目的研究大黄标准汤剂的量值传递规律。方法制备23批大黄标准汤剂,建立标准汤剂及其原料饮片的HPLC指纹图谱,标定共有峰,采用四级杆飞行时间高分辨质谱(quadrupole time-of-flight mass spectrometry,Q-TOF-MS/MS)对共有峰进行鉴定,分...目的研究大黄标准汤剂的量值传递规律。方法制备23批大黄标准汤剂,建立标准汤剂及其原料饮片的HPLC指纹图谱,标定共有峰,采用四级杆飞行时间高分辨质谱(quadrupole time-of-flight mass spectrometry,Q-TOF-MS/MS)对共有峰进行鉴定,分别测定饮片和标准汤剂中8个结合型蒽醌(芦荟大黄素-8-O-葡萄糖苷、大黄酸-8-O-葡萄糖苷、大黄素-1-O-葡萄糖苷、大黄酚-1-O-葡萄糖苷、大黄酚-8-O-葡萄糖苷、芦荟大黄素-3-羟甲基-O-葡萄糖苷、大黄素-8-O-葡萄糖苷、大黄素甲醚-8-O-葡萄糖苷)、5个游离型蒽醌(芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚)、4个鞣质类成分(没食子酸、儿茶素、表儿茶素、表儿茶素没食子酸酯)和1个二苯乙烯类成分[白藜芦醇4′-O-β-D-(6″-O-没食子酰)-葡萄糖苷(RGG)]的含量及标准汤剂出膏率,以共有峰传递数、成分转移率及出膏率为指标,分析大黄标准汤剂的量值传递规律。结果大黄饮片指纹图谱标定共有峰45个,其中40个传递到了标准汤剂,40个共有峰的成分均得到鉴定,其中8个结合型蒽醌、5个游离型蒽醌、2个蒽酮类成分、5个鞣质类成分、2个二苯乙烯类成分采用对照品比对确认。8个结合型蒽醌和5个游离型蒽醌合计的平均转移率分别为43.83%和11.03%,没食子酸、儿茶素、表儿茶素和表儿茶素没食子酸酯的平均转移率分别为233.00%、79.58%、303.18%和58.71%,RGG的平均转移率为68.89%,标准汤剂平均出膏率为23.26%。结论研究结果为大黄配方颗粒和含大黄经典名方制剂工艺研究和质量评价奠定了基础。展开更多
Anthrones are key structural motifs in many natural products, bioactive compounds and pharmaceutical chemicals. Earth-abundant-metal-catalyzed asymmetric functionalization of anthrones has not proved to be viable. Her...Anthrones are key structural motifs in many natural products, bioactive compounds and pharmaceutical chemicals. Earth-abundant-metal-catalyzed asymmetric functionalization of anthrones has not proved to be viable. Herein, we disclosed a highly enantioselective propargylic substitution of anthrones with propargylic esters using copper salts with chiral N, N, P-ligand. This strategy is amenable to a broad range of substrates, uses readily available starting materials, provides excellent yields with remarkable enantioselectivity under mild conditions, and enables attractive products diversification routes.展开更多
Objective:To determine the mechanism of the laxative effect of rhubarb(Rheum tanguticum Maxim.ex Balf.)in rats using a combined bioinformatic and in vivo approach.Methods:Substances derived from rhubarb that are prese...Objective:To determine the mechanism of the laxative effect of rhubarb(Rheum tanguticum Maxim.ex Balf.)in rats using a combined bioinformatic and in vivo approach.Methods:Substances derived from rhubarb that are present in the colorectum were identified using high-performance liquid chromatography,coupled with linear ion-trap quadrupole Orbitrap highresolution mass spectrometry.The targets with a potential laxative effect were identified from databases and the literature,then used with rhubarb-derived substances in molecular docking modeling.The expression of candidate endogenous target molecules that bound specific components of rhubarb was then measured in constipated rats that had or had not been administered rhubarb by western blotting.Finally,potentially bioactive compounds were traced back to their prototype components.Results:We identified 17 anthraquinones and 21 anthrones derived from rhubarb in the colorectum of rats.G-scoring identified three potential mediators of the laxative effect:c-kit,5-hydroxytryptamine receptor 4(5-HT4),and aquaporin-3(AQP3).In addition,10 rhubarb-derived components(aloeemodin,emodin,rhein,chrysophanol,physcion,sennoside A,sennoside C,physcionanthrone,aloeemodinanthrone,and rheinanthrone),which have strong binding affinities for more than one of the three potential targets,were selected as likely active compounds.Rhubarb extract increased the expression of c-kit and 5-HT4,and reduced the expression of AQP3 in the colon of constipated rats,which might mediate its laxative effect.We also found that a single prototype component may be metabolized into several active metabolites,and a single active ingredient can also be generated from various prototype compounds.Conclusion:The present study demonstrates that various anthraquinones and anthrones present in rhubarb may be metabolized to form bioactive compounds that have additive or synergistic effects to promote defecation via c-kit,5-HT4 and/or AQP3.展开更多
文摘目的研究大黄标准汤剂的量值传递规律。方法制备23批大黄标准汤剂,建立标准汤剂及其原料饮片的HPLC指纹图谱,标定共有峰,采用四级杆飞行时间高分辨质谱(quadrupole time-of-flight mass spectrometry,Q-TOF-MS/MS)对共有峰进行鉴定,分别测定饮片和标准汤剂中8个结合型蒽醌(芦荟大黄素-8-O-葡萄糖苷、大黄酸-8-O-葡萄糖苷、大黄素-1-O-葡萄糖苷、大黄酚-1-O-葡萄糖苷、大黄酚-8-O-葡萄糖苷、芦荟大黄素-3-羟甲基-O-葡萄糖苷、大黄素-8-O-葡萄糖苷、大黄素甲醚-8-O-葡萄糖苷)、5个游离型蒽醌(芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚)、4个鞣质类成分(没食子酸、儿茶素、表儿茶素、表儿茶素没食子酸酯)和1个二苯乙烯类成分[白藜芦醇4′-O-β-D-(6″-O-没食子酰)-葡萄糖苷(RGG)]的含量及标准汤剂出膏率,以共有峰传递数、成分转移率及出膏率为指标,分析大黄标准汤剂的量值传递规律。结果大黄饮片指纹图谱标定共有峰45个,其中40个传递到了标准汤剂,40个共有峰的成分均得到鉴定,其中8个结合型蒽醌、5个游离型蒽醌、2个蒽酮类成分、5个鞣质类成分、2个二苯乙烯类成分采用对照品比对确认。8个结合型蒽醌和5个游离型蒽醌合计的平均转移率分别为43.83%和11.03%,没食子酸、儿茶素、表儿茶素和表儿茶素没食子酸酯的平均转移率分别为233.00%、79.58%、303.18%和58.71%,RGG的平均转移率为68.89%,标准汤剂平均出膏率为23.26%。结论研究结果为大黄配方颗粒和含大黄经典名方制剂工艺研究和质量评价奠定了基础。
基金financial support from the National Natural Science Foundation of China (No.21801087)Fundamental Research Funds for the Central Universities CCNU (No.CCNU19QN064)+2 种基金the Ministry of Science and Technology of China (No.2016YFE0132600)Henan Center for Outstanding Overseas Scientists (No.GZS2020001)the Key Scientific and Technological Project of Henan Province (No.212102311068)。
文摘Anthrones are key structural motifs in many natural products, bioactive compounds and pharmaceutical chemicals. Earth-abundant-metal-catalyzed asymmetric functionalization of anthrones has not proved to be viable. Herein, we disclosed a highly enantioselective propargylic substitution of anthrones with propargylic esters using copper salts with chiral N, N, P-ligand. This strategy is amenable to a broad range of substrates, uses readily available starting materials, provides excellent yields with remarkable enantioselectivity under mild conditions, and enables attractive products diversification routes.
基金the National Natural Science Foundation of China(81673562 and 81973467)the Fundamental Research Funds for the Central Universities of China(2020-JYB-ZDGG-033).
文摘Objective:To determine the mechanism of the laxative effect of rhubarb(Rheum tanguticum Maxim.ex Balf.)in rats using a combined bioinformatic and in vivo approach.Methods:Substances derived from rhubarb that are present in the colorectum were identified using high-performance liquid chromatography,coupled with linear ion-trap quadrupole Orbitrap highresolution mass spectrometry.The targets with a potential laxative effect were identified from databases and the literature,then used with rhubarb-derived substances in molecular docking modeling.The expression of candidate endogenous target molecules that bound specific components of rhubarb was then measured in constipated rats that had or had not been administered rhubarb by western blotting.Finally,potentially bioactive compounds were traced back to their prototype components.Results:We identified 17 anthraquinones and 21 anthrones derived from rhubarb in the colorectum of rats.G-scoring identified three potential mediators of the laxative effect:c-kit,5-hydroxytryptamine receptor 4(5-HT4),and aquaporin-3(AQP3).In addition,10 rhubarb-derived components(aloeemodin,emodin,rhein,chrysophanol,physcion,sennoside A,sennoside C,physcionanthrone,aloeemodinanthrone,and rheinanthrone),which have strong binding affinities for more than one of the three potential targets,were selected as likely active compounds.Rhubarb extract increased the expression of c-kit and 5-HT4,and reduced the expression of AQP3 in the colon of constipated rats,which might mediate its laxative effect.We also found that a single prototype component may be metabolized into several active metabolites,and a single active ingredient can also be generated from various prototype compounds.Conclusion:The present study demonstrates that various anthraquinones and anthrones present in rhubarb may be metabolized to form bioactive compounds that have additive or synergistic effects to promote defecation via c-kit,5-HT4 and/or AQP3.
