Moutan Cortex (MC) has been demonstrated to have an inhibitive effect on inflammation and oxidative stress responses in mesangial cells in our previous study. However, little is known about the components of MC contri...Moutan Cortex (MC) has been demonstrated to have an inhibitive effect on inflammation and oxidative stress responses in mesangial cells in our previous study. However, little is known about the components of MC contributing to this benefit. In the present study, cell membrane immobilized chromatography (CMC), a fast and useful method, was presented for screening potential active components of MC. HBZY-1 cells were incubated with MC (200 μg/mL) at the optimal incubation time (90 min). HPLC-DAD analysis and LC/ESI/MS/MS were performed to distinguish the active components and identify its structural ion fragments. The results showed that eight components binding to HBZY-1 cells were mudanoside B, paeoniflorin sulfonate, paeoniflorin, tetragalloyl glucose (isomeride), hexagalloyl glucose, mudanopiside A, and paeonol. In conclusion, our established CMC might be a useful method for screening potential active components in complicated traditional Chinese medicines. These components might be associated with the efficacy of MC on prevention and treatment of diabetic nephropathy.展开更多
The present study was designed to investigate the therapeutic effcts of Moutan Cortex(CM,root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra(PR,root of Paeonia veitchii Lynch) on metabolic disorders,focus...The present study was designed to investigate the therapeutic effcts of Moutan Cortex(CM,root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra(PR,root of Paeonia veitchii Lynch) on metabolic disorders,focusing on the infuence of CM and PR on the obesity-related gut microbiota homeostasis.The diet-induced obese(DIO) mouse model was used to test the therapeutic effects of CM and PR.The mice were orally administered with CM and PR for 6 weeks,and oral glucose tolerance test(OGTT) and insulin tolerance test(ITT) were performed to evaluate the insulin sensitivity of the mice.Sterol-regulatory element binding proteins(SREBPs) and their target genes were measured by quantitative RT-PCR.High-throughput 16 S ribosomal RNA(16S rR NA) gene sequencing technology was used to determine the composition of gut microbiota,and the metabolites in serum were analyzed by GC-MS.Our results indicated that CM and PR combination alleviated obese and insulin resistance in the DIO mice,leading to increased glucose uptake and gene expression in muscle and liver,and down-regulated SREBPs and their target genes in liver.Interesting,neither the CM-PR extracts,nor the major components of CM and PR did not affect SREBPs activity in cultured cells.Meanwhile,CM and PR significantly modulated the gut microbiota of the high-fat diet(HFD) treated mice,similar to metformin,and CM-PR reversed the overall microbiota composition similar to the normal chow diet(NCD) treated mice.In conclusion,our results provide novel mechanisms of action for the effects of CM and PR in treating DIO-induced dysregulation of sugar and lipid metabolism.展开更多
Objective: Establish a quick, precise and specific method to determine whether the moutan cortex obtained from market is processed with sulfur; provide a reliable method for the scientific evaluation.Methods: Three me...Objective: Establish a quick, precise and specific method to determine whether the moutan cortex obtained from market is processed with sulfur; provide a reliable method for the scientific evaluation.Methods: Three methods, including acid-base titration method, high-performance liquid-chromatography(HPLC) method, and ultraperformance liquid chromatography coupled with time-of-flight mass spectrometry(UHPLC-TOF-MS) method were used to detect whether30 batches of samples were fumigated with sulfur.Results: The results of three methods were substantially the same. Fifteen batches were identified to have been processed with sulfur fumigation, while others were not.Conclusions: The HPLC method was found to be most appropriate for the determination of sulfur fumigation for moutan cortex.展开更多
Objective To identify the quality markers of Moutan Cortex(MC) and establish the quality evaluation methods for multi-component assay and fingerprinting of MC. Methods The chemical constituents in MC were identified b...Objective To identify the quality markers of Moutan Cortex(MC) and establish the quality evaluation methods for multi-component assay and fingerprinting of MC. Methods The chemical constituents in MC were identified by HPLC-QTOF-MS. UPLC was employed for the multi-component assay and fingerprinting of MC. Furthermore, text mining was carried out to review the biosynthesis pathways and pharmacological and pharmacokinetic studies related to MC, and in silico target fishing was conducted to construct compound-target networks for MC. Results Sixteen compounds were clearly identified in MC and their structures were confirmed through comparison with literature data. In addition, the biosynthetic pathways and component specificities of the identified compounds were summarized and confirmed by text mining.Pharmacological activities, including traditional usage and modern pharmacological studies were summarized. A total of 282 targets from Homo sapiens were fished for 13 compounds. In addition, pharmacokinetic studies of different compounds were synopsized. Finally, multi-component assay and fingerprint of MC were established. Conclusion Eight major components are selected as quality markers of MC, such as oxypaeoniflorin, apiopaeonoside, albiflorin, paeonolide, paeoniflorin, 1,2,3,4,6-penta-O-galloyl-β-D-glucose, mudanpioside C and paeonol. These eight quality markers are successfully applied to the quality evaluation of MC, and could be useful in improving the current quality standards of MC.展开更多
Cortex Moutan (Paeonia suffruticosa Andr.) is a common traditional Chinese medicine and has been widely used in clinic for 2000 years in China. As sources for this crude drug are always mixed with other species, many ...Cortex Moutan (Paeonia suffruticosa Andr.) is a common traditional Chinese medicine and has been widely used in clinic for 2000 years in China. As sources for this crude drug are always mixed with other species, many cultivars on herbal market may lead to quality instability. Multi-component quantitative analysis is an efficient method to reflect chemical profiles of herb medicine and is always taken as the main method for quality evaluation. So, the aim of this work is to develop analytical method to quantify paeonol, paeoniflorin, gallic acid, oxypaeoniflorin, benzoylpaeoniflorin and paeonolide in Cortex Moutan (CM) to evaluate the chemical qualities of CM from different species or cultivars. Besides, we also study the intestinal absorption characteristics of paeonol and paeoniflorin for further pharmacological evaluation. In the present study, all of the standard markers were performed on an Ecosil C18 (250 mm × 4.6 mm, 5 μM, Lubex Co., Guangzhou, China) with linear gradient elution of 0.2% formic acid water and acetonitrile. The proposed method was applied to analyze 50 batches of samples with acceptable linearity (R2, 0.9995 - 0.9999), precisions (RSD, 0.47% - 2.08%), repeatability (RSD, 039% - 2.63%), stability (RSD, 0.52% - 2.45%), and recovery (RSD, 0.72% - 3.03%) of the six compounds. Furthermore, the Hierarchical Cluster Analysis was applied to classify the 50 samples based on contents of the six compound markers. The results obtained from multi-component quantification of CM clearly indicated that CM originated from P. suffruticosa and P. ostii presented different chemical properties, and that samples from the two materials could be gathered into one branch, respectively, while CM sourced from cultivars of P. suffruticosa showed great variety on chemical quality. The results from Hierarchical Cluster Analysis implied that the established method could be used as a powerful tool for the quality evaluation of CM. The intestinal absorption study indicated that the intestinal absorption activities for paeoniflorin and paeonol showed an increasing absorption with time. Paeonol had lower absorption rate (6.69% - 15.93%) than that of paeoniflorin (19.0% - 30.70%). As a result, the established method is suitable for the quality evaluation of CM. The results of intestinal absorption characteristics of paeonol and paeoniflorin offer an insight for pharmacological evaluation and clinical efficacy research of CM.展开更多
Objective:To clarify the material basis of Chinese medicine pair“Radix Paeoniae Rubra-Cortex Moutan”(Chishao-Mudanpi)and explore their mechanism in the treatment of ICH with network pharmacology.Methods:The active i...Objective:To clarify the material basis of Chinese medicine pair“Radix Paeoniae Rubra-Cortex Moutan”(Chishao-Mudanpi)and explore their mechanism in the treatment of ICH with network pharmacology.Methods:The active ingredients contained in Radix Paeoniae Rubra and Cortex Moutan were searched and selected based on the oral bioavailability prediction and drug-likeness prediction from the TCMSP database.Then the targets of cerebral hemorrhage were collected from GeneCards,OMIM,and DrugBank databases.After obtained the intersections of drugs and disease,the active component target disease interactive network diagram was drawn by Cytoscape software.The obtained key targets were uploaded to the STRING database for analysis and construct a PPI network map.GO function enrichment analysis and KEGG analysis were performed on the key target proteins.Results:Collected the active ingredients of Radix Paeoniae 119,Radix Paeoniae 55,including paeoniflorin,baicalin,β-sitosterol,etc.Related drug target protein 1190,ICH disease-related genes 823,"Radix Paeoniae-Radix Paeoniae"and 72 common targets of ICH,mainly acting on Akt1,IL6,VEGFA,CASP3,EGF,involving 133 related signaling pathways such as AGE-RAGE,TNF,IL-17,HIF1,PI3K-Akt.Conclusion:The combination of"Radix Paeoniae Rubra-Cortex Moutan"in the treatment of ICH has the characteristics of multiple pathways and multiple targets,which provides a reference and basis for further molecular biology verification in the future.展开更多
Metastases are the main cause of death among patients with bladder cancer, which is the second most common malignancy of the genitourinary tract and is highly prevalent in the southwestern region of Taiwan. Angiogenes...Metastases are the main cause of death among patients with bladder cancer, which is the second most common malignancy of the genitourinary tract and is highly prevalent in the southwestern region of Taiwan. Angiogenesis plays a critical role in tumor growth and metastasis processes and has relevance in disease recurrence, pelvic lymph node metastasis and poor prognosis. Cancer cells can produce several angiogenesis-stimulating factors involved in vascular growth, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and inflammatory cytokines such as interleukin (IL)-8. Common chemotherapeutic drugs for intravesical instillations usually cause major side effects, including urinary frequency, urinary urgency, cystitis, and hematuria. In order to identify a less cytotoxic therapeutic agent that can inhibit tumor cell proliferation, we examined the traditional Chinese herbal medicine Cortex Moutan—reported to have antibacterial, antiviral, anti-inflammatory, antithrombotic, and antitumor properties—for its effects on bladder cancer cell proliferation and expression of angiogenic factors. Our results revealed that Cortex Moutan exhibited high selectivity in inhibiting the growth of bladder cancer cells and also reduced the expression of angiogenesis-stimulating factors in those cells. Thus, we suggest that Cortex Moutan might be used as a cancer therapy drug for bladder’s intravesical chemotherapy in the future.展开更多
目的:采用网络药理学和分子对接探讨“知母-牡丹皮”治疗系统性红斑狼疮(SLE)的关键靶点及分子机制。方法:利用TCMSP数据库查找知母-牡丹皮中药物所含有的化学成分,通过GeneCards、OMIM、TTD、DrugBank和DisGeNET数据库检索SLE疾病的相...目的:采用网络药理学和分子对接探讨“知母-牡丹皮”治疗系统性红斑狼疮(SLE)的关键靶点及分子机制。方法:利用TCMSP数据库查找知母-牡丹皮中药物所含有的化学成分,通过GeneCards、OMIM、TTD、DrugBank和DisGeNET数据库检索SLE疾病的相应靶点,将药物与疾病的基因映射得到知母-牡丹皮治疗SLE的目标靶点;采用Cytoscape软件筛选核心靶点,构建知母-牡丹皮“中药—有效成分—靶点”网络。将交集靶点导入Metascape数据库进行GO、KEGG富集分析,利用Auto Dock Tools软件进行分子对接。结果:共得到出知母-牡丹皮16个活性成分,预测193个对应靶点,与SLE的3224个疾病靶点共有的靶点为127个,主要有效化合物为槲皮素、山柰酚、淫羊藿苷元、豆甾醇和薯蓣皂苷元等;目标靶点为AKT1、TNF、IL-6、VEGFA、TP53。KEGG共获得194条富集结果,GO共获得1877条。分子对接结果表明主要有效成分可以和目标靶点结合,结合构象稳定。结论:通过网络药理学验证了知母-牡丹皮多成分、多靶点、综合作用的特点,推测了知母-牡丹皮在SLE治疗中的可能作用机制,为其进一步研究提供理论依据。展开更多
文摘Moutan Cortex (MC) has been demonstrated to have an inhibitive effect on inflammation and oxidative stress responses in mesangial cells in our previous study. However, little is known about the components of MC contributing to this benefit. In the present study, cell membrane immobilized chromatography (CMC), a fast and useful method, was presented for screening potential active components of MC. HBZY-1 cells were incubated with MC (200 μg/mL) at the optimal incubation time (90 min). HPLC-DAD analysis and LC/ESI/MS/MS were performed to distinguish the active components and identify its structural ion fragments. The results showed that eight components binding to HBZY-1 cells were mudanoside B, paeoniflorin sulfonate, paeoniflorin, tetragalloyl glucose (isomeride), hexagalloyl glucose, mudanopiside A, and paeonol. In conclusion, our established CMC might be a useful method for screening potential active components in complicated traditional Chinese medicines. These components might be associated with the efficacy of MC on prevention and treatment of diabetic nephropathy.
基金supported by the Fund for Creative Research Groups of China,National Natural Science Foundation of China(No.81421005)the Specialized Research Fund of the Doctoral Program of Higher Education(SRFDP)+3 种基金Research Council Earmarked Research Grants(RCERG)(No.201300 96140001)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)partially supported by the National Natural Science Foundation of China(No.81274159)supported by New Century Excellent Talents in University(NCET-12-0976)
文摘The present study was designed to investigate the therapeutic effcts of Moutan Cortex(CM,root bark of Paeonia suffruticosa Andr) and Paeoniae Radix Rubra(PR,root of Paeonia veitchii Lynch) on metabolic disorders,focusing on the infuence of CM and PR on the obesity-related gut microbiota homeostasis.The diet-induced obese(DIO) mouse model was used to test the therapeutic effects of CM and PR.The mice were orally administered with CM and PR for 6 weeks,and oral glucose tolerance test(OGTT) and insulin tolerance test(ITT) were performed to evaluate the insulin sensitivity of the mice.Sterol-regulatory element binding proteins(SREBPs) and their target genes were measured by quantitative RT-PCR.High-throughput 16 S ribosomal RNA(16S rR NA) gene sequencing technology was used to determine the composition of gut microbiota,and the metabolites in serum were analyzed by GC-MS.Our results indicated that CM and PR combination alleviated obese and insulin resistance in the DIO mice,leading to increased glucose uptake and gene expression in muscle and liver,and down-regulated SREBPs and their target genes in liver.Interesting,neither the CM-PR extracts,nor the major components of CM and PR did not affect SREBPs activity in cultured cells.Meanwhile,CM and PR significantly modulated the gut microbiota of the high-fat diet(HFD) treated mice,similar to metformin,and CM-PR reversed the overall microbiota composition similar to the normal chow diet(NCD) treated mice.In conclusion,our results provide novel mechanisms of action for the effects of CM and PR in treating DIO-induced dysregulation of sugar and lipid metabolism.
文摘Objective: Establish a quick, precise and specific method to determine whether the moutan cortex obtained from market is processed with sulfur; provide a reliable method for the scientific evaluation.Methods: Three methods, including acid-base titration method, high-performance liquid-chromatography(HPLC) method, and ultraperformance liquid chromatography coupled with time-of-flight mass spectrometry(UHPLC-TOF-MS) method were used to detect whether30 batches of samples were fumigated with sulfur.Results: The results of three methods were substantially the same. Fifteen batches were identified to have been processed with sulfur fumigation, while others were not.Conclusions: The HPLC method was found to be most appropriate for the determination of sulfur fumigation for moutan cortex.
基金Special Fund for TCM by State Administration of Traditional Chinese Medicine of China(No.201507002-10)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-012)Construction of Liuwei Dihuang Capsule Standard(No.ZYBZH-C-JL-24-03)
文摘Objective To identify the quality markers of Moutan Cortex(MC) and establish the quality evaluation methods for multi-component assay and fingerprinting of MC. Methods The chemical constituents in MC were identified by HPLC-QTOF-MS. UPLC was employed for the multi-component assay and fingerprinting of MC. Furthermore, text mining was carried out to review the biosynthesis pathways and pharmacological and pharmacokinetic studies related to MC, and in silico target fishing was conducted to construct compound-target networks for MC. Results Sixteen compounds were clearly identified in MC and their structures were confirmed through comparison with literature data. In addition, the biosynthetic pathways and component specificities of the identified compounds were summarized and confirmed by text mining.Pharmacological activities, including traditional usage and modern pharmacological studies were summarized. A total of 282 targets from Homo sapiens were fished for 13 compounds. In addition, pharmacokinetic studies of different compounds were synopsized. Finally, multi-component assay and fingerprint of MC were established. Conclusion Eight major components are selected as quality markers of MC, such as oxypaeoniflorin, apiopaeonoside, albiflorin, paeonolide, paeoniflorin, 1,2,3,4,6-penta-O-galloyl-β-D-glucose, mudanpioside C and paeonol. These eight quality markers are successfully applied to the quality evaluation of MC, and could be useful in improving the current quality standards of MC.
文摘Cortex Moutan (Paeonia suffruticosa Andr.) is a common traditional Chinese medicine and has been widely used in clinic for 2000 years in China. As sources for this crude drug are always mixed with other species, many cultivars on herbal market may lead to quality instability. Multi-component quantitative analysis is an efficient method to reflect chemical profiles of herb medicine and is always taken as the main method for quality evaluation. So, the aim of this work is to develop analytical method to quantify paeonol, paeoniflorin, gallic acid, oxypaeoniflorin, benzoylpaeoniflorin and paeonolide in Cortex Moutan (CM) to evaluate the chemical qualities of CM from different species or cultivars. Besides, we also study the intestinal absorption characteristics of paeonol and paeoniflorin for further pharmacological evaluation. In the present study, all of the standard markers were performed on an Ecosil C18 (250 mm × 4.6 mm, 5 μM, Lubex Co., Guangzhou, China) with linear gradient elution of 0.2% formic acid water and acetonitrile. The proposed method was applied to analyze 50 batches of samples with acceptable linearity (R2, 0.9995 - 0.9999), precisions (RSD, 0.47% - 2.08%), repeatability (RSD, 039% - 2.63%), stability (RSD, 0.52% - 2.45%), and recovery (RSD, 0.72% - 3.03%) of the six compounds. Furthermore, the Hierarchical Cluster Analysis was applied to classify the 50 samples based on contents of the six compound markers. The results obtained from multi-component quantification of CM clearly indicated that CM originated from P. suffruticosa and P. ostii presented different chemical properties, and that samples from the two materials could be gathered into one branch, respectively, while CM sourced from cultivars of P. suffruticosa showed great variety on chemical quality. The results from Hierarchical Cluster Analysis implied that the established method could be used as a powerful tool for the quality evaluation of CM. The intestinal absorption study indicated that the intestinal absorption activities for paeoniflorin and paeonol showed an increasing absorption with time. Paeonol had lower absorption rate (6.69% - 15.93%) than that of paeoniflorin (19.0% - 30.70%). As a result, the established method is suitable for the quality evaluation of CM. The results of intestinal absorption characteristics of paeonol and paeoniflorin offer an insight for pharmacological evaluation and clinical efficacy research of CM.
基金Special scientific research project of the national traditional Chinese medicine clinical base business construction of state administration of traditional Chinese medicine(No.JDZX2015043)。
文摘Objective:To clarify the material basis of Chinese medicine pair“Radix Paeoniae Rubra-Cortex Moutan”(Chishao-Mudanpi)and explore their mechanism in the treatment of ICH with network pharmacology.Methods:The active ingredients contained in Radix Paeoniae Rubra and Cortex Moutan were searched and selected based on the oral bioavailability prediction and drug-likeness prediction from the TCMSP database.Then the targets of cerebral hemorrhage were collected from GeneCards,OMIM,and DrugBank databases.After obtained the intersections of drugs and disease,the active component target disease interactive network diagram was drawn by Cytoscape software.The obtained key targets were uploaded to the STRING database for analysis and construct a PPI network map.GO function enrichment analysis and KEGG analysis were performed on the key target proteins.Results:Collected the active ingredients of Radix Paeoniae 119,Radix Paeoniae 55,including paeoniflorin,baicalin,β-sitosterol,etc.Related drug target protein 1190,ICH disease-related genes 823,"Radix Paeoniae-Radix Paeoniae"and 72 common targets of ICH,mainly acting on Akt1,IL6,VEGFA,CASP3,EGF,involving 133 related signaling pathways such as AGE-RAGE,TNF,IL-17,HIF1,PI3K-Akt.Conclusion:The combination of"Radix Paeoniae Rubra-Cortex Moutan"in the treatment of ICH has the characteristics of multiple pathways and multiple targets,which provides a reference and basis for further molecular biology verification in the future.
文摘Metastases are the main cause of death among patients with bladder cancer, which is the second most common malignancy of the genitourinary tract and is highly prevalent in the southwestern region of Taiwan. Angiogenesis plays a critical role in tumor growth and metastasis processes and has relevance in disease recurrence, pelvic lymph node metastasis and poor prognosis. Cancer cells can produce several angiogenesis-stimulating factors involved in vascular growth, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and inflammatory cytokines such as interleukin (IL)-8. Common chemotherapeutic drugs for intravesical instillations usually cause major side effects, including urinary frequency, urinary urgency, cystitis, and hematuria. In order to identify a less cytotoxic therapeutic agent that can inhibit tumor cell proliferation, we examined the traditional Chinese herbal medicine Cortex Moutan—reported to have antibacterial, antiviral, anti-inflammatory, antithrombotic, and antitumor properties—for its effects on bladder cancer cell proliferation and expression of angiogenic factors. Our results revealed that Cortex Moutan exhibited high selectivity in inhibiting the growth of bladder cancer cells and also reduced the expression of angiogenesis-stimulating factors in those cells. Thus, we suggest that Cortex Moutan might be used as a cancer therapy drug for bladder’s intravesical chemotherapy in the future.
文摘目的:采用网络药理学和分子对接探讨“知母-牡丹皮”治疗系统性红斑狼疮(SLE)的关键靶点及分子机制。方法:利用TCMSP数据库查找知母-牡丹皮中药物所含有的化学成分,通过GeneCards、OMIM、TTD、DrugBank和DisGeNET数据库检索SLE疾病的相应靶点,将药物与疾病的基因映射得到知母-牡丹皮治疗SLE的目标靶点;采用Cytoscape软件筛选核心靶点,构建知母-牡丹皮“中药—有效成分—靶点”网络。将交集靶点导入Metascape数据库进行GO、KEGG富集分析,利用Auto Dock Tools软件进行分子对接。结果:共得到出知母-牡丹皮16个活性成分,预测193个对应靶点,与SLE的3224个疾病靶点共有的靶点为127个,主要有效化合物为槲皮素、山柰酚、淫羊藿苷元、豆甾醇和薯蓣皂苷元等;目标靶点为AKT1、TNF、IL-6、VEGFA、TP53。KEGG共获得194条富集结果,GO共获得1877条。分子对接结果表明主要有效成分可以和目标靶点结合,结合构象稳定。结论:通过网络药理学验证了知母-牡丹皮多成分、多靶点、综合作用的特点,推测了知母-牡丹皮在SLE治疗中的可能作用机制,为其进一步研究提供理论依据。