Authors: Ping Gao, Hongjiao Cai, Chengliang Zhang, Ying Chen, Dong LiuAbstract:The aim of this study was to develop and to investigate a film of compound Calculus Bovis Sativus (CBS) and ornidazole film. A uniform mucoadhesive film was herein successfully obtained by a film-forming solusion containing insoluable drug. This film, as a valid adjunct for the treatment of oral mucosal ulcer, consisted of two main drugs (CBS, ornidazole) and three polymers (hydroxypropyl methyl cellulose, chitosan, poly(vinyl alcohol) (PVA)). The film was prepared with the film-forming suspension, using casting-solvent evaporation technique. The drug content, release behavior, swelling index and mucoadhesive properties of the film were detected. Then the effects of the prepared film on a glacial acetic acid-induced oral mucosal ulceration model of rabbits were evaluated. Moreover, the in vivo release of bilirubin and ornidazole in saliva were also detected in the oral mucosae of healthy volunteers. The films showed favorable in vitro drug release behaviors and swelling properties. Mucosal wounds in the animals were significantly relieved. With the films well tolerated, the salivary concentrations of ornidazole were maintained above the minimum inhibitory concentration against CBS for about 2 h. The compound CBS and ornidazole film functioned better than the film only containing CBS and ornidazole did. Therefore, it is a potentially efficient drug delivery system for the treatment of oral ulcers.
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development of a rapid and simple lc ms ms method for identification and quality control of natural Calculus Bovis and Calculus Bovis sativus
Analytical Methods, 2015Co-Authors: Chengyang Feng, Hongjiao Cai, Chengliang Zhang, Dong LiuAbstract:Calculus Bovis sativus (C. Bovis sativus, CBS), with the same pharmacodynamics activities as those of natural C. Bovis (CB), has been approved as an ideal substitute in China. However, in the latest edition of the Chinese Pharmacopoeia, only cholic acid and bilirubin are used as the markers for quality control. To overcome current limitations and to further improve its quality control method, a rapid and reliable method was herein developed for simultaneous qualitative and quantitative analyses of taurine and twelve bile acids (BAs) in natural CB and CBS by liquid chromatography coupled with tandem mass spectrometry. Taurine and BAs were separated using a Diamonsil C18 column (150 mm × 2.1 mm i.d., 5 μm) with acetonitrile: water containing 10 mM ammonium acetate (pH 3) as mobile phase in a gradient elution program. Mass spectra were obtained in the negative ion mode through multiple reaction monitoring of respective mass transitions. This method had satisfactory separation efficiency, high sensitivity, little potential interference, and short running time. The average recoveries ranged from 93.0% to 107.3%, with relative standard deviations of less than 9.0% for all thirteen analytes of interest. Taurine and characteristic BAs, especially conjugated BAs, may partially reflect the internal quality of CBS and natural CB. Combining the ratios of cholic acid/deoxycholic acid and unconjugated BAs/conjugated BAs with quantitative data of single BA and chromatographic profiles may be able to control the quality of CBS. In conclusion, this method can be used for explicit identification and quality control of CBS and natural CB.
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beneficial effect of Calculus Bovis sativus on 17α ethynylestradiol induced cholestasis in the rat
Life Sciences, 2014Co-Authors: Dong Liu, Mujun Chang, Chengliang Zhang, Hongjiao CaiAbstract:Abstract Aims Calculus Bovis Sativus (CBS) shares similar pharmacological effects with Calculus Bovis like relieving hepatobiliary diseases. This study aims to investigate the effect and mechanism of CBS on 17α-ethynylestradiol (EE)-induced cholestasis in the rat. Main methods CBS (50 and 150 mg/kg per day) was intragastrically (i. g.) given to experimental rats for 5 consecutive days in coadministration with EE. The levels of serum biomarkers, hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined by biochemical methods. The bile flow in 2 h was measured. The histopathology of the liver tissue was evaluated. The expression of transporter was studied by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. Key findings CBS treatment significantly prevented EE-induced increases in serum levels of biomarkers. Decreased bile flow by EE was restored with CBS treatment. The tissue lesions were also relieved with CBS treatment. Western blot studies indicated that EE significantly decreased the protein expression of multidrug resistance-associated protein 2 (Mrp2) and breast cancer resistance protein (Bcrp), but notably increased P-glycoprotein (P-gp) protein, compared with the control group. CBS treatment significantly increased the protein expression of P-gp, Mrp2 and Bcrp compared with the EE group. RT-qPCR studies indicated that EE down-regulated Bcrp at transcriptional level. CBS up-regulated the mRNA expression of P-gp, Mrp2 and Bcrp compared with the EE group. Significance The present study indicated that CBS exerted a beneficial effect on EE-induced cholestasis in the rat, which may result from its induction of P-gp, Mrp2 and Bcrp expression.
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effects of in vitro cultivated Calculus Bovis compound on pulmonary lesions in rabbits with schistosomiasis
World Journal of Gastroenterology, 2010Co-Authors: Zhen Yang, Hongjiao Cai, Liwei Song, Zheng ZhouAbstract:AIM: To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation (ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. METHODS: The experimental group included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco. The control group included 20 portal hypertensive rabbits with schistosomiasis treated by praziquantel. The morphological changes of the pulmonary tissues were observed under light and electron microscopy. The expression of fibronectin (FN) and laminin (LN) in the lung tissues was analyzed by immunohistochemistry. RESULTS: Under light microscope, the alveolar exudation in the lung tissue was more frequently observed in the control group, while the alveolar space was fairly dry in the lung tissue of ICCBco group. Under electron microscope, more alveolar exudation in the lung tissue, and more macrophages, alveolar angiotelectasis and the blurred three-tier structure of alveolar-capillary barrier could be seen in the control group. In ICCBco group, fibers within the alveolar interspace slightly increased in some lung regions, and the structure of type I epithelium, basement membrane and endodermis was complete, and no obvious exudation from the alveolar space, and novascular congestion could be observed. There was a positive or strong positive expression of FN and LN in the lung tissue of the control group, while there was a negative or weak positive expression of FN and LN in ICCBco group. CONCLUSION: ICCBco can effectively prevent pulmonary complications in portal hypertensive rabbits with schistosomiasis by means of improving lung microcirculation and lowering the content of extracellular matrix.
Yun-jing Zhang - One of the best experts on this subject based on the ideXlab platform.
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evaluation of the effect of Bovis Calculus artifactus on eight rat liver cytochrome p450 isozymes using lc ms ms and cocktail approach
Xenobiotica, 2021Co-Authors: Yun-jing Zhang, Can Peng, Wen-li Zhou, Qian Wang, Jia-yi KanAbstract:Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach.Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme.The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine.
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Evaluation of the effect of Bovis Calculus Artifactus on eight rat liver cytochrome P450 isozymes using LC-MS/MS and cocktail approach
2021Co-Authors: Yun-jing Zhang, Can Peng, Wen-li Zhou, Qian Wang, Jia-yi KanAbstract:Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach.Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme.The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p p > 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine. Bovis Calculus Artifactus (BCA) is the main substitute for natural Calculus Bovis, a traditional drug in China used to treat high fever, convulsion, and sore throat. The effect of BCA on cytochrome P450 (CYP) activities is unknown. This study was to investigate the effect of BCA on eight rat hepatic microsomal CYPisozymes to evaluate the potential drug interactions using the cocktail approach. Metabolites of the eight isoform probe substrates of CYP isozymes were quantified by LC-MS/MS. The method was validated by incubating known CYP inhibitors α-naphthoflavone (CYP1A2), thiotepa (CYP2B1), quercetin (CYP2C7), sulfaphenazole (CYP2C6), ticlopidine (CYP2C11), quinidine (CYP2D1), ketoconazole (CYP3A1),4-methylpyrazole (CYP2E1) with individual probe substrate and rat liver microsomes. The formation rates of the corresponding metabolites of the eight probe substrates were determined to evaluate the activity of each isozyme. The results showed that BCA has different degrees of inhibitory effect on four CYP450 isoforms (CYP2C6, CYP2C11, CYP2D1, CYP3A1) (p p > 0.05). Attention should be paid to the BCA-drug interactions by careful monitoring and appropriate dosage adjustments in the concurrent use of the drugs which are metabolized by CYP1A2, CYP2C19, and CYP3A4. Abbreviations: BCA, Bovis Calculus artifactus; CYP, cytochrome P450; DDIs, drug-drug interactions; ESI, electrospray ionization; MRM, multiple reaction monitoring; NBC, Natural Bovis Calculus; QC, quality control; T CM, traditional Chinese medicine.
