Objective:To investigate the plasma pharmacokinetics of six representative components(nodakenin,osthole,5-O-methylvisammioside,ferulic acid,liquiritigenin,and liquiritin),which were the ingredients of Qianghuo Shengsh...Objective:To investigate the plasma pharmacokinetics of six representative components(nodakenin,osthole,5-O-methylvisammioside,ferulic acid,liquiritigenin,and liquiritin),which were the ingredients of Qianghuo Shengshi Decoction(QSD)granules,in normal and rheumatoid arthritis(RA)rats administrated QSD granules intragastrically.Methods:A rapid and accurate ultra-high performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for the simultaneous determination of six components in plasma,and it showed a good specificity,linearity,intra-day and inter-day precision,intra-day and inter-day accuracy,extraction recovery,stability,and the less matrix effect.Results:The validated LC-MS/MS method was successfully used to compare the plasma pharmacokinetics of six ingredients between normal and RA rats after intragastrical administration of QSD granules and differences in the pharmacokinetics were found in two types of rats.The absorption rate in the RA rats was lower for nodakenin,osthole,5-O-methylvisammioside,liquiritigenin and liquiritin than in the normal group,while the absorption rate of ferulic acid remained constant in two groups.In comparison with the normal rats,the exposure concentration of nodakenin was higher and that of other five components except for nodakenin was lower under pathological conditions.Additionally,the absorptive amount of nodakenin,osthole,5-O-methylvisammioside and liquiritin was increased and that of ferulic acid and liquiritigenin was reduced in the RA rats than in the normal rats.Compared with the normal rats,the retention time of nodakenin,ferulic acid and liquiritin was reduced in vivo,whereas the retention time of osthole,5-O-methylvisammioside and liquiritigenin was raised in the body for the RA rats.In contrast to the normal rats,the data demonstrated an increase in the elimination velocity of nodakenin and a decrease in the elimination velocity of the other five components except for nodakenin in the pathological state.Conclusion:This study showed that the pharmacokinetic behavior of the six components,nodakenin,osthole,5-O-methylvisammioside,ferulic acid,liquiritigenin,and liquiritin,is different in vivo between normal and pathological states of rats,and this research provided the necessary experimental data to explain the pharmacokinetics of QSD granules in both normal and pathological states and provide some references for its clinical application at some level.展开更多
Objective： To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe （益肾祛风胜湿方, YQSR） in patients with glomerular proteinuria. Methods： A total of 145 patients with glomerular proteinuria were selec...Objective： To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe （益肾祛风胜湿方, YQSR） in patients with glomerular proteinuria. Methods： A total of 145 patients with glomerular proteinuria were selected and randomly assigned to the treatment group （108 cases） and the control group （37 cases） according to a random number table in a ratio of 3：1. All patients received conventional and symptomatic treatment. In addition, patients in the treatment and control groups were given YQSR （200 mL, twice per day, orally） and losartan （50 mg/d orally）, respectively for 6 months. The 24-h urine protein quantity, blood urea nitrogen, and serum creatinine in the two groups were measured at multiple time points before and after treatment. Results： At the end of the study, 5 cases were lost to follow-up in the treatment group and 1 in the control group. Finally, the statistical data included 103 cases in the treatment group and 36 cases in the control group. The total effectiveness after 2, 4, and 6 months was 81.6% （84/103）, 87.4% （90/103）, and 92.2% （95/103）, respectively, in the treatment group and 47.2% （17/36）, 55.6% （20/36）, and 61.1% （22/36）, respectively, in the control group, with significant difference between the two groups （P〈0.01 at all observation points）. In the treatment group, the curative effect after 6 months was better than that after 2 months （P〈0.05）. The 24-h urine protein quantity was significantly lower in the treatment group at 3, 4, 5, and 6 months than that in the control group （P〈0.05 or P〈0.01, respectively）. Conclusion： YQSR could significantly reduce the amount of glomerular proteinuria in the early stage.展开更多
目的:利用生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制。方法:通过美国国家生物技术信息中心数据库(national center for biotechnology information,NCBI)、高通量基因表达数据库(gene expression omnibus,GEO...目的:利用生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制。方法:通过美国国家生物技术信息中心数据库(national center for biotechnology information,NCBI)、高通量基因表达数据库(gene expression omnibus,GEO)等数据库检索强直性脊柱炎相关芯片,利用R语言分析得到差异表达基因。借助人类基因数据库(GeneCards)、疾病基因数据库(DisGeNET)、孟德尔遗传综合数据库(online Mendelian inheritance in man,OMIM)、疾病数据库(MalaCards)、遗传药理学和药物基因组学数据库(pharmacogenetics and pharmacogenomics knowledge base,PharmGKB)等数据库对强直性脊柱炎已知靶基因进行检索与筛选,与差异表达基因去重取并集,对强直性脊柱炎的疾病靶基因进行预测。运用中药药理学平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)数据库对羌活胜湿汤七味中药的主要有效成分及作用靶基因进行筛选和挖掘,构建药物与疾病映射靶基因的蛋白质互作(protein-protein interaction,PPI)网络,通过基因注释(database for annotation,visualization and integrated discovery,David)数据库对药物-疾病关键靶基因进行生物通路及富集分析。最终将羌活胜湿汤中主要有效成分与关键靶基因进行分子对接。结果:羌活胜湿汤有效成分-靶基因网络图包含176个有效成分,相对应靶点137个;GEO数据库获得差异表达基因704个,通过疾病数据库检索与强直性脊柱炎发生发展相关的已知疾病靶标1323个,合并去重后共获得1950个已知疾病靶基因;最终获得映射靶基因46个,关键靶基因13个。羌活胜湿汤主要通过肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素1β(interleukin-1β,IL-1β)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、氯霉素乙酰转移酶基因(chloramphnicol acetyltransferase,CAT)、雌激素受体1(estrogen receptor 1,ESR1)、环加氧酶2(prostaglandin-endoperoxide synthase 2,PTGS2)等作用于脂多糖介导的信号通路、一氧化氮生物合成过程的正调控、血管生成等生物过程及FoxO信号通路、炎症性肠病、各促炎因子相关信号通路等多个信号通路。分子对接结果显示:羌活胜湿汤中主要有效成分在与关键靶基因对接过程中均进入了活性位点,具有很强的结合能力。结论:应用生物信息学和分子对接技术方法可揭示羌活胜湿汤治疗强直性脊柱炎的潜在作用机制,具有较高的置信度和参考价值,为中药组方在治疗强直性脊柱炎方面提供了新的方向与思路。展开更多
基金supported by the Science and Technology Program of Tianjin(No.21ZYJDJC00020)“Youth Qi Huang Scholar”by State Administration of TCM,and the Science and Technology Program of Haihe Laboratory of Modern Chinese Medicine(No.22HHZYSS00005).
文摘Objective:To investigate the plasma pharmacokinetics of six representative components(nodakenin,osthole,5-O-methylvisammioside,ferulic acid,liquiritigenin,and liquiritin),which were the ingredients of Qianghuo Shengshi Decoction(QSD)granules,in normal and rheumatoid arthritis(RA)rats administrated QSD granules intragastrically.Methods:A rapid and accurate ultra-high performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for the simultaneous determination of six components in plasma,and it showed a good specificity,linearity,intra-day and inter-day precision,intra-day and inter-day accuracy,extraction recovery,stability,and the less matrix effect.Results:The validated LC-MS/MS method was successfully used to compare the plasma pharmacokinetics of six ingredients between normal and RA rats after intragastrical administration of QSD granules and differences in the pharmacokinetics were found in two types of rats.The absorption rate in the RA rats was lower for nodakenin,osthole,5-O-methylvisammioside,liquiritigenin and liquiritin than in the normal group,while the absorption rate of ferulic acid remained constant in two groups.In comparison with the normal rats,the exposure concentration of nodakenin was higher and that of other five components except for nodakenin was lower under pathological conditions.Additionally,the absorptive amount of nodakenin,osthole,5-O-methylvisammioside and liquiritin was increased and that of ferulic acid and liquiritigenin was reduced in the RA rats than in the normal rats.Compared with the normal rats,the retention time of nodakenin,ferulic acid and liquiritin was reduced in vivo,whereas the retention time of osthole,5-O-methylvisammioside and liquiritigenin was raised in the body for the RA rats.In contrast to the normal rats,the data demonstrated an increase in the elimination velocity of nodakenin and a decrease in the elimination velocity of the other five components except for nodakenin in the pathological state.Conclusion:This study showed that the pharmacokinetic behavior of the six components,nodakenin,osthole,5-O-methylvisammioside,ferulic acid,liquiritigenin,and liquiritin,is different in vivo between normal and pathological states of rats,and this research provided the necessary experimental data to explain the pharmacokinetics of QSD granules in both normal and pathological states and provide some references for its clinical application at some level.
文摘Objective： To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe （益肾祛风胜湿方, YQSR） in patients with glomerular proteinuria. Methods： A total of 145 patients with glomerular proteinuria were selected and randomly assigned to the treatment group （108 cases） and the control group （37 cases） according to a random number table in a ratio of 3：1. All patients received conventional and symptomatic treatment. In addition, patients in the treatment and control groups were given YQSR （200 mL, twice per day, orally） and losartan （50 mg/d orally）, respectively for 6 months. The 24-h urine protein quantity, blood urea nitrogen, and serum creatinine in the two groups were measured at multiple time points before and after treatment. Results： At the end of the study, 5 cases were lost to follow-up in the treatment group and 1 in the control group. Finally, the statistical data included 103 cases in the treatment group and 36 cases in the control group. The total effectiveness after 2, 4, and 6 months was 81.6% （84/103）, 87.4% （90/103）, and 92.2% （95/103）, respectively, in the treatment group and 47.2% （17/36）, 55.6% （20/36）, and 61.1% （22/36）, respectively, in the control group, with significant difference between the two groups （P〈0.01 at all observation points）. In the treatment group, the curative effect after 6 months was better than that after 2 months （P〈0.05）. The 24-h urine protein quantity was significantly lower in the treatment group at 3, 4, 5, and 6 months than that in the control group （P〈0.05 or P〈0.01, respectively）. Conclusion： YQSR could significantly reduce the amount of glomerular proteinuria in the early stage.
文摘目的:利用生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制。方法:通过美国国家生物技术信息中心数据库(national center for biotechnology information,NCBI)、高通量基因表达数据库(gene expression omnibus,GEO)等数据库检索强直性脊柱炎相关芯片,利用R语言分析得到差异表达基因。借助人类基因数据库(GeneCards)、疾病基因数据库(DisGeNET)、孟德尔遗传综合数据库(online Mendelian inheritance in man,OMIM)、疾病数据库(MalaCards)、遗传药理学和药物基因组学数据库(pharmacogenetics and pharmacogenomics knowledge base,PharmGKB)等数据库对强直性脊柱炎已知靶基因进行检索与筛选,与差异表达基因去重取并集,对强直性脊柱炎的疾病靶基因进行预测。运用中药药理学平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)数据库对羌活胜湿汤七味中药的主要有效成分及作用靶基因进行筛选和挖掘,构建药物与疾病映射靶基因的蛋白质互作(protein-protein interaction,PPI)网络,通过基因注释(database for annotation,visualization and integrated discovery,David)数据库对药物-疾病关键靶基因进行生物通路及富集分析。最终将羌活胜湿汤中主要有效成分与关键靶基因进行分子对接。结果:羌活胜湿汤有效成分-靶基因网络图包含176个有效成分,相对应靶点137个;GEO数据库获得差异表达基因704个,通过疾病数据库检索与强直性脊柱炎发生发展相关的已知疾病靶标1323个,合并去重后共获得1950个已知疾病靶基因;最终获得映射靶基因46个,关键靶基因13个。羌活胜湿汤主要通过肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素1β(interleukin-1β,IL-1β)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、氯霉素乙酰转移酶基因(chloramphnicol acetyltransferase,CAT)、雌激素受体1(estrogen receptor 1,ESR1)、环加氧酶2(prostaglandin-endoperoxide synthase 2,PTGS2)等作用于脂多糖介导的信号通路、一氧化氮生物合成过程的正调控、血管生成等生物过程及FoxO信号通路、炎症性肠病、各促炎因子相关信号通路等多个信号通路。分子对接结果显示:羌活胜湿汤中主要有效成分在与关键靶基因对接过程中均进入了活性位点,具有很强的结合能力。结论:应用生物信息学和分子对接技术方法可揭示羌活胜湿汤治疗强直性脊柱炎的潜在作用机制,具有较高的置信度和参考价值,为中药组方在治疗强直性脊柱炎方面提供了新的方向与思路。
