类风湿性关节炎(RA)病势缠绵、较难治愈,常规治疗用药周期长、易诱发不良反应,特别需要考量患者的获益与风险。毒性中药川草乌作为RA治疗重要手段之一,用药存在一定争议。该研究切入临床用药的实际问题,基于多准则决策模型量化评估川...类风湿性关节炎(RA)病势缠绵、较难治愈,常规治疗用药周期长、易诱发不良反应,特别需要考量患者的获益与风险。毒性中药川草乌作为RA治疗重要手段之一,用药存在一定争议。该研究切入临床用药的实际问题,基于多准则决策模型量化评估川草乌中药单独应用以及联用西药的效益与风险。采用Rev Man 5.2软件分别综合21项川草乌单独应用治疗RA的随机对照试验(RCT)、49项川草乌联用西药治疗RA的RCT各指标结果,显示相较于常规西药治疗,无论单独应用还是联用西药,川草乌均可提高疗效、降低不良反应/事件发生率。结合RA治疗的效益-风险评价指标决策体系,应用Hiview 3软件以及Crystal Ball蒙特卡洛模拟计算川草乌单独应用与联用西药的效益值、风险值、效益-风险总值。结果显示川草乌联用西药的效益高于其单独应用(效益差=15,95%CI[9.72,20.25]),但其风险也相对更高(风险差=23,95%CI[15.57,30.55]),当效益与风险对RA患者同等重要时,川草乌单独应用的效益-风险总值为58,联用西药为55,且单独应用优于联用西药的概率为81.07%。由此可见,川草乌是RA临床治疗手段的重要补充,且当患者对于风险的可接受性较低时,则不推荐中西药联用。展开更多
Chuanwu(CW), a famous traditional Chinese medicine(TCM) from the mother roots of Aconitum carmichaelii Debx..(Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequen...Chuanwu(CW), a famous traditional Chinese medicine(TCM) from the mother roots of Aconitum carmichaelii Debx..(Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao(Radix Glyeyrrhizae, CG), Baishao(Radix Paeoniae Alba, CS) and Ganjiang(Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.展开更多
AIM: The aim of this work was to establish a specific and sensitive method to comprehensively investigate and compare chemical constituents of Fuzi-Gancao herb pair(FG), consisting of Aconitum carmichaelii Debeaux(Fuz...AIM: The aim of this work was to establish a specific and sensitive method to comprehensively investigate and compare chemical constituents of Fuzi-Gancao herb pair(FG), consisting of Aconitum carmichaelii Debeaux(Fuzi, Chinese) and Roast Radix Glycyrrhizae(Glycyrrhiza glabra L., Gancao, in Chinese) and Fuzi alone to explore the underlying interaction mechanism of FG. METHOD: An ultra-fast liquid chromatography-ion trap/time-of-flight mass spectrometry(UFLC/MS-IT-TOF) method using diazepam as internal standard was developed for the identification and semi-quantitative analysis of the phytochemical constituents of Fuzi and FG. Chromatographic separation was achieved on a UFLC column using a gradient program with 40 mmol?L-1 ammonium acetate and acetonitrile as the mobile phase. RESULTS: Fifty-one of the sixty compounds, including forty-five C19-diterpenoid alkaloids and six C20-diterpenoid alkaloids were tentatively identified in the extracts of Fuzi and FG through accurate mass measurements and fragmentation patterns. Comparing the contents of these alkaloids in these two extracts, it was found that the diester-diterpenoid alkaloids(DDAs) and the alkylolamine-diterpenoid alkaloids(ADAs) were increased, while the monoester-diterpenoid alkaloids(MDAs) were decreased in the extracts of FG. CONCLUSION: This work provided comprehensive information for the quality control of Fuzi preparations, and the further investigation on the compatibility mechanisms of FG.展开更多
Two new 2-(quinonylcarboxamino)benzoates, named aconicarmiquinamides A (1) and B (2), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii. Their structures were determined by spec...Two new 2-(quinonylcarboxamino)benzoates, named aconicarmiquinamides A (1) and B (2), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii. Their structures were determined by spectroscopic data analysis, and confirmed by comparison with synthetic methyl 3.6- bis( diethylamino )benzoqunonylcarboxylate (3).展开更多
文摘类风湿性关节炎(RA)病势缠绵、较难治愈,常规治疗用药周期长、易诱发不良反应,特别需要考量患者的获益与风险。毒性中药川草乌作为RA治疗重要手段之一,用药存在一定争议。该研究切入临床用药的实际问题,基于多准则决策模型量化评估川草乌中药单独应用以及联用西药的效益与风险。采用Rev Man 5.2软件分别综合21项川草乌单独应用治疗RA的随机对照试验(RCT)、49项川草乌联用西药治疗RA的RCT各指标结果,显示相较于常规西药治疗,无论单独应用还是联用西药,川草乌均可提高疗效、降低不良反应/事件发生率。结合RA治疗的效益-风险评价指标决策体系,应用Hiview 3软件以及Crystal Ball蒙特卡洛模拟计算川草乌单独应用与联用西药的效益值、风险值、效益-风险总值。结果显示川草乌联用西药的效益高于其单独应用(效益差=15,95%CI[9.72,20.25]),但其风险也相对更高(风险差=23,95%CI[15.57,30.55]),当效益与风险对RA患者同等重要时,川草乌单独应用的效益-风险总值为58,联用西药为55,且单独应用优于联用西药的概率为81.07%。由此可见,川草乌是RA临床治疗手段的重要补充,且当患者对于风险的可接受性较低时,则不推荐中西药联用。
基金supported by the Key Program of National Natural Science Foundation of China(Nos.81430093,81173500,81373930,81302905,81102556,and 81202639)National Key Subject of Drug Innovation(Nos.2015ZX09101043-005 and 2015ZX09101043-011)+1 种基金Heilongjiang University of Chinese Medicine Scientific Research Fund Projects(No.201307)Application Technology and Development of Youth Talents Project of Harbin,China(2014RFQXJ116)
文摘Chuanwu(CW), a famous traditional Chinese medicine(TCM) from the mother roots of Aconitum carmichaelii Debx..(Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao(Radix Glyeyrrhizae, CG), Baishao(Radix Paeoniae Alba, CS) and Ganjiang(Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20131310)the open project program of Key Laboratory of Drug Quality Control and Pharmacovigilance,Ministry of Education(No.MKLDP2013MS02)
文摘AIM: The aim of this work was to establish a specific and sensitive method to comprehensively investigate and compare chemical constituents of Fuzi-Gancao herb pair(FG), consisting of Aconitum carmichaelii Debeaux(Fuzi, Chinese) and Roast Radix Glycyrrhizae(Glycyrrhiza glabra L., Gancao, in Chinese) and Fuzi alone to explore the underlying interaction mechanism of FG. METHOD: An ultra-fast liquid chromatography-ion trap/time-of-flight mass spectrometry(UFLC/MS-IT-TOF) method using diazepam as internal standard was developed for the identification and semi-quantitative analysis of the phytochemical constituents of Fuzi and FG. Chromatographic separation was achieved on a UFLC column using a gradient program with 40 mmol?L-1 ammonium acetate and acetonitrile as the mobile phase. RESULTS: Fifty-one of the sixty compounds, including forty-five C19-diterpenoid alkaloids and six C20-diterpenoid alkaloids were tentatively identified in the extracts of Fuzi and FG through accurate mass measurements and fragmentation patterns. Comparing the contents of these alkaloids in these two extracts, it was found that the diester-diterpenoid alkaloids(DDAs) and the alkylolamine-diterpenoid alkaloids(ADAs) were increased, while the monoester-diterpenoid alkaloids(MDAs) were decreased in the extracts of FG. CONCLUSION: This work provided comprehensive information for the quality control of Fuzi preparations, and the further investigation on the compatibility mechanisms of FG.
基金Financial support from the National Natural Science Foundation of China (Nos.21132009 and 30825044)the Program for Changjiang Scholars and Innovative Research Team in University (No.IRT1007)the National Science and Technology Project of China (Nos.2012ZX09301002-002 and 2011ZX0 9307-002-01)
文摘Two new 2-(quinonylcarboxamino)benzoates, named aconicarmiquinamides A (1) and B (2), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii. Their structures were determined by spectroscopic data analysis, and confirmed by comparison with synthetic methyl 3.6- bis( diethylamino )benzoqunonylcarboxylate (3).