Background:Green tea,mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time,but their synergistic hypoglycemic effects and mechanisms remain unclear...Background:Green tea,mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time,but their synergistic hypoglycemic effects and mechanisms remain unclear.Methods:The effective components of green tea,mulberry leaf and corn silk were extracted and enriched.Mixture design of experiments was used to study the influences of different combinations on the cell viability and glucose uptake level of L6 myoblasts,so as to determine the optimal synergistic hypoglycemic combination.The possible hypoglycemic mechanism of the optimal synergistic combination was explored by cytotoxicity assay,glucose uptake assay,and western blot.Results:Three polyphenol enrichment fractions of the herbs,30%ethanol elution fraction of green tea(GT),50%ethanol elution fraction of mulberry leaf(ML)and 60%ethanol elution fraction of corn silk(CS)were obtained.The antioxidant activities of GT-30%,ML-50%and CS-60%were superior to those of crude extracts,and showed strong potential inα-amylase andα-glucosidase inhibition activities.The optimal synergistic combination of crude extracts G7(crude extract of green tea:crude extract of mulberry leaf:crude extract of corn silk=1:5:3),polyphenol enrichment fractions R3(GT-30%:ML-50%:CS-60%=1:7:1)and monomers X2(epigallocatechin gallate:morusin:formononetin=3:1:2)were selected,respectively.G7,R3,and X2 showed promoting effects on the cell viability and glucose uptake of L6 myoblasts within the detected concentration range.In addition,G7,R3,and X2 could increase the expression levels of p-PI3K/PI3K and p-Akt/Akt in L6 myoblasts,and promote the translocation of Glut4,but G7 and R3 showed more significant effects.Conclusion:The synergistic hypoglycemic effects of green tea,mulberry leaf and corn silk had the characteristics of multiple-components and multiple-targets with p-PI3K/PI3K,p-Akt/Akt and the translocation of Glut4 signal pathways involved.The three traditional herbs might have the potential to be combined used for the prevention and treatment of diabetes based on the synergistic hypoglycemic effects.展开更多
Type 2 diabetes is the most common type of diabetes. Conventionally many drugs are used for the treatment of diabetes such as biguanides, sulfonylureas, meglitinides, etc. But the desired effective treatment is still ...Type 2 diabetes is the most common type of diabetes. Conventionally many drugs are used for the treatment of diabetes such as biguanides, sulfonylureas, meglitinides, etc. But the desired effective treatment is still not to be achieved. So researches are going on for the development of effective alternative therapy against diabetes. Olive leaves are traditionally used in the treatment of the disease. However, studies on its mechanism of action are not yet enough. The aim of this study was to investigate whether olive leaf extract (OLE) improves insulin receptor substrate-1 (IRS-1), tyrosine kinase (TK), GLUT-2, and GLUT-4. Oleuropein levels were analyzed from OLE obtained by using four different solvents, and the highest content of methanol extract was selected for the study. Different concentrations of OLE (2.5 to 320 μg/mL) were incubated with hepatocellular carcinoma (HepG2) cells for 24 hours. After incubation, cell viability was assessed based on luminometric ATP cell viability assay kit. Intracellular reactive oxygen species (ROS) generating level was detected using 2,7dichlorodihydrofluorescein-diacetate (H2DCF-DA) fluorescent probes. Apoptosis was evaluated by acridine orange/ethidium bromide double staining method. Genotoxicity was evaluated by alkaline single cell gel electrophoresis assay (Comet Assay). Protein expression levels of IRS-1, TK, GLUT-2, and GLUT-4 were analyzed by western blotting technique from the obtained cell lysates. Although an optimum doses of OLE (10 μg/mL) maximally increased cell proliferation, decreased ROS generation improved IRS-1, TK, GLUT-2, and GLUT-4 protein expression levels (about fivefold), higher doses (10 to 320 μg/mL) markedly decreased the cell viability, increased DNA damage, apoptosis and ROS generation in a concentration-dependent manner. OLE can be used in the treatment of type 2 diabetes. However, in order to find the most effective and non-toxic concentration, dose optimization is required.展开更多
目的基于网络药理学探讨中药枇杷叶治疗糖尿病的作用机制。方法通过中药系统药理学数据库和分析平台(traditional Chinese medicine system pharmacology database and analysis platform,TCMSP)筛选出枇杷叶的有效成分,使用人类基因数...目的基于网络药理学探讨中药枇杷叶治疗糖尿病的作用机制。方法通过中药系统药理学数据库和分析平台(traditional Chinese medicine system pharmacology database and analysis platform,TCMSP)筛选出枇杷叶的有效成分,使用人类基因数据库(Gene Cards)获得糖尿病相关基因,采用Cytoscape3.7.1软件,构建"药物-成分-靶点-疾病"网络图,借助STRING数据库平台构建蛋白质相互作用网络(protein-to-protein interaction,PPI),利用Bioconductor平台对关键靶基因进行基因本体(gene ontology,GO)功能富集分析和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。结果枇杷叶可能通过槲皮素、表没食子儿茶素没食子酸酯(EGCG)、山奈酚等活性成分作用于IL6、CASP3、EGFR、VEGFA等关键靶点,通过MAPK信号通路、PI3K-Akt信号通路、AMPK信号通路等相关通路,参与DNA结合转录激活活性和RNA聚合酶Ⅱ特异性、核受体活性、转录因子活性和直接配体调节的序列特异性DNA结合、RNA聚合酶Ⅱ转录因子结合、核激素受体结合等生物学过程,达到治疗糖尿病的作用。结论通过构建"药物-成分-靶点-疾病"网络,从多成分、多靶点、多通路阐释枇杷叶治疗糖尿病的作用机制,为后续研究提供理论依据及新思路。展开更多
目的探讨中药六味地黄软胶囊和银杏叶片对2型糖尿病患者血清受活化调节、由正常T细胞表达和分泌的趋化蛋白(regulated upon activation,normal T-cell expressed and secreted,RANTES)水平的影响。方法在西药降糖治疗基础上,40例早期2...目的探讨中药六味地黄软胶囊和银杏叶片对2型糖尿病患者血清受活化调节、由正常T细胞表达和分泌的趋化蛋白(regulated upon activation,normal T-cell expressed and secreted,RANTES)水平的影响。方法在西药降糖治疗基础上,40例早期2型糖尿病患者,随机分为中药组和安慰剂组,每组20例,分别给予六味地黄软胶囊及银杏叶片或安慰剂治疗6个月,检测治疗前后血清RANTES、血糖、血脂、糖化血红蛋白及尿微量白蛋白水平。结果中药组治疗后血清RANTES较治疗前明显下降,且明显低于安慰剂组(P<0.05)。结论六味地黄软胶囊及银杏叶片可降低2型糖尿病患者血清RANTES水平,可能通过抗炎机制防治糖尿病并发症。展开更多
基金the grant from National Key Research and Development Program of China(Grant No.2021YFE0110000)the grant from Tianjin Municipal Science and Technology Foundation(Grant No.22JCYBJC00160).
文摘Background:Green tea,mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time,but their synergistic hypoglycemic effects and mechanisms remain unclear.Methods:The effective components of green tea,mulberry leaf and corn silk were extracted and enriched.Mixture design of experiments was used to study the influences of different combinations on the cell viability and glucose uptake level of L6 myoblasts,so as to determine the optimal synergistic hypoglycemic combination.The possible hypoglycemic mechanism of the optimal synergistic combination was explored by cytotoxicity assay,glucose uptake assay,and western blot.Results:Three polyphenol enrichment fractions of the herbs,30%ethanol elution fraction of green tea(GT),50%ethanol elution fraction of mulberry leaf(ML)and 60%ethanol elution fraction of corn silk(CS)were obtained.The antioxidant activities of GT-30%,ML-50%and CS-60%were superior to those of crude extracts,and showed strong potential inα-amylase andα-glucosidase inhibition activities.The optimal synergistic combination of crude extracts G7(crude extract of green tea:crude extract of mulberry leaf:crude extract of corn silk=1:5:3),polyphenol enrichment fractions R3(GT-30%:ML-50%:CS-60%=1:7:1)and monomers X2(epigallocatechin gallate:morusin:formononetin=3:1:2)were selected,respectively.G7,R3,and X2 showed promoting effects on the cell viability and glucose uptake of L6 myoblasts within the detected concentration range.In addition,G7,R3,and X2 could increase the expression levels of p-PI3K/PI3K and p-Akt/Akt in L6 myoblasts,and promote the translocation of Glut4,but G7 and R3 showed more significant effects.Conclusion:The synergistic hypoglycemic effects of green tea,mulberry leaf and corn silk had the characteristics of multiple-components and multiple-targets with p-PI3K/PI3K,p-Akt/Akt and the translocation of Glut4 signal pathways involved.The three traditional herbs might have the potential to be combined used for the prevention and treatment of diabetes based on the synergistic hypoglycemic effects.
基金funded by the Bezmialem Vakif University Scientific Research Projects Unit(No:6.2016/57).
文摘Type 2 diabetes is the most common type of diabetes. Conventionally many drugs are used for the treatment of diabetes such as biguanides, sulfonylureas, meglitinides, etc. But the desired effective treatment is still not to be achieved. So researches are going on for the development of effective alternative therapy against diabetes. Olive leaves are traditionally used in the treatment of the disease. However, studies on its mechanism of action are not yet enough. The aim of this study was to investigate whether olive leaf extract (OLE) improves insulin receptor substrate-1 (IRS-1), tyrosine kinase (TK), GLUT-2, and GLUT-4. Oleuropein levels were analyzed from OLE obtained by using four different solvents, and the highest content of methanol extract was selected for the study. Different concentrations of OLE (2.5 to 320 μg/mL) were incubated with hepatocellular carcinoma (HepG2) cells for 24 hours. After incubation, cell viability was assessed based on luminometric ATP cell viability assay kit. Intracellular reactive oxygen species (ROS) generating level was detected using 2,7dichlorodihydrofluorescein-diacetate (H2DCF-DA) fluorescent probes. Apoptosis was evaluated by acridine orange/ethidium bromide double staining method. Genotoxicity was evaluated by alkaline single cell gel electrophoresis assay (Comet Assay). Protein expression levels of IRS-1, TK, GLUT-2, and GLUT-4 were analyzed by western blotting technique from the obtained cell lysates. Although an optimum doses of OLE (10 μg/mL) maximally increased cell proliferation, decreased ROS generation improved IRS-1, TK, GLUT-2, and GLUT-4 protein expression levels (about fivefold), higher doses (10 to 320 μg/mL) markedly decreased the cell viability, increased DNA damage, apoptosis and ROS generation in a concentration-dependent manner. OLE can be used in the treatment of type 2 diabetes. However, in order to find the most effective and non-toxic concentration, dose optimization is required.
文摘目的基于网络药理学探讨中药枇杷叶治疗糖尿病的作用机制。方法通过中药系统药理学数据库和分析平台(traditional Chinese medicine system pharmacology database and analysis platform,TCMSP)筛选出枇杷叶的有效成分,使用人类基因数据库(Gene Cards)获得糖尿病相关基因,采用Cytoscape3.7.1软件,构建"药物-成分-靶点-疾病"网络图,借助STRING数据库平台构建蛋白质相互作用网络(protein-to-protein interaction,PPI),利用Bioconductor平台对关键靶基因进行基因本体(gene ontology,GO)功能富集分析和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。结果枇杷叶可能通过槲皮素、表没食子儿茶素没食子酸酯(EGCG)、山奈酚等活性成分作用于IL6、CASP3、EGFR、VEGFA等关键靶点,通过MAPK信号通路、PI3K-Akt信号通路、AMPK信号通路等相关通路,参与DNA结合转录激活活性和RNA聚合酶Ⅱ特异性、核受体活性、转录因子活性和直接配体调节的序列特异性DNA结合、RNA聚合酶Ⅱ转录因子结合、核激素受体结合等生物学过程,达到治疗糖尿病的作用。结论通过构建"药物-成分-靶点-疾病"网络,从多成分、多靶点、多通路阐释枇杷叶治疗糖尿病的作用机制,为后续研究提供理论依据及新思路。
文摘目的探讨中药六味地黄软胶囊和银杏叶片对2型糖尿病患者血清受活化调节、由正常T细胞表达和分泌的趋化蛋白(regulated upon activation,normal T-cell expressed and secreted,RANTES)水平的影响。方法在西药降糖治疗基础上,40例早期2型糖尿病患者,随机分为中药组和安慰剂组,每组20例,分别给予六味地黄软胶囊及银杏叶片或安慰剂治疗6个月,检测治疗前后血清RANTES、血糖、血脂、糖化血红蛋白及尿微量白蛋白水平。结果中药组治疗后血清RANTES较治疗前明显下降,且明显低于安慰剂组(P<0.05)。结论六味地黄软胶囊及银杏叶片可降低2型糖尿病患者血清RANTES水平,可能通过抗炎机制防治糖尿病并发症。
