Objective:The purpose of this study is to investigate the anti-diabetic effects of linarin,a flavonoid extracted from Chrysanthemi Indici Flos(CIF),and its potential mechanisms.Methods:The effects of linarin on cell v...Objective:The purpose of this study is to investigate the anti-diabetic effects of linarin,a flavonoid extracted from Chrysanthemi Indici Flos(CIF),and its potential mechanisms.Methods:The effects of linarin on cell viability and glucose consumption in Hep G2 cells were measured.Meanwhile,monosodium glutamate(MSG) mouse model was constructed to monitor the changes of insulin tolerance,glucose tolerance,triglyceride and cholesterol.The protein expression levels of pAMPK,p-ACC,PEPCK and p-GS were detected by Western blot.Results:Linarin could increase the relative glucose consumption of Hep G2 cells,improve insulin tolerance and glucose tolerance,and decrease the levels of triglyceride and cholesterol of MSG mice.Simultaneously,the expression levels of p-AMPK and p-ACC in Hep G2 cells and the liver tissue of MSG mice were increased,while the expression levels of PEPCK and p-GS were decreased after treatment with linarin.Conclusion:Insulin resistance could be ameliorated by linarin in type 2 diabetes,and its mechanism may be related to AMPK signaling pathway.展开更多
目的:基于网络药理学探究枸杞子-菊花药对治疗糖尿病视网膜病变(diabetic retinopathy, DR)的干预机制。方法:利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,...目的:基于网络药理学探究枸杞子-菊花药对治疗糖尿病视网膜病变(diabetic retinopathy, DR)的干预机制。方法:利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)检索枸杞子、菊花的活性成分及相关靶点。利用Cytoscape 3.9.1绘制“药对-活性成分-作用靶点”网络图,并进行拓扑分析筛选枸杞子-菊花药对治疗DR的主要活性成分。利用GeneCards数据库、在线人类孟德尔遗传数据库及药物靶标数据库检索DR相关靶点。将活性成分相关靶点与疾病靶点导入Venny 2.1在线平台,绘制韦恩图,交集靶点即为枸杞子-菊花药对治疗DR的潜在靶点。将潜在靶点上传至STRING数据库构建PPI网络关系,导入Cytoscape 3.9.1软件进行可视化,PPI网络拓扑分析筛选枸杞子-菊花药对治疗DR的核心靶点。将核心靶点输入Metascape在线平台进行基因本体(gene ontology, GO)富集分析及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)信号通路富集分析。将活性成分、核心靶点、信号通路导入Cytoscape 3.9.1软件构建“活性成分-作用靶点-信号通路-DR”网络图。结果:利用TCMSP数据库得到52种活性成分及247个相关靶点。“枸杞子菊花药对-活性成分-作用靶点”网络分析筛选出槲皮素、β-谷甾醇、山柰酚等为枸杞子-菊花药对治疗DR的主要活性成分。检索得到DR相关靶点2 347个,枸杞子-菊花药对治疗DR的潜在靶点133个。PPI网络分析筛选出蛋白激酶Bα(protein kinase Bα,AKT1)、半胱氨酸天冬氨酸蛋白酶3(caspase-3,CASP3)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)等为核心靶点。GO富集分析得到生物过程919个、细胞组分23个、分子功能47个。KEGG信号通路富集分析得到134条信号通路。“活性成分-作用靶点-信号通路-DR”网络分析发现枸杞子-菊花药对通过槲皮素、β-谷甾醇、山柰酚等活性成分作用于PTGS2、CASP3、AKT1等靶点调控糖尿病并发症中的AGE-RAGE信号通路、IL-17信号通路、TNF信号通路、PI3K-AKT信号通路、MAPK信号通路等进而改善DR。结论:枸杞子-菊花药对通过多成分、多靶点、多通路作用于DR。展开更多
目的观察野菊花提取物对糖尿病KKAy小鼠血糖和血脂水平的影响,及对醛糖还原酶(AR)的抑制作用。方法 8周龄雄性KKAy小鼠,根据初始空腹血糖随机分为模型组、野菊花提取物20和100 mg·kg^(-1)组及格列美脲0.4 mg·kg^(-1)组,以雄性...目的观察野菊花提取物对糖尿病KKAy小鼠血糖和血脂水平的影响,及对醛糖还原酶(AR)的抑制作用。方法 8周龄雄性KKAy小鼠,根据初始空腹血糖随机分为模型组、野菊花提取物20和100 mg·kg^(-1)组及格列美脲0.4 mg·kg^(-1)组,以雄性C57BL/6J小鼠作为正常对照组,每天ig给药1次,连续7周。每周测量小鼠体质量和摄食量,实验结束前测定空腹血糖并进行口服葡萄糖耐量实验(OGTT)。末次给药后禁食过夜,处死小鼠,取血清进行生化检测,ELISA测定血清中胰岛素、瘦素和AR水平,解剖取肝、肾、脾、睾周脂肪和肾周脂肪,测定脏器系数并进行常规病理组织学检查。实时PCR测定肾组织匀浆中AR m RNA表达。结果与模型组比较,野菊花提取物100 mg·kg^(-1)组小鼠摄食量明显减少(P<0.01),空腹血糖明显降低(P<0.05);OGTT结果表明野菊花提取物可显著抑制葡萄糖吸收(P<0.01),血清谷丙转氨酶、葡萄糖、甘油三酯、胆固醇、低密度脂蛋白胆固醇、胰岛素、瘦素和AR水平明显降低(P<0.05,P<0.01)。组织病理学观察显示,模型组小鼠肝、肾、脂肪、胰腺和脾组织出现不同程度病变,野菊花提取物可抑制糖尿病引起的组织病理变化;同时可降低肾组织AR m RNA表达。结论野菊花提取物对KKAy小鼠有降血糖和血脂的作用,并能保护因糖尿病引起的肾、肝、脂肪、胰腺和脾损伤,其对肾的保护作用与降低肾组织AR m RNA表达从而抑制AR作用有关。展开更多
基金supported by the National Natural Science Foundation of China (grant numbers 81273392)the Natural Science Foundation of Henan Province (grant numbers 182300410348)
文摘Objective:The purpose of this study is to investigate the anti-diabetic effects of linarin,a flavonoid extracted from Chrysanthemi Indici Flos(CIF),and its potential mechanisms.Methods:The effects of linarin on cell viability and glucose consumption in Hep G2 cells were measured.Meanwhile,monosodium glutamate(MSG) mouse model was constructed to monitor the changes of insulin tolerance,glucose tolerance,triglyceride and cholesterol.The protein expression levels of pAMPK,p-ACC,PEPCK and p-GS were detected by Western blot.Results:Linarin could increase the relative glucose consumption of Hep G2 cells,improve insulin tolerance and glucose tolerance,and decrease the levels of triglyceride and cholesterol of MSG mice.Simultaneously,the expression levels of p-AMPK and p-ACC in Hep G2 cells and the liver tissue of MSG mice were increased,while the expression levels of PEPCK and p-GS were decreased after treatment with linarin.Conclusion:Insulin resistance could be ameliorated by linarin in type 2 diabetes,and its mechanism may be related to AMPK signaling pathway.
文摘目的:基于网络药理学探究枸杞子-菊花药对治疗糖尿病视网膜病变(diabetic retinopathy, DR)的干预机制。方法:利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)检索枸杞子、菊花的活性成分及相关靶点。利用Cytoscape 3.9.1绘制“药对-活性成分-作用靶点”网络图,并进行拓扑分析筛选枸杞子-菊花药对治疗DR的主要活性成分。利用GeneCards数据库、在线人类孟德尔遗传数据库及药物靶标数据库检索DR相关靶点。将活性成分相关靶点与疾病靶点导入Venny 2.1在线平台,绘制韦恩图,交集靶点即为枸杞子-菊花药对治疗DR的潜在靶点。将潜在靶点上传至STRING数据库构建PPI网络关系,导入Cytoscape 3.9.1软件进行可视化,PPI网络拓扑分析筛选枸杞子-菊花药对治疗DR的核心靶点。将核心靶点输入Metascape在线平台进行基因本体(gene ontology, GO)富集分析及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)信号通路富集分析。将活性成分、核心靶点、信号通路导入Cytoscape 3.9.1软件构建“活性成分-作用靶点-信号通路-DR”网络图。结果:利用TCMSP数据库得到52种活性成分及247个相关靶点。“枸杞子菊花药对-活性成分-作用靶点”网络分析筛选出槲皮素、β-谷甾醇、山柰酚等为枸杞子-菊花药对治疗DR的主要活性成分。检索得到DR相关靶点2 347个,枸杞子-菊花药对治疗DR的潜在靶点133个。PPI网络分析筛选出蛋白激酶Bα(protein kinase Bα,AKT1)、半胱氨酸天冬氨酸蛋白酶3(caspase-3,CASP3)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)等为核心靶点。GO富集分析得到生物过程919个、细胞组分23个、分子功能47个。KEGG信号通路富集分析得到134条信号通路。“活性成分-作用靶点-信号通路-DR”网络分析发现枸杞子-菊花药对通过槲皮素、β-谷甾醇、山柰酚等活性成分作用于PTGS2、CASP3、AKT1等靶点调控糖尿病并发症中的AGE-RAGE信号通路、IL-17信号通路、TNF信号通路、PI3K-AKT信号通路、MAPK信号通路等进而改善DR。结论:枸杞子-菊花药对通过多成分、多靶点、多通路作用于DR。
文摘目的观察野菊花提取物对糖尿病KKAy小鼠血糖和血脂水平的影响,及对醛糖还原酶(AR)的抑制作用。方法 8周龄雄性KKAy小鼠,根据初始空腹血糖随机分为模型组、野菊花提取物20和100 mg·kg^(-1)组及格列美脲0.4 mg·kg^(-1)组,以雄性C57BL/6J小鼠作为正常对照组,每天ig给药1次,连续7周。每周测量小鼠体质量和摄食量,实验结束前测定空腹血糖并进行口服葡萄糖耐量实验(OGTT)。末次给药后禁食过夜,处死小鼠,取血清进行生化检测,ELISA测定血清中胰岛素、瘦素和AR水平,解剖取肝、肾、脾、睾周脂肪和肾周脂肪,测定脏器系数并进行常规病理组织学检查。实时PCR测定肾组织匀浆中AR m RNA表达。结果与模型组比较,野菊花提取物100 mg·kg^(-1)组小鼠摄食量明显减少(P<0.01),空腹血糖明显降低(P<0.05);OGTT结果表明野菊花提取物可显著抑制葡萄糖吸收(P<0.01),血清谷丙转氨酶、葡萄糖、甘油三酯、胆固醇、低密度脂蛋白胆固醇、胰岛素、瘦素和AR水平明显降低(P<0.05,P<0.01)。组织病理学观察显示,模型组小鼠肝、肾、脂肪、胰腺和脾组织出现不同程度病变,野菊花提取物可抑制糖尿病引起的组织病理变化;同时可降低肾组织AR m RNA表达。结论野菊花提取物对KKAy小鼠有降血糖和血脂的作用,并能保护因糖尿病引起的肾、肝、脂肪、胰腺和脾损伤,其对肾的保护作用与降低肾组织AR m RNA表达从而抑制AR作用有关。