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
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
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
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
The chemical constituents of Cortex Moutan charcoal were studied in depth, and their coagulation activity was screened. The chemical constituents were isolated by polyamide, silica gel and Sephadex G-Sepharose chromat...The chemical constituents of Cortex Moutan charcoal were studied in depth, and their coagulation activity was screened. The chemical constituents were isolated by polyamide, silica gel and Sephadex G-Sepharose chromatography purification, and their structures were identified by NMR spectroscopy and other analyses. A total of 10 compounds were obtained and identified as follows： 3-（2-furan）-l-（2-hydroxy-4-methoxy-phenyl）-2-propylene ketone （1）, 2-（2,5-hydroxy-4-methyl phenyl） propionate ethyl ester （2）, methyl tetradec-5-enoate （3）, 1,4-diethylcyclohexane （4）, catechol （5）, methyl-4-hydroxybenzoate （6）, 3-hydroxy- 2-methyl-4-pyrone （7）, 3,8-dihydroxy-2-metyl-chromone （8）, 3β-hydroxy-olean-12-en （9）, 1-monolinolein （10）. Among them, compounds 1 and 2 were new natural products, and 3-10 were isolated from the Cortex Moutan charcoal for the first time. The potential coagulation activities of compounds were evaluated, and compounds 2, 9 and 10 had strong hemostatic effects. While compounds 1 and 8 could significantly activate blood circulation.展开更多
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
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.
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.
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.
基金National Natural Science Foundation of China(Grant No.81473352)Guangdong Province Innovation Training Project(Grant No.201610573040)Guangzhou Science and Technology Bureau Foundation(Grant No.201707010170)
文摘The chemical constituents of Cortex Moutan charcoal were studied in depth, and their coagulation activity was screened. The chemical constituents were isolated by polyamide, silica gel and Sephadex G-Sepharose chromatography purification, and their structures were identified by NMR spectroscopy and other analyses. A total of 10 compounds were obtained and identified as follows： 3-（2-furan）-l-（2-hydroxy-4-methoxy-phenyl）-2-propylene ketone （1）, 2-（2,5-hydroxy-4-methyl phenyl） propionate ethyl ester （2）, methyl tetradec-5-enoate （3）, 1,4-diethylcyclohexane （4）, catechol （5）, methyl-4-hydroxybenzoate （6）, 3-hydroxy- 2-methyl-4-pyrone （7）, 3,8-dihydroxy-2-metyl-chromone （8）, 3β-hydroxy-olean-12-en （9）, 1-monolinolein （10）. Among them, compounds 1 and 2 were new natural products, and 3-10 were isolated from the Cortex Moutan charcoal for the first time. The potential coagulation activities of compounds were evaluated, and compounds 2, 9 and 10 had strong hemostatic effects. While compounds 1 and 8 could significantly activate blood circulation.
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.
