Objective:To predict and analyze the potential Q-markers of Chuanxiong Chatiao Prescription,and the pharmacokinetic properties of pulvis and pills in vivo were studied,which provided a basis for the rational evaluatio...Objective:To predict and analyze the potential Q-markers of Chuanxiong Chatiao Prescription,and the pharmacokinetic properties of pulvis and pills in vivo were studied,which provided a basis for the rational evaluation of the phenomenon of“Different Dosage Forms of the Same Prescription”.Methods and Material:Q-markers analysis of Chuanxiong Chatiao Prescription based on the“Five Principles”(traceability and transmissibility,specificity,effectiveness,prescription compatibility and testability).The content determination method of Q-markers in Chuanxiong Chatiao Prescription was established by UPLC,and the content difference of Q-markers in the two dosage forms ware determined and compared.The Q-markers in rabbit plasma was determined by LC-MS/MS method,and the pharmacokinetic parameters of Q-markers in pulvis and pills were analyzed.Results:A total of 16 potential Q-markers from the“Five Principles”were used,nine components of tetramethylprazine,ferulic acid,glycyrrhizin,glycyrrhizic acid,luteolin,cimicifugoside,senkyunolideⅠ,isoimperatorin,nodakenin were identified as Q-markers of Chuanxiong Chatiao Presciption.The content of tetramethylprazine and other components in the pulvis form was found to be significantly higher than that in the pills,while the content of senkyunolideⅠwas lower than that in the pills,which may be related to the preparation process of the dosage form and the physicochemical properties of the components.Compared with pulvis,the Tmax and t_(1/2)of ferulic acid and other components in pills were significantly prolonged.To a certain extent,it can explain the classical theory of traditional Chinese medicine“Components in pulvis release quickly and take effect in fast-acting manner,while in pills release slowly and take effect in slow-acting”.Meanwhile,the Cmax and AUC0-t of tetramethylprazine and other components in pills were higher than those in pulvis,which showed unexpected pharmacokinetic characteristics,indicating the complexity of compounding and the importance of dosage form design.Conclusions:A method for the determination of Q-markers content was established by UPLC,which provide reference for the quality control of Chuanxiong Chatiao Prescription.In vivo studies have found the pharmacokinetic parameters indicate the absorption and distribution characteristics of pulvis and pills.However,it is also found that the release behavior of different components not only affected by the dosage form but also closely related to their own physical and chemical properties.展开更多
Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風...Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) and its composed crude drug, gardeniae fructus (GF: 山梔子) were investigated on levels of these diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in STZ-diabetic mice. BOF and GF were extracted in 10 volumes of distilled water with an automatic extractor “Torobi”. STZ-induced diabetic mice with serum glucose level of over 600 mg/dl at 3 - 4 weeks after intravenous injection of 150 mg/kg STZ were used for experiments. BOF extract, GF extract, geniposide (a main constituent of GF), and glibenclamide were administered intraperitoneally into 3-hour-fasted STZ-diabetic mice. At 6 hours after administration, BOF extract (100 - 300 mg/kg) decreased high levels of serum glucose, triglyceride and cholesterol, and also increased low level of serum insulin in STZ-diabetic mice in a dose-dependent manner, respectively. Anti-diabetic drug glibenclamide (0.3 - 1 mg/kg) as positive control significantly decreased serum glucose and cholesterol levels, and increased serum insulin level in the diabetic mice. GF extract (30 - 300 mg/kg) decreased serum glucose, triglyceride and cholesterol levels but did not affect serum insulin level in the diabetic mice. Geniposide (10 - 100 mg/kg), decreased serum glucose level but did not affect serum insulin and triglyceride levels in the diabetic mice. These results demonstrated that intraperitoneally administrated BOF extract improved abnormal levels of serum glucose, insulin, triglyceride and cholesterol in the STZ-diabetic mice as being similar to glibenclamide. GF extract has an important role in a part of improving actions of BOF in the diabetic mice. The action of GF extract on serum glucose was parallel with the action of geniposide in the diabetic mice, supporting roles of geniposide in anti-hyperglycemic action of GF.展开更多
基金supported by Chinese Medicine Pharmaceutical Key Discipline of Shaanxi province(No.303061107)National key Research and Development plan(No.2018-YFC1706904)+1 种基金Discipline Innovation team Project of Shaanxi University of Chinese Medicine(No.2019-YL11)Shaanxi Province Key subject of pharmacy engineering of Shaanxi Provincial Traditional Chinese Medicine administration(No.2017001).
文摘Objective:To predict and analyze the potential Q-markers of Chuanxiong Chatiao Prescription,and the pharmacokinetic properties of pulvis and pills in vivo were studied,which provided a basis for the rational evaluation of the phenomenon of“Different Dosage Forms of the Same Prescription”.Methods and Material:Q-markers analysis of Chuanxiong Chatiao Prescription based on the“Five Principles”(traceability and transmissibility,specificity,effectiveness,prescription compatibility and testability).The content determination method of Q-markers in Chuanxiong Chatiao Prescription was established by UPLC,and the content difference of Q-markers in the two dosage forms ware determined and compared.The Q-markers in rabbit plasma was determined by LC-MS/MS method,and the pharmacokinetic parameters of Q-markers in pulvis and pills were analyzed.Results:A total of 16 potential Q-markers from the“Five Principles”were used,nine components of tetramethylprazine,ferulic acid,glycyrrhizin,glycyrrhizic acid,luteolin,cimicifugoside,senkyunolideⅠ,isoimperatorin,nodakenin were identified as Q-markers of Chuanxiong Chatiao Presciption.The content of tetramethylprazine and other components in the pulvis form was found to be significantly higher than that in the pills,while the content of senkyunolideⅠwas lower than that in the pills,which may be related to the preparation process of the dosage form and the physicochemical properties of the components.Compared with pulvis,the Tmax and t_(1/2)of ferulic acid and other components in pills were significantly prolonged.To a certain extent,it can explain the classical theory of traditional Chinese medicine“Components in pulvis release quickly and take effect in fast-acting manner,while in pills release slowly and take effect in slow-acting”.Meanwhile,the Cmax and AUC0-t of tetramethylprazine and other components in pills were higher than those in pulvis,which showed unexpected pharmacokinetic characteristics,indicating the complexity of compounding and the importance of dosage form design.Conclusions:A method for the determination of Q-markers content was established by UPLC,which provide reference for the quality control of Chuanxiong Chatiao Prescription.In vivo studies have found the pharmacokinetic parameters indicate the absorption and distribution characteristics of pulvis and pills.However,it is also found that the release behavior of different components not only affected by the dosage form but also closely related to their own physical and chemical properties.
文摘Streptozotocin (STZ)-induced diabetic mice increased levels of serum glucose, triglyceride and cholesterol, and decreased level of serum insulin. Effects of Bofutsushosan (BOF: Pulvis ledebouriellae compositae: 防風通聖散) and its composed crude drug, gardeniae fructus (GF: 山梔子) were investigated on levels of these diabetic parameters (serum glucose, insulin, triglyceride and cholesterol) in STZ-diabetic mice. BOF and GF were extracted in 10 volumes of distilled water with an automatic extractor “Torobi”. STZ-induced diabetic mice with serum glucose level of over 600 mg/dl at 3 - 4 weeks after intravenous injection of 150 mg/kg STZ were used for experiments. BOF extract, GF extract, geniposide (a main constituent of GF), and glibenclamide were administered intraperitoneally into 3-hour-fasted STZ-diabetic mice. At 6 hours after administration, BOF extract (100 - 300 mg/kg) decreased high levels of serum glucose, triglyceride and cholesterol, and also increased low level of serum insulin in STZ-diabetic mice in a dose-dependent manner, respectively. Anti-diabetic drug glibenclamide (0.3 - 1 mg/kg) as positive control significantly decreased serum glucose and cholesterol levels, and increased serum insulin level in the diabetic mice. GF extract (30 - 300 mg/kg) decreased serum glucose, triglyceride and cholesterol levels but did not affect serum insulin level in the diabetic mice. Geniposide (10 - 100 mg/kg), decreased serum glucose level but did not affect serum insulin and triglyceride levels in the diabetic mice. These results demonstrated that intraperitoneally administrated BOF extract improved abnormal levels of serum glucose, insulin, triglyceride and cholesterol in the STZ-diabetic mice as being similar to glibenclamide. GF extract has an important role in a part of improving actions of BOF in the diabetic mice. The action of GF extract on serum glucose was parallel with the action of geniposide in the diabetic mice, supporting roles of geniposide in anti-hyperglycemic action of GF.
