Abscract:OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog(PTEN) and meta...Abscract:OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog(PTEN) and metadherin(MTDH).METHODS Guizhi Fuling Wan(GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition,Wistar rats were given GFW viagavage at 4 g·kg^(-1)·d^(-1),8 g·kg^(-1)·d^(-1),16 g·kg^(-1)·d^(-1),or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera,medium-dose sear,highdose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells.Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells.RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera.RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli.taxel,the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold,respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec.tively;there was a significant difference between the groups(P<0.01).RT-qPCR results showed that,compared with the blank serum,the sera can up-regulate the expression of PTEN mRNA and downregulate the expression of MTDH mRNA in a dose-dependent manner.Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement.CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH,up-regulation of PTEN and induction of apoptosis,providing with an experiment basis for the applica.tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.展开更多
目的:对真武汤合桂枝茯苓丸加减联合常规药物治疗慢性心力衰竭的有效性进行系统评价。方法:系统检索中国知网、万方医学、维普、中国生物医学文献数据库、Pub Med、Cochrane Library、Web of Science、Embase数据库,收集真武汤合桂枝茯...目的:对真武汤合桂枝茯苓丸加减联合常规药物治疗慢性心力衰竭的有效性进行系统评价。方法:系统检索中国知网、万方医学、维普、中国生物医学文献数据库、Pub Med、Cochrane Library、Web of Science、Embase数据库,收集真武汤合桂枝茯苓丸加减治疗慢性心力衰竭的随机对照试验,搜索至2022年11月6日在库文章。由独立的2名研究者进行文献资料的筛选、资料的提取、评价纳入研究的偏倚风险后,采用Rev Man 5.3软件进行Meta分析。结果:7项纳入的随机对照试验,总样本量684例,其中试验组344例,对照组340例。Meta分析显示结果,治疗后试验组患者的临床综合疗效明显高于对照组,差异有统计学意义[比值比(OR)=4.77,95%置信区间(CI)(2.97,7.67),P<0.00001],降低血清B型脑钠肽水平[均数差(MD)=-70.90,95%CI(-122.89,-18.92),P=0.008]和血清N末端脑钠肽水平[MD=-0.66,95%CI(-1.27,-0.05),P=0.03],升高左心室射血分数[MD=4.64,95%CI(3.19,6.09),P<0.00001],降低左心室舒张末期内径[MD=-3.49,95%CI(-4.10,-2.88),P<0.00001],减少肿瘤坏死因子-α[MD=-4.05,95%CI(-6.18,-1.91),P=0.0002]和超敏C反应蛋白[MD=-2.23,95%CI(-2.99,-1.47),P<0.00001]。结论:当前证据显示,真武汤合桂枝茯苓丸联合常规药物治疗慢性心力衰竭具有较好的疗效,可以提高心功能,改善预后,效果优于单纯应用西药治疗。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。展开更多
目的:通过网络药理学的方法探讨桂枝茯苓丸治疗糖尿病肾病(Diabetic Nephropathy,DN)的信号通路及其可能的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analys...目的:通过网络药理学的方法探讨桂枝茯苓丸治疗糖尿病肾病(Diabetic Nephropathy,DN)的信号通路及其可能的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索桂枝茯苓丸中桂枝、茯苓、牡丹、赤芍、桃仁5味中药的有效活性成分,并用Perl软件得出药物作用靶基因,应用Uniprot数据库将药物靶点规范为相应的基因名称;在Genecards数据库、人类孟德尔遗传数据库中输入“diabetic nephropathy”,获取DN的疾病靶点基因。通过R软件获取药物-疾病的交集作用靶点,采用Cytoscape 3.2.1软件绘制成分-靶点-疾病可视化网络图,利用STRING数据库及Cytoscape 3.2.1软件得到靶点蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络图,并进一步对关键靶点进行基因本体论(Gene Ontology,GO)功能富集分析、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果:桂枝茯苓丸药物组成中活性成分有85个,药物靶点有100个,DN疾病靶点有3496个,通过R软件得到交集靶点68个,PPI网络图核心靶点为白细胞介素-6(Interleukin-6,IL-6)、血管内皮生长因子(Vascular Endothelial Growth Factor A,VEGF)A、丝裂原激活蛋白激酶8(Mitogen-Activated Protein Kinase 8,MAPK8)等。GO功能富集分析主要涉及DNA结合转录因子、RNA聚合酶Ⅱ、血红素结合、泛素样蛋白连接酶结合、转录因子结合、核受体活性等。KEGG通路富集分析显示主要涉及流体剪应力与动脉粥样硬化、晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Receptor For Advanced Glycation End Products,RAGE)、细胞凋亡、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1信号通路等。结论:桂枝茯苓丸可能通过多成分、多靶点、多通路实现治疗DN的作用。展开更多
目的:运用网络药理学和分子对接探讨桂枝茯苓丸合芍药甘草汤治疗糖尿病周围神经病变(Diabetic Peripheral Neuropathy,DPN)的作用机制。方法:运用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Da...目的:运用网络药理学和分子对接探讨桂枝茯苓丸合芍药甘草汤治疗糖尿病周围神经病变(Diabetic Peripheral Neuropathy,DPN)的作用机制。方法:运用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、DrugBank、UniProt、GeneCards、OMIM、TTD数据库预测和筛选出活性成分和靶点。运用Metascape进行基因本体论(Gene Ontology,GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。运用String 11.0和Cytoscape 3.7.2构建蛋白质-蛋白质相互作用(Protein-Protein Interaction,PPI)网络和活性成分-靶点网络图,并进行分子对接验证。结果:筛选得到桂枝茯苓丸合芍药甘草汤治疗DPN的活性成分123 个、靶点149 个、通路96 个。其可能主要通过槲皮素、山奈酚、和黄芩素等13 个核心成分作用于信号传导蛋白和转录激活物(STAT3)、AP-1 转录因子(JUN)、丝氨酸/ 苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、肿瘤抑制蛋白(TP53)、丝裂原活化蛋白激酶3(MAPK3)、丝裂原活化蛋白激酶1(MAPK1)等7 个核心靶点,从而调控晚期糖基化终末产物- 糖基化终末产物受体(AGE-RAGE)、磷脂酰肌醇3 激酶- 蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)等关键通路,从而发挥治疗的作用。结论:桂枝茯苓丸合芍药甘草汤通过多成分、多靶点、多通路实现干预DPN 治疗的作用,为进一步的临床和实验研究提供了新思路。展开更多
基金supported by Natural Science Foundation of Henan Province (162300410204)
文摘Abscract:OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog(PTEN) and metadherin(MTDH).METHODS Guizhi Fuling Wan(GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition,Wistar rats were given GFW viagavage at 4 g·kg^(-1)·d^(-1),8 g·kg^(-1)·d^(-1),16 g·kg^(-1)·d^(-1),or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera,medium-dose sear,highdose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells.Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells.RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera.RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli.taxel,the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold,respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec.tively;there was a significant difference between the groups(P<0.01).RT-qPCR results showed that,compared with the blank serum,the sera can up-regulate the expression of PTEN mRNA and downregulate the expression of MTDH mRNA in a dose-dependent manner.Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement.CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH,up-regulation of PTEN and induction of apoptosis,providing with an experiment basis for the applica.tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.
文摘目的:对真武汤合桂枝茯苓丸加减联合常规药物治疗慢性心力衰竭的有效性进行系统评价。方法:系统检索中国知网、万方医学、维普、中国生物医学文献数据库、Pub Med、Cochrane Library、Web of Science、Embase数据库,收集真武汤合桂枝茯苓丸加减治疗慢性心力衰竭的随机对照试验,搜索至2022年11月6日在库文章。由独立的2名研究者进行文献资料的筛选、资料的提取、评价纳入研究的偏倚风险后,采用Rev Man 5.3软件进行Meta分析。结果:7项纳入的随机对照试验,总样本量684例,其中试验组344例,对照组340例。Meta分析显示结果,治疗后试验组患者的临床综合疗效明显高于对照组,差异有统计学意义[比值比(OR)=4.77,95%置信区间(CI)(2.97,7.67),P<0.00001],降低血清B型脑钠肽水平[均数差(MD)=-70.90,95%CI(-122.89,-18.92),P=0.008]和血清N末端脑钠肽水平[MD=-0.66,95%CI(-1.27,-0.05),P=0.03],升高左心室射血分数[MD=4.64,95%CI(3.19,6.09),P<0.00001],降低左心室舒张末期内径[MD=-3.49,95%CI(-4.10,-2.88),P<0.00001],减少肿瘤坏死因子-α[MD=-4.05,95%CI(-6.18,-1.91),P=0.0002]和超敏C反应蛋白[MD=-2.23,95%CI(-2.99,-1.47),P<0.00001]。结论:当前证据显示,真武汤合桂枝茯苓丸联合常规药物治疗慢性心力衰竭具有较好的疗效,可以提高心功能,改善预后,效果优于单纯应用西药治疗。受纳入研究数量和质量的限制,上述结论尚待更多高质量研究予以验证。
文摘目的:通过网络药理学的方法探讨桂枝茯苓丸治疗糖尿病肾病(Diabetic Nephropathy,DN)的信号通路及其可能的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索桂枝茯苓丸中桂枝、茯苓、牡丹、赤芍、桃仁5味中药的有效活性成分,并用Perl软件得出药物作用靶基因,应用Uniprot数据库将药物靶点规范为相应的基因名称;在Genecards数据库、人类孟德尔遗传数据库中输入“diabetic nephropathy”,获取DN的疾病靶点基因。通过R软件获取药物-疾病的交集作用靶点,采用Cytoscape 3.2.1软件绘制成分-靶点-疾病可视化网络图,利用STRING数据库及Cytoscape 3.2.1软件得到靶点蛋白质-蛋白质相互作用(Protein-protein Interaction,PPI)网络图,并进一步对关键靶点进行基因本体论(Gene Ontology,GO)功能富集分析、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果:桂枝茯苓丸药物组成中活性成分有85个,药物靶点有100个,DN疾病靶点有3496个,通过R软件得到交集靶点68个,PPI网络图核心靶点为白细胞介素-6(Interleukin-6,IL-6)、血管内皮生长因子(Vascular Endothelial Growth Factor A,VEGF)A、丝裂原激活蛋白激酶8(Mitogen-Activated Protein Kinase 8,MAPK8)等。GO功能富集分析主要涉及DNA结合转录因子、RNA聚合酶Ⅱ、血红素结合、泛素样蛋白连接酶结合、转录因子结合、核受体活性等。KEGG通路富集分析显示主要涉及流体剪应力与动脉粥样硬化、晚期糖基化终末产物(Advanced Glycation End Products,AGE)-晚期糖基化终末产物受体(Receptor For Advanced Glycation End Products,RAGE)、细胞凋亡、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1信号通路等。结论:桂枝茯苓丸可能通过多成分、多靶点、多通路实现治疗DN的作用。
