Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell e...Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.展开更多
A simple, sensitive and specific high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）method combined with solid phase extraction has been developed and validated for the simultaneous quantifi...A simple, sensitive and specific high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）method combined with solid phase extraction has been developed and validated for the simultaneous quantification of paeoniflorinand albiflorin in rats plasma and tissue homogenate after administration of total glycosides of paeony （TGP）. Chromatographicseparation was achieved on a C15 column （150 mmx4.6 mm, 5 pro） with mobile phase consisted of acetonitrile-0.05% formicacid aqueous （20： 80, v/v） at a flow rate of 0.5 mL/min. The analytes were detected with triple-quadrupole mass spectrometer usingturbo ion spray with negative ionization in the multiple reaction-monitoring （MRM） modes. The results of method validationconformed to the requirements for the determination of biological samples. This method was successfully applied to thepharmacokinetics and tissue distribution study of TGP in rats. The results showed that paeonifiorin and albiflorin wereabsorbed and reached peak value quickly, and had the similar pharmacokinetic characteristics. Both of them underwent a rapid andwide distribution in the tissues throughout the whole body, among which stomach was the main distribution tissue. Moreover, theyhad the ability to cross the blood-brain barrier.展开更多
Objective: To summarize the evidence from systematic reviews(SRs) on the benefits and safety of Tripterygium glycosides(TG) and total glucosides of paeony(TGP), commonly used to treat rheumatoid arthritis(RA) in China...Objective: To summarize the evidence from systematic reviews(SRs) on the benefits and safety of Tripterygium glycosides(TG) and total glucosides of paeony(TGP), commonly used to treat rheumatoid arthritis(RA) in China, for patients with RA. Methods: SRs of randomized controlled trials(RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach. Results: Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology(ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from "low" to "moderate". Conclusions: TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients.展开更多
Total paeony glycoside（TPG） is obtained from Radix Paeoniae Rubra with a variety of bioactivities. However, the low solubility and bioavailability limit its application. The present study aimed to develop TPG nanocr...Total paeony glycoside（TPG） is obtained from Radix Paeoniae Rubra with a variety of bioactivities. However, the low solubility and bioavailability limit its application. The present study aimed to develop TPG nanocrystals to increase the dissolution and then improve the oral bioavailability. TPG nanocrystals were prepared via precipitation and high-pressure homogenization method. The physical-chemical properties of the optimal TPG nanocrystals in terms of particle size, zeta potential, morphology and crystallinity were evaluated. The results showed that TPG nanocrystals had a mean particle size of（210.2±2.5） nm, a polydispersity index of 0.191±0.033 and a zeta potential of（–22.4±1.2） mV. The result of differential scanning calorimetry showed that the nanocrystals were still in crystalline state after the preparation procedure. Transmission electron microscopy（TEM） results showed that the nanosuspension was in spherical shape. The pharmacokinetics of TPG nanocrystals for rats was investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. Compared with the TPG coarse suspension, TPG nanocrystals exhibited significant increase in AUC0–∞（approximately 1.85-fold）. Taken together, TPG nanocrystals could be used as a promising drug delivery system due to the enhanced oral bioavailability of TPG.展开更多
目的:研究赤芍总苷对肺癌模型大鼠抑癌相关基因表达的影响。方法:将90只大鼠随机分为正常组、模型组、阳性对照组[环磷酰胺,50 mg/(kg·d)]和赤芍总苷低、中、高剂量组[50、100、200 mg/(kg·d)],每组15只。除正常组外,其余各...目的:研究赤芍总苷对肺癌模型大鼠抑癌相关基因表达的影响。方法:将90只大鼠随机分为正常组、模型组、阳性对照组[环磷酰胺,50 mg/(kg·d)]和赤芍总苷低、中、高剂量组[50、100、200 mg/(kg·d)],每组15只。除正常组外,其余各组大鼠均采用左肺叶支气管内一次性灌注致癌碘油液复制肺癌模型,造模成功后,每周周一至周五各组大鼠于背iv相应药物,正常组和模型组iv等体积生理盐水,连续16周。采用逆转录-聚合酶链反应法测定大鼠肺组织中多药耐药相关蛋白(MRP)、人多药耐药基因(MDR1)和凋亡相关基因P21、P16 m RNA的表达;采用免疫组化法测定肺组织中抑癌基因P53蛋白的表达,计算其阳性率;观察肺组织病理变化。结果:与正常组比较,模型组大鼠肺组织中MRP、MDR1、P21、P16 m RNA及P53蛋白表达(阳性率为66.67%)水平明显升高(P<0.05);与模型组比较,阳性对照组和赤芍总苷低、中、高剂量组大鼠肺组织中MRP、MDR1、P21、P16 m RNA及P53蛋白表达(阳性率分别为46.67%、46.67%、40.00%、13.33%)水平降低并呈剂量依赖性,且赤芍总苷中、高剂量组比阳性对照组降低程度更显著(P<0.05);赤芍总苷各剂量组间比较,各指标差异均有统计学意义(P<0.05)。结论:赤芍总苷可明显抑制肺癌模型大鼠MRP、MDR1、P21、P16基因及P53蛋白的表达。展开更多
基金supported by the National Natural Science Foundation of China(82074036).
文摘Objective:To explore and validate the potential targets of Paeoniae Radix Alba(P.Radix,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell experiments.Methods:Network pharmacology was used to identify the common potential targets of P.Radix and chemical liver injury.Molecular docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1.The cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of P.Radix,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western blot.Results:Analysis through network pharmacology revealed 13 key compounds of P.Radix,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and CASP3.Gene Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation.Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and CASP3.Different concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 cells.Conclusion:P.Radix primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,CASP3.TGP,the main active compound of P.Radix,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.
基金Natural Science Foundation of Hebei Province of China(Grant No.C2011206158,08B031)Hundreds of Innovative Talents Project of Hebei Education Department of China
文摘A simple, sensitive and specific high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）method combined with solid phase extraction has been developed and validated for the simultaneous quantification of paeoniflorinand albiflorin in rats plasma and tissue homogenate after administration of total glycosides of paeony （TGP）. Chromatographicseparation was achieved on a C15 column （150 mmx4.6 mm, 5 pro） with mobile phase consisted of acetonitrile-0.05% formicacid aqueous （20： 80, v/v） at a flow rate of 0.5 mL/min. The analytes were detected with triple-quadrupole mass spectrometer usingturbo ion spray with negative ionization in the multiple reaction-monitoring （MRM） modes. The results of method validationconformed to the requirements for the determination of biological samples. This method was successfully applied to thepharmacokinetics and tissue distribution study of TGP in rats. The results showed that paeonifiorin and albiflorin wereabsorbed and reached peak value quickly, and had the similar pharmacokinetic characteristics. Both of them underwent a rapid andwide distribution in the tissues throughout the whole body, among which stomach was the main distribution tissue. Moreover, theyhad the ability to cross the blood-brain barrier.
基金Supported by the National Natural Science Foundation of China(No.81673941,81603588 and 81804042)
文摘Objective: To summarize the evidence from systematic reviews(SRs) on the benefits and safety of Tripterygium glycosides(TG) and total glucosides of paeony(TGP), commonly used to treat rheumatoid arthritis(RA) in China, for patients with RA. Methods: SRs of randomized controlled trials(RCTs) on TG or TGP in treating RA were included, by searching 8 databases from their inception until December 2017. Two authors extracted data independently. We assessed the quality of SRs using AMSTAR and graded the quality of evidence according to the GRADE approach. Results: Eleven SRs containing an average of 7.6 RCTs, involving a total of 7,012 participants were included in this overview. On the basis of included SRs, TG and TGP could improve the following indexes for RA patients: American College of Rheumatology(ACR) 20 response rate, ACR50 response rate and ACR70 response rate, swollen joint count, tender joint count, erythrocyte sedimentation rate and C-reactive protein. Moreover, TGP could reduce incidence of hepatotoxicity. The most common adverse effects of TG were gastrointestinal discomfort and gonad toxicity, while for TGP was mild to moderate diarrhea. The overall quality of evidence for these findings ranged from "low" to "moderate". Conclusions: TG and TGP might be 2 potentially effective complementary and alternative drugs for patients with RA. Nevertheless, due to gonad toxicity, TG should only be considered in elderly patients or patients without reproductive needs. More evidence from high quality RCTs and SRs is warranted to support the use of TG and TGP for RA patients.
基金Innovation Team Project(Grant No.LT2015011)from the Education Department of Liaoning ProvinceImportant Sci entific and Technical Achievements Transformation Project(Gr ant No.Z17-5-078)+1 种基金Applied Basic Research Project(Grant No.F16205144)of Science and Technology Bureau of Shenyangthe Liaoning Provincial Education Department Project of China(Grant No.L2015192)
文摘Total paeony glycoside（TPG） is obtained from Radix Paeoniae Rubra with a variety of bioactivities. However, the low solubility and bioavailability limit its application. The present study aimed to develop TPG nanocrystals to increase the dissolution and then improve the oral bioavailability. TPG nanocrystals were prepared via precipitation and high-pressure homogenization method. The physical-chemical properties of the optimal TPG nanocrystals in terms of particle size, zeta potential, morphology and crystallinity were evaluated. The results showed that TPG nanocrystals had a mean particle size of（210.2±2.5） nm, a polydispersity index of 0.191±0.033 and a zeta potential of（–22.4±1.2） mV. The result of differential scanning calorimetry showed that the nanocrystals were still in crystalline state after the preparation procedure. Transmission electron microscopy（TEM） results showed that the nanosuspension was in spherical shape. The pharmacokinetics of TPG nanocrystals for rats was investigated by liquid chromatography-tandem mass spectroscopy（LC-MS/MS）. Compared with the TPG coarse suspension, TPG nanocrystals exhibited significant increase in AUC0–∞（approximately 1.85-fold）. Taken together, TPG nanocrystals could be used as a promising drug delivery system due to the enhanced oral bioavailability of TPG.
文摘目的:研究赤芍总苷对肺癌模型大鼠抑癌相关基因表达的影响。方法:将90只大鼠随机分为正常组、模型组、阳性对照组[环磷酰胺,50 mg/(kg·d)]和赤芍总苷低、中、高剂量组[50、100、200 mg/(kg·d)],每组15只。除正常组外,其余各组大鼠均采用左肺叶支气管内一次性灌注致癌碘油液复制肺癌模型,造模成功后,每周周一至周五各组大鼠于背iv相应药物,正常组和模型组iv等体积生理盐水,连续16周。采用逆转录-聚合酶链反应法测定大鼠肺组织中多药耐药相关蛋白(MRP)、人多药耐药基因(MDR1)和凋亡相关基因P21、P16 m RNA的表达;采用免疫组化法测定肺组织中抑癌基因P53蛋白的表达,计算其阳性率;观察肺组织病理变化。结果:与正常组比较,模型组大鼠肺组织中MRP、MDR1、P21、P16 m RNA及P53蛋白表达(阳性率为66.67%)水平明显升高(P<0.05);与模型组比较,阳性对照组和赤芍总苷低、中、高剂量组大鼠肺组织中MRP、MDR1、P21、P16 m RNA及P53蛋白表达(阳性率分别为46.67%、46.67%、40.00%、13.33%)水平降低并呈剂量依赖性,且赤芍总苷中、高剂量组比阳性对照组降低程度更显著(P<0.05);赤芍总苷各剂量组间比较,各指标差异均有统计学意义(P<0.05)。结论:赤芍总苷可明显抑制肺癌模型大鼠MRP、MDR1、P21、P16基因及P53蛋白的表达。
