Objective:To explore the potential active components,therapeutic targets and critical path of Alpinia officinarum and Pogostemonis Herba in the treatment of diabetic gastroparesis(DGP)by using network pharmacology.Met...Objective:To explore the potential active components,therapeutic targets and critical path of Alpinia officinarum and Pogostemonis Herba in the treatment of diabetic gastroparesis(DGP)by using network pharmacology.Methods:The main chemical components and corresponding targets genes of A.officinarum-Pogostemonis Herba were screened through TCMSP database retrieval[oral bioavailability(OB)≥30%and drug like(DL)≥0.18].Tgenes of diabetic gastroparesis were screened by the Human Gene Database(GeneCards),and Venny 2.1 software was used to obtained common targets for the active ingredients of A.officinarum-Pogostemonis Herba and DGP.Then,the protein-protein interaction(PPI)network of the common targets was constructed by STRING database and analyzed to performed the core targets.GO function and KEGG pathway enrichment analysis of the common target genes were obtained by using ClusterProfiler R package.Finally,the network diagram of"active ingredient-pathway-target"was used to establish by Cytoscape 3.8 software.Results:Totally 23 ingredients of A.officinarum-Pogostemonis Herba,97 active ingredients targets and 533 DGP related targets,including 46 common targets were selected.The common targets were mainly enriched in the cell constituents such as the nuclear chromatin and mitochondria outer membrane,involved in the biological processes as oxidative stress,apoptosis signal regulation,and molecular functions as enzyme binding,protein phosphatase binding,and cytokine activity.They were also concentrated in the signal pathways such as PI3K/Akt,HIF-1 and MAPK.The network of“active ingredients-targets-pathways”indicated the active components such as quercetin,kaempferol and galangin in A.officinarum-Pogostemonis Herba played an anti-delayed gastric emptying in diabetic gastroparesis by acting on PTGS2,NOS2,BCL2,IL6,VEGFA and other targets to jointly regulate PI3K-Akt,HIF-1 and MAPK pathways.Conclusion:This study initially reveals that the combined treatment of A.officinarum-Pogostemonis Herba for delayed gastric emptying in diabetic gastroparesis is a complex process with multi-components,multi-targets and multi-pathways,and provides a new idea for followup researches.展开更多
Objective:To investigate the anti-diabetic effect of the root extract of Annona muricata(AME)in streptozotocin-nicotinamide-induced type 2 diabetic(T2DM)mice.Methods:After 4 weeks of high-fat diet,ICR mice were given ...Objective:To investigate the anti-diabetic effect of the root extract of Annona muricata(AME)in streptozotocin-nicotinamide-induced type 2 diabetic(T2DM)mice.Methods:After 4 weeks of high-fat diet,ICR mice were given 1 g/kg nicotine and 120 mg/kg streptozotocin(STZ)orally to construct a T2DM model.The T2DM mice were randomly divided into five groups:model group,200 mg/kg metformin group and 50,100,200 mg/kg AME groups.Drugs were oral administered continuously for 4 weeks.Fasting blood glucose and body weight were measured weekly.Oral glucose tolerance test(OGTT)and detection of serum glycated hemoglobin(HbA1c)level were performed one week before the end of the experiment.At the end of drug administration,serum total cholesterol(TG),triglycerides(TC),low-density lipoprotein levels(LDL-C)and insulin levels were tested by lipid detection kits;homeostasis model assessment-estimated insulin resistance(HOMA-IR)and HOMA-βindexes were calculated.Liver and kidney tissues were weighed to calculate organ indices and pathological tests were performed.Western blot was performed in the liver to detect adenosine monophosphate-activated protein kinase(AMPK),acetyl coenzyme A carboxylase(ACC),glucose-6-phosphate carboxylase(G6Pase),and phosphoenolpyruvate carboxykinase(PCK1)protein expression.Results:with 200 mg/kg AME significantly reduced fasting blood glucose,HbA1c,TG and LDL-C levels,protected liver and kindey in diabetic mice,decreased the area under the OGTT curve,inhibited ACC and G6Pase protein expressions,and activated AMPK protein expression.Conclusion:AME showed good therapeutic activity against T2DM,and the mechanism may be related to the activation of AMPK and inhibition of ACC and G6Pase proteins.展开更多
目的观察当归多糖对阿尔茨海默病(AD)模型大鼠学习记忆、海马β-淀粉样蛋白前体(APP)、β-淀粉样蛋白(Aβ)1-42及血清乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响,探讨其防治AD...目的观察当归多糖对阿尔茨海默病(AD)模型大鼠学习记忆、海马β-淀粉样蛋白前体(APP)、β-淀粉样蛋白(Aβ)1-42及血清乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响,探讨其防治AD的作用机制。方法 70只SPF级Wistar大鼠经水迷宫学习记忆能力筛选合格后,随机选取10只大鼠(雌雄各半)为假手术组,其余大鼠以脑立体定位注射Aβ25-35复制AD大鼠模型,以水迷宫学习记忆能力筛选造模成功的50只大鼠随机分为模型组、阳性药组和当归多糖低、中、高剂量组,每组10只。模型组和假手术组大鼠给予生理盐水灌胃,各给药组大鼠给予相应药液灌胃,每日给药体积均为2 m L/100 g,连续28 d。给药25~28 d Morris水迷宫测试大鼠学习记忆能力,然后取材检测血清Ach、ChAT、AChE、SOD、MDA及海马APP、Aβ1-42。结果与假手术组比较,模型组大鼠定位航行实验逃避潜伏期明显延长,目标象限滞留时间缩短,空间探索实验首次到达原逃生平台位置潜伏时间延长,穿越原平台位置及目标象限滞留的时间缩短,血清Ach含量与ChAT、SOD活性明显降低,AChE活性及MDA水平明显升高,海马APP、Aβ1-42含量升高,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,各给药组大鼠逃避潜伏期均不同程度缩短,目标象限滞留时间延长,首次到达原逃生平台位置潜伏时间缩短,跨原平台次数增加,血清Ach含量和ChAT、SOD活性升高,AChE活性及MDA水平明降低,海马APP、Aβ1-42含量降低,差异均有统计学意义(P<0.05,P<0.01)。结论当归多糖可能通过改善胆碱能神经递质、提高抗自由基氧化能力及促进Aβ的代谢,改善AD模型大鼠学习记忆能力,对AD有一定的防治作用。展开更多
目的观察黄芩苷对胃癌BGC-823、MGC-803细胞迁移的影响,探讨其可能的作用机制。方法划痕实验和Transwell小室观察Toll样受体(TLR)激活后以及黄芩苷干预TLR激活后胃癌BGC-823、MGC-803细胞迁移能力;RT-q PCR和Western blot检测胃癌BGC-82...目的观察黄芩苷对胃癌BGC-823、MGC-803细胞迁移的影响,探讨其可能的作用机制。方法划痕实验和Transwell小室观察Toll样受体(TLR)激活后以及黄芩苷干预TLR激活后胃癌BGC-823、MGC-803细胞迁移能力;RT-q PCR和Western blot检测胃癌BGC-823、MGC-803细胞的TLR4、激活蛋白-1(AP-1)、血管内皮生长因子(VEGF)m RNA和蛋白表达。结果脂多糖(LPS)可促进胃癌BGC-823、MGC-803细胞迁移,黄芩苷可抑制LPS干预后胃癌BGC-823、MGC-803细胞迁移;LPS可上调TLR4、AP-1、VEGF m RNA和蛋白表达,黄芩苷可下调LPS干预后胃癌BGC-823、MGC-803细胞的TLR4、AP-1、VEGF m RNA和蛋白表达。结论黄芩苷可阻断TLR4-AP-1-VEGF的激活,从而抑制胃癌BGC-823、MGC-803细胞的迁移。展开更多
基金National Natural Science Foundation of China(81860749)。
文摘Objective:To explore the potential active components,therapeutic targets and critical path of Alpinia officinarum and Pogostemonis Herba in the treatment of diabetic gastroparesis(DGP)by using network pharmacology.Methods:The main chemical components and corresponding targets genes of A.officinarum-Pogostemonis Herba were screened through TCMSP database retrieval[oral bioavailability(OB)≥30%and drug like(DL)≥0.18].Tgenes of diabetic gastroparesis were screened by the Human Gene Database(GeneCards),and Venny 2.1 software was used to obtained common targets for the active ingredients of A.officinarum-Pogostemonis Herba and DGP.Then,the protein-protein interaction(PPI)network of the common targets was constructed by STRING database and analyzed to performed the core targets.GO function and KEGG pathway enrichment analysis of the common target genes were obtained by using ClusterProfiler R package.Finally,the network diagram of"active ingredient-pathway-target"was used to establish by Cytoscape 3.8 software.Results:Totally 23 ingredients of A.officinarum-Pogostemonis Herba,97 active ingredients targets and 533 DGP related targets,including 46 common targets were selected.The common targets were mainly enriched in the cell constituents such as the nuclear chromatin and mitochondria outer membrane,involved in the biological processes as oxidative stress,apoptosis signal regulation,and molecular functions as enzyme binding,protein phosphatase binding,and cytokine activity.They were also concentrated in the signal pathways such as PI3K/Akt,HIF-1 and MAPK.The network of“active ingredients-targets-pathways”indicated the active components such as quercetin,kaempferol and galangin in A.officinarum-Pogostemonis Herba played an anti-delayed gastric emptying in diabetic gastroparesis by acting on PTGS2,NOS2,BCL2,IL6,VEGFA and other targets to jointly regulate PI3K-Akt,HIF-1 and MAPK pathways.Conclusion:This study initially reveals that the combined treatment of A.officinarum-Pogostemonis Herba for delayed gastric emptying in diabetic gastroparesis is a complex process with multi-components,multi-targets and multi-pathways,and provides a new idea for followup researches.
基金National Natural Science Foundation of China(No.81460591)Hainan Medical University Training Fund(HY2018-09)。
文摘Objective:To investigate the anti-diabetic effect of the root extract of Annona muricata(AME)in streptozotocin-nicotinamide-induced type 2 diabetic(T2DM)mice.Methods:After 4 weeks of high-fat diet,ICR mice were given 1 g/kg nicotine and 120 mg/kg streptozotocin(STZ)orally to construct a T2DM model.The T2DM mice were randomly divided into five groups:model group,200 mg/kg metformin group and 50,100,200 mg/kg AME groups.Drugs were oral administered continuously for 4 weeks.Fasting blood glucose and body weight were measured weekly.Oral glucose tolerance test(OGTT)and detection of serum glycated hemoglobin(HbA1c)level were performed one week before the end of the experiment.At the end of drug administration,serum total cholesterol(TG),triglycerides(TC),low-density lipoprotein levels(LDL-C)and insulin levels were tested by lipid detection kits;homeostasis model assessment-estimated insulin resistance(HOMA-IR)and HOMA-βindexes were calculated.Liver and kidney tissues were weighed to calculate organ indices and pathological tests were performed.Western blot was performed in the liver to detect adenosine monophosphate-activated protein kinase(AMPK),acetyl coenzyme A carboxylase(ACC),glucose-6-phosphate carboxylase(G6Pase),and phosphoenolpyruvate carboxykinase(PCK1)protein expression.Results:with 200 mg/kg AME significantly reduced fasting blood glucose,HbA1c,TG and LDL-C levels,protected liver and kindey in diabetic mice,decreased the area under the OGTT curve,inhibited ACC and G6Pase protein expressions,and activated AMPK protein expression.Conclusion:AME showed good therapeutic activity against T2DM,and the mechanism may be related to the activation of AMPK and inhibition of ACC and G6Pase proteins.
文摘目的观察当归多糖对阿尔茨海默病(AD)模型大鼠学习记忆、海马β-淀粉样蛋白前体(APP)、β-淀粉样蛋白(Aβ)1-42及血清乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AChE)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响,探讨其防治AD的作用机制。方法 70只SPF级Wistar大鼠经水迷宫学习记忆能力筛选合格后,随机选取10只大鼠(雌雄各半)为假手术组,其余大鼠以脑立体定位注射Aβ25-35复制AD大鼠模型,以水迷宫学习记忆能力筛选造模成功的50只大鼠随机分为模型组、阳性药组和当归多糖低、中、高剂量组,每组10只。模型组和假手术组大鼠给予生理盐水灌胃,各给药组大鼠给予相应药液灌胃,每日给药体积均为2 m L/100 g,连续28 d。给药25~28 d Morris水迷宫测试大鼠学习记忆能力,然后取材检测血清Ach、ChAT、AChE、SOD、MDA及海马APP、Aβ1-42。结果与假手术组比较,模型组大鼠定位航行实验逃避潜伏期明显延长,目标象限滞留时间缩短,空间探索实验首次到达原逃生平台位置潜伏时间延长,穿越原平台位置及目标象限滞留的时间缩短,血清Ach含量与ChAT、SOD活性明显降低,AChE活性及MDA水平明显升高,海马APP、Aβ1-42含量升高,差异均有统计学意义(P<0.05,P<0.01);与模型组比较,各给药组大鼠逃避潜伏期均不同程度缩短,目标象限滞留时间延长,首次到达原逃生平台位置潜伏时间缩短,跨原平台次数增加,血清Ach含量和ChAT、SOD活性升高,AChE活性及MDA水平明降低,海马APP、Aβ1-42含量降低,差异均有统计学意义(P<0.05,P<0.01)。结论当归多糖可能通过改善胆碱能神经递质、提高抗自由基氧化能力及促进Aβ的代谢,改善AD模型大鼠学习记忆能力,对AD有一定的防治作用。
文摘目的观察黄芩苷对胃癌BGC-823、MGC-803细胞迁移的影响,探讨其可能的作用机制。方法划痕实验和Transwell小室观察Toll样受体(TLR)激活后以及黄芩苷干预TLR激活后胃癌BGC-823、MGC-803细胞迁移能力;RT-q PCR和Western blot检测胃癌BGC-823、MGC-803细胞的TLR4、激活蛋白-1(AP-1)、血管内皮生长因子(VEGF)m RNA和蛋白表达。结果脂多糖(LPS)可促进胃癌BGC-823、MGC-803细胞迁移,黄芩苷可抑制LPS干预后胃癌BGC-823、MGC-803细胞迁移;LPS可上调TLR4、AP-1、VEGF m RNA和蛋白表达,黄芩苷可下调LPS干预后胃癌BGC-823、MGC-803细胞的TLR4、AP-1、VEGF m RNA和蛋白表达。结论黄芩苷可阻断TLR4-AP-1-VEGF的激活,从而抑制胃癌BGC-823、MGC-803细胞的迁移。
