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Ruizhi Zhao - One of the best experts on this subject based on the ideXlab platform.
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clerosterol from vinegar baked Radix Bupleuri modifies drug transport
Oncotarget, 2017Co-Authors: Ya Zhao, Limin Feng, Xian Zhang, Ruizhi ZhaoAbstract:// Ya Zhao 1, 2, * , Li-Min Feng 1, * , Li-Juan Liu 1 , Xian Zhang 1 , Rui-Zhi Zhao 1 1 Department of Chinese Medicine Property Team, Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China 2 The Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China * These authors have contributed equally to this work Correspondence to: Rui-Zhi Zhao, email: 13610241754@163.com Keywords: clerosterol, transporter, Pgp, Mrp, Oct Received: August 04, 2016 Accepted: January 24, 2017 Published: February 09, 2017 ABSTRACT Vinegar-baked Radix Bupleuri (VBRB) is reportedly used to treat liver cancer when combined with traditional chemotherapy and data show that this combination may modify drug transport. We isolated clerosterol from VBRB and studied its effect on drug transporters in normal or transporter-overexpressing cells. Transporter activity was assayed using cellular substrate concentration and transporter expression with Western blot and RT-qPCR. Clerosterol decreased cisplatin uptake in BRL cells mainly through increasing Mrp2 gene expression. Clerosterol also decreased the uptake of colchicine in HEK 293 cells by increasing both Pgp and Mrp1 activity; in detail, it could increase Pgp protein but had marginal effects on Mrp1 protein and gene expression. Further study showed clerosterol increased OCT2 activity in HEK293-Pgp cells by increasing OCT2 protein and mRNA. Clerosterol could suppress Pgp overexpression but not by regulating protein and gene expression. And clerosterol had marginal effects on Mrp2 and Mrp1 activity in Mrp2- and Mrp1-overexpressing HEK293 cells. Thus, Clerosterol may be an active constituent of VBRB and may work against cancer multidrug resistance by inhibiting Pgp activity.
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vinegar amount in the process affected the components of vinegar baked Radix Bupleuri and its hepatoprotective effect
BMC Complementary and Alternative Medicine, 2016Co-Authors: Ya Zhao, Yinjie Wang, Ruizhi Zhao, Feijun XiangAbstract:Bupleuri Radix (in Chinese Chaihu), the dried roots of Bupleurum Chinense DC, is a traditional Chinese medicine widely used to treat fever, hepatitis, jaundice, nephritis, dizziness. When baked with vinegar, its effect is more focused on liver related disease. This paper was undertaken to determine the best vinegar amount in the processing and explore its key efficacy components. Hepatoprotective effects of Radix Bupleuri after processing with different amount of vinegar (1:5, 2:5, 3:5) were investigated on liver hurt rats, and the change of constituents were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). With the increasing amount of vinegar, the hepatoprotective effects of vinegar-baked Radix Bupleuri (VBRB) and the content of saikosaponin b2 increased. These results suggested that vinegar amount in the process affected the pharmacological effect of VBRB significantly and saikosaponin b2 may be the key efficacy component of it.
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vinegar baked Radix Bupleuri modulates the cell membrane constituents and inhibits the p gp activity in rat hepatocytes
BMC Complementary and Alternative Medicine, 2014Co-Authors: Ruizhi Zhao, Yinjie Wang, Zhicai XiaoAbstract:Vinegar-baked Radix Bupleuri (VBRB) enhances the effects of other drugs on the liver by increasing drug distribution to the liver, but the mechanism of action remains unclear. The present study was designed to determine the effects of VBRB on the membrane permeability, constituents, and P-glycoprotein (P-gp) activity of hepatocyte BRL cells, in order to interpret the liver targeting enhancing effects of VBRB. The membrane permeability and P-gp expression were analyzed by flow cytometry. The membrane constituents were determined by an automatic biochemistry analyzer and thin-layer chromatography. The results showed that, compared with the control, VBRB enhanced the membrane permeability by 41-67% (P < 0.05), which occurred in the absence of any cytotoxicity. VBRB had marginal effects on the cholesterol content, but significantly affected the total protein contents and the lipid constituents of the cell membrane in a dose- and time-dependent manner. VBRB inhibited P-gp expression in the cell membrane by 59-86% (P < 0.01). VBRB affects the constituents of BRL cells and increases its permeability, which may help explain its liver-targeting effects.
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modulatory effects of extracts of vinegar baked Radix Bupleuri and saikosaponins on the activity of cytochrome p450 enzymes in vitro
Xenobiotica, 2014Co-Authors: Tongya Yu, Yinjie Wang, Xianzhi Chen, Ruizhi ZhaoAbstract:Abstract1. In this article, the modulatory effects of extracts from vinegar-baked Radix Bupleuri (VBRB) and saikosaponins on the activity of CYP1A2, CYP2C9 and CYP3A4 were investigated in vitro.2. Microsomal in vitro incubation method was utilized to simulate metabolic reaction under physiological environment by incubating the marker with liver microsomes in the absence or presence of VBRB and saikosaponins. The contents of 4-acetamidophenol, 6β-hydroxyltestosterone and 4-hydroxydiclofenac, the metabolites of phenacetin, testosterone and diclofenac, which were selected as specific probe drugs of CYP1A2, CYP2C9 and CYP3A4, respectively, were analyzed by high-performance liquid chromatography.3. The production of the metabolites was incubation time dependent. The modulatory effects of different VBRB extracts and saikosaponins on CYP isoforms increased with concentration. Among all the extracts studied, BC1 has a strong inhibition effect compared to the three CYP isoforms tested, while the others have only s...
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liver targeting effect of vinegar baked Radix Bupleuri on oxymatrine in mice
Bioinformatics and Biomedicine, 2011Co-Authors: Ruizhi Zhao, You-jun ChenAbstract:In traditional Chinese medicine co-administration drugs with vinegar-baked Radix Bupleuri (VBRB) is usually used to increase the therapeutic effect in liver disease. However, the scientific data for this effect are not available. In this paper, effect of VBRB on the distribution of oxymatrine was studied. Mice were divided into four groups by random, oxymatrine control and oxymatrine co-administered with three different doses of VBRB. Concentrations of oxymatrine and its metabolite matrine in different tissues were determined by HPLC-MS. Target effencicy was evalutaed by AUC, Cmax, and Relative targeting efficiency (RTE). The results showed that compared to the control group, VBRB significantly increased the distribution of both oxymatrine and matrine in liver and meanwhile decreased their distribution in other tissues, indicating a strong liver targeting enhancing effect. The results of this paper implied that co-administration with VBRB may be a simple and efficiencient method for liver targeting therapy.
Zhenyu Li - One of the best experts on this subject based on the ideXlab platform.
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integrative hepatoprotective efficacy comparison of raw and vinegar baked Radix Bupleuri using nuclear magnetic resonance based metabolomics
Journal of Pharmaceutical and Biomedical Analysis, 2017Co-Authors: Jie Xing, Zhenyu LiAbstract:Abstract Radix Bupleuri (RB), with a Chinese name Chaihu, is one of the most popular Traditional Chinese herbal drug. It can be baked with vinegar to afford vinegar-baked Radix Bupleuri (VBRB), which is used in Traditional Chinese Medicine (TCM) for liver diseases treatment. In the present study, nuclear magnetic resonance-based metabolomic approach was used to compare the liver protective effect of RB and two types of VBRBs, which were prepared by two kinds of vinegar. The contents of 14 metabolites in the liver of carbon tetrachloride (CCl 4 ) treated mice were significantly altered in comparison with control group, and VBRB prepared by Shanxi vinegar showed best effect as revealed by the amount and regulatory degree of the perturbed metabolites. The metabolism pathways analysis showed that the liver protective effect was related with the energy metabolism, lipid metabolism, ketone body metabolism, glutathione metabolism, amino acids metabolism and nucleotide synthesis. The results presented here showed that metabolomic approach made it possible to disclose the subtle biological difference between two types of VBRB, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs.
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comparison of volatile components between raw and vinegar baked Radix Bupleuri by gc ms based metabolic fingerprinting approach
Evidence-based Complementary and Alternative Medicine, 2015Co-Authors: Jie Xing, Zhenyu LiAbstract:Radix Bupleuri (RB), also named Chaihu in Chinese, is a commonly used herbal drug in traditional Chinese medicine (TCM), and the processing of RB with vinegar to prepare vinegar-baked Radix Bupleuri (VBRB) has a long history in the clinic of TCM. In the present study, GC-MS coupled with multivariate data analysis was applied to compare the volatile components between crude and two vinegar processed RBs. After vinegar baking, the oil yields were decreased significantly, and the chemical compositions were also changed greatly. The chemical changes included the disappearance or appearance, as well as the content increase or decrease of some volatile compounds. The oil yields of two different VBRBs showed no significant difference but differed markedly in their chemical compositions, suggesting that the type of vinegar exerted great impacts on the vinegar-baking process. Thus, the effect of different vinegars on processing should be further investigated to ensure the therapeutic effect and safety of VBRB in clinic.
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chemical and biological comparison of raw and vinegar baked Radix Bupleuri
Journal of Ethnopharmacology, 2015Co-Authors: Zhenyu Li, Jie Xing, Guanhua DuAbstract:Abstract Ethnopharmacological relevance Radix Bupleuri (RB) is a commonly used herbal drug in Traditional Chinese Medicine (TCM), and it can be baked with vinegar to afford vinegar-baked Radix Bupleuri (VBRB), which is used in TCM for liver diseases treatment. In this study, the chemical compositions and biological effects between raw and two processed RBs by different vinegars were systematically compared. Materials and methods The chemical compositions of raw and two processed RBs were analyzed by 1 H NMR spectroscopy coupled with multivariate analysis. Two different extraction procedures were used, including direct extraction and liquid–liquid partition. Then HPLC was applied to determine the changes of saikosaponin contents. In addition, their liver protective effects against CCl 4 induced liver injury were also investigated, and the biochemical parameters and histopathology were measured after treatment of mice with raw RB and two processed RBs (5 g/kg/day) for 14 days. Results Multivariate analysis showed clear differences between the raw and the two processed RBs, and the vinegar-baking process induced elevated contents of ssb1, ssb2, acetic acid, malic acid, citric acid, 5-HMF, and ligustrazine, as well as the decreased contents of ssa, ssd, sucrose, glycine, succinic acid etc. In addition, both raw and processed RBs showed liver protective effects against CCl 4 induced liver injury, and the vinegar-baked RBs showed better effects than that of raw RB. Conclusions The raw and vinegar-baked RBs differed not only in the chemical compositions but also in the pharmacological effects. And two processed RBs also showed chemical differences, suggesting that the type of vinegar had an important effect on vinegar baking. In order to ensure the therapeutic effect and safety of TCM, the effect of different vinegars on processing of herbal drugs should be further studied.
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metabolic fingerprinting by 1hnmr for discrimination of the two species used as Radix Bupleuri
Planta Medica, 2012Co-Authors: Zhenyu Li, Jie Hu, Young Hae Choi, Robert VerpoorteAbstract:Radix Bupleuri is a traditional Chinese medicine harvested from two Bupleurum species ( B. chinense and B. scorzonerifolium ). It is widely used and is sourced from different regions of China. 1 H NMR spectroscopy and multivariate data analysis were applied to 67 Radix Bupleuri samples to discriminate the two species, and explore the influences of habitat and culture method on the quality of Radix Bupleuri based on their metabolomics profiles. Metabolites responsible for the differences between the two species were higher levels of arginine, citric acid, sucrose, saikosaponin b 1 /b 2 analogs, volatile oil with an ( E )-2-olefin aldehyde fragment, and fatty acids in B. scoreonerifolium , and more saikosaponin a/c/d analogs in B. chinense . The variances of two cultivation areas were observed due to the higher amount of saikosaponins a/c/d in samples from Shaanxi and lipidsin samples from Shanxi. No obvious difference was detected between cultivars and wild type. 1 HNMR metabolomics can simultaneously detect saikosaponins and hydrocarbon aldehydes, and also differentiate the two main saikosaponin skeletons, making it a suitable tool for the species discrimination and quality evaluation of Radix Bupleuri.
Hanhua Liang - One of the best experts on this subject based on the ideXlab platform.
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desirability function approach for the optimization of microwave assisted extraction of saikosaponins from Radix Bupleuri
Separation and Purification Technology, 2008Co-Authors: Zhuoyan Hu, Hanhua LiangAbstract:Microwave-assisted extraction (MAE) was applied to the extraction of saikosaponin a, c and d from Radix Bupleuri. Several operating parameters, namely microwave power, time, temperature and ethanol concentration, were optimized using response surface methodology (RSM) with a central composite rotatable design (CCRD). The ethanol concentration and time were found to be the most significant factors (p < 0.0001) for the extraction of all three saikosaponins. By using the desirability function approach, the optimum MAE conditions to obtain desirable extraction yields for all these saikosaponins simultaneously were found at the microwave power of 360–400 W, ethanol concentration of 47–50%, temperature of 73–74 °C and time of 5.8–6.0 min. At these conditions, the yields from the verification experiments were 96.18–96.91% for saikosaponin a, 95.05–95.71% for saikosaponin c and 97.05–97.25% for saikosaponin d, which were in good agreement with the predicted values.
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investigation on ultrasound assisted extraction of saikosaponins from Radix Bupleuri
Separation and Purification Technology, 2007Co-Authors: Shuna Zhao, Kinchor Kwok, Hanhua LiangAbstract:Ultrasound assisted extraction (UAE) of saikosaponins from Radix Bupleuri (Bupleurum Chinense DC) was studied. The effects of various factors such as time (t), temperature (T), ultrasound power (I), particle size (S), solvent to solid ratio (R) and solvent concentration (C) on the yield of target components were investigated. The experimental results indicated that the extraction by UAE is six times faster than those by conventional thermal extraction. It is also found that fast extraction rate was obtained in the first 30 min of sonication. Prolonged sonication did not give a proportional increase in the yield. For the effect of ultrasound power, the maximum yield was obtained at the power level of around 21 W. Scanning electron microscope (SEM) images of the plant cells after UAE treatment were obtained to provide visual evidence of the sonication effect. The effects of particle size, solvent to solid ratio and solvent concentration on the yield are also discussed. The preliminary optimum conditions for UAE of saikosaponins were found at time of 30 min, temperature of 80 °C, power of 21 W, particle size <0.3 mm, solvent to solid ratio of 25 ml/g and solvent concentration of 50%.
Xin-guo Jiang - One of the best experts on this subject based on the ideXlab platform.
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preparation of nasal temperature sensitive in situ gel of Radix Bupleuri and evaluation of the febrile response mechanism
Drug Development and Industrial Pharmacy, 2010Co-Authors: En Chen, Qi-zhi Zhang, Jun Chen, Xin-guo JiangAbstract:Objective: This study developed a nasal temperature-sensitive in situ gel system for Radix Bupleuri. Method: Using 20% Poloxamer 407 as the gel base and 6% PEG 4000 adjusting the gelation temperature. Results: The system is liquid at 4°C. It can change its phase to gel above 30°C, which is close to the temperature in nasal cavity. The antipyretic effect produced by Radix Bupleuri in situ gel formulation was investigated in fevered rabbits. The results show that it can prolong the effective time to 24 hours compared with 4–6 hours in Radix Bupleuri intranasal solution. The antipyretic response mechanism was researched by evaluating the relationship between body temperature and concentrations of cyclic adenosine monophosphate in cerebrospinal fluid. The results showed that the two parameters were positively correlated (r = 0.9435, P < 0.05). Six hours later after given in situ gel, the concentrations of cAMP were significantly lower than those in the solution group. It confirmed that temperature-sensitive R...
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A novel nasal delivery system of a chinese traditional medicine,Radix Bupleuri, based on the concept of ion-activated in situ gel
Archives of Pharmacal Research, 2007Co-Authors: En Chen, Qi-zhi Zhang, Xin-guo JiangAbstract:The purpose of this study was to develop a nasal in situ gel system for Radix Bupleuri employing gellan gum as a polymer. Radix Bupleuri in situ gel containing 0.2 mL essential oil extracted from 450 g Radix Bupleuri , proper solubilizing agents and gellan gum (0.5% w/v) was prepared and characterized. The antipyretic effect produced by in situ gel formulation was investigated in fevered rabbits and compared to an intranasal solution. The resulting in situ gel was a clear and light-yellow liquid, with viscosity of 346 mPa.s and caproic acid content of 1.31± 0.01 mg/mL Intranasal administration of this preparation to fevered rabbits decreased body temperature markedly (1.1°C at the doses of oil from 1.5 g Bupleuri/body) and the effect could last for 20-30 h. The results suggest that Radix Bupleuri in situ gel can be greater effective than the solution in the treatment of fever.
En Chen - One of the best experts on this subject based on the ideXlab platform.
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preparation of nasal temperature sensitive in situ gel of Radix Bupleuri and evaluation of the febrile response mechanism
Drug Development and Industrial Pharmacy, 2010Co-Authors: En Chen, Qi-zhi Zhang, Jun Chen, Xin-guo JiangAbstract:Objective: This study developed a nasal temperature-sensitive in situ gel system for Radix Bupleuri. Method: Using 20% Poloxamer 407 as the gel base and 6% PEG 4000 adjusting the gelation temperature. Results: The system is liquid at 4°C. It can change its phase to gel above 30°C, which is close to the temperature in nasal cavity. The antipyretic effect produced by Radix Bupleuri in situ gel formulation was investigated in fevered rabbits. The results show that it can prolong the effective time to 24 hours compared with 4–6 hours in Radix Bupleuri intranasal solution. The antipyretic response mechanism was researched by evaluating the relationship between body temperature and concentrations of cyclic adenosine monophosphate in cerebrospinal fluid. The results showed that the two parameters were positively correlated (r = 0.9435, P < 0.05). Six hours later after given in situ gel, the concentrations of cAMP were significantly lower than those in the solution group. It confirmed that temperature-sensitive R...
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A novel nasal delivery system of a chinese traditional medicine,Radix Bupleuri, based on the concept of ion-activated in situ gel
Archives of Pharmacal Research, 2007Co-Authors: En Chen, Qi-zhi Zhang, Xin-guo JiangAbstract:The purpose of this study was to develop a nasal in situ gel system for Radix Bupleuri employing gellan gum as a polymer. Radix Bupleuri in situ gel containing 0.2 mL essential oil extracted from 450 g Radix Bupleuri , proper solubilizing agents and gellan gum (0.5% w/v) was prepared and characterized. The antipyretic effect produced by in situ gel formulation was investigated in fevered rabbits and compared to an intranasal solution. The resulting in situ gel was a clear and light-yellow liquid, with viscosity of 346 mPa.s and caproic acid content of 1.31± 0.01 mg/mL Intranasal administration of this preparation to fevered rabbits decreased body temperature markedly (1.1°C at the doses of oil from 1.5 g Bupleuri/body) and the effect could last for 20-30 h. The results suggest that Radix Bupleuri in situ gel can be greater effective than the solution in the treatment of fever.