OBJECTIVE:To investigate the protective efficacy of Bushen Culuan decoction补肾促卵方,BCD)on ovarian follicle and follicular granulosa cells in mice with premature ovarian insufficiency(POI)induced by tripterygium wil...OBJECTIVE:To investigate the protective efficacy of Bushen Culuan decoction补肾促卵方,BCD)on ovarian follicle and follicular granulosa cells in mice with premature ovarian insufficiency(POI)induced by tripterygium wilfordii polyglycoside,and to study the potential mechanism underlying the action.METHODS:Eighty female Balb/c mice were randomly divided into 4 groups(n=20 each):blank group,model group,Bushen Culuan decoction intervening group(BCD group)and estradiol valerate intervening group(EV group).In the first 14 model establishing d,mice in model group,BCD group and EV group were under Tripterygium wilfordii polyglycoside(TWP)gavage to establish POI models.In the 14-day therapeutic stage,mice in BCD group were taken BCD 18.35 mg·kg^(-1)·d^(-1),mice in EV group were taken EV solution 0.15 mg·kg^(-1)·d^(-1),while mice in blank group and model group were taken normal saline.When the mice accomplished therapy,whole blood was collected for serum hormone including follicle stimulating hormone(FSH),luteal hormone(LH),estradiol(E2),antimullerian hormone(AMH)levels and vascular endothelial growth factor(VEGF),bone morphogenetic protein-7(BMP-7)measurement.Ovarian tissues were harvested for morphologic observation,follicle counting,ovarian follicular graulosa cell apoptosis test and testing BMP-7 and caspase-3 expressions.RESULTS:The body weights of the mice kept growing stably in the process expect in TWP intervening stage.Compared with model group,BCD group had significantly higher ovarian index,serum E_(2),AMH,VEGF,BMP-7 levels and significantly lower FSH level(P<0.05).Meanwhile the VEGF level in BCD group was higher than in EV group(P<0.05).Compared with model group,the histopathological damage and GCs apoptosis were mitigated;developing follicle counting,BMP-7 expression were up-regulated,and caspase-3 expression was downregulated in BCD groups(P<0.05).CONCLUSION:BCD treatment could attenuate pathological process in POI ovaries,suppress GC apoptosis,probably through promoting BMP-7 expression and following inhibiting caspase-3 activation.展开更多
目的:基于网络药理学和分子对接探讨班氏促卵助孕汤对卵巢储备功能低下的影响。方法:通过中药系统药理学(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中药分子机制分析中药综合数据库(...目的:基于网络药理学和分子对接探讨班氏促卵助孕汤对卵巢储备功能低下的影响。方法:通过中药系统药理学(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中药分子机制分析中药综合数据库(traditional Chinese medicine integrative database for herb molecular mechanism analysis,TCMID)、借助中药分子机理的生物信息学分析工具(bioinformatics analysis tool for molecular mechanism of traditional chinese medicine,BATMAN-TCM)检索班氏促卵助孕汤的活性成分以及作用靶点;通过GeneCards、OMIM数据库获取卵巢储备功能低下的相关靶标。由Cytoscape软件和STRING数据库建立药物-化合物-靶标网络、靶标蛋白互作PPI网络。R语言的cluster Profiler工具包对于核心靶点展开基因本体(gene ontology,GO)功能富集以及基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。最后,对药物活性成分与疾病靶点进行分子对接验证。结果:根据筛选条件得到245个化合物和250个药物相应靶点。PPI核心网络包含80个蛋白,关键蛋白涉及INS、IL6、APP、VEGFA、EGFR、MAPK8等。GO功能富集分析取得1296个条目(P<0.05),其中生物过程(biological process,BP)1094个,细胞组成(cell composition,CC)88个,分子功能(molecular function,MF)114个;KEGG通路富集有63条通路与卵巢储备功能低下相关(P<0.05),涉及cAMP信号通路、HIF-1信号通路、雌激素信号通路、催乳激素信号通路等。分子对接结果表明,班氏排卵促孕汤的主要活性成分槲皮素、山柰酚、β-谷甾醇与核心靶点INS、IL6、APP具有较好的结合活性。结论:班氏促卵助孕汤中的活性化合物可通过多靶点、多通路治疗卵巢储备功能低下。展开更多
基金Supported by Chinese Traditional Medicine“One Belt One Road”International Cooperation Project of China Academy of Chinese Medical Science(No.GH-2017-02-02)。
文摘OBJECTIVE:To investigate the protective efficacy of Bushen Culuan decoction补肾促卵方,BCD)on ovarian follicle and follicular granulosa cells in mice with premature ovarian insufficiency(POI)induced by tripterygium wilfordii polyglycoside,and to study the potential mechanism underlying the action.METHODS:Eighty female Balb/c mice were randomly divided into 4 groups(n=20 each):blank group,model group,Bushen Culuan decoction intervening group(BCD group)and estradiol valerate intervening group(EV group).In the first 14 model establishing d,mice in model group,BCD group and EV group were under Tripterygium wilfordii polyglycoside(TWP)gavage to establish POI models.In the 14-day therapeutic stage,mice in BCD group were taken BCD 18.35 mg·kg^(-1)·d^(-1),mice in EV group were taken EV solution 0.15 mg·kg^(-1)·d^(-1),while mice in blank group and model group were taken normal saline.When the mice accomplished therapy,whole blood was collected for serum hormone including follicle stimulating hormone(FSH),luteal hormone(LH),estradiol(E2),antimullerian hormone(AMH)levels and vascular endothelial growth factor(VEGF),bone morphogenetic protein-7(BMP-7)measurement.Ovarian tissues were harvested for morphologic observation,follicle counting,ovarian follicular graulosa cell apoptosis test and testing BMP-7 and caspase-3 expressions.RESULTS:The body weights of the mice kept growing stably in the process expect in TWP intervening stage.Compared with model group,BCD group had significantly higher ovarian index,serum E_(2),AMH,VEGF,BMP-7 levels and significantly lower FSH level(P<0.05).Meanwhile the VEGF level in BCD group was higher than in EV group(P<0.05).Compared with model group,the histopathological damage and GCs apoptosis were mitigated;developing follicle counting,BMP-7 expression were up-regulated,and caspase-3 expression was downregulated in BCD groups(P<0.05).CONCLUSION:BCD treatment could attenuate pathological process in POI ovaries,suppress GC apoptosis,probably through promoting BMP-7 expression and following inhibiting caspase-3 activation.
文摘目的:基于网络药理学和分子对接探讨班氏促卵助孕汤对卵巢储备功能低下的影响。方法:通过中药系统药理学(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中药分子机制分析中药综合数据库(traditional Chinese medicine integrative database for herb molecular mechanism analysis,TCMID)、借助中药分子机理的生物信息学分析工具(bioinformatics analysis tool for molecular mechanism of traditional chinese medicine,BATMAN-TCM)检索班氏促卵助孕汤的活性成分以及作用靶点;通过GeneCards、OMIM数据库获取卵巢储备功能低下的相关靶标。由Cytoscape软件和STRING数据库建立药物-化合物-靶标网络、靶标蛋白互作PPI网络。R语言的cluster Profiler工具包对于核心靶点展开基因本体(gene ontology,GO)功能富集以及基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。最后,对药物活性成分与疾病靶点进行分子对接验证。结果:根据筛选条件得到245个化合物和250个药物相应靶点。PPI核心网络包含80个蛋白,关键蛋白涉及INS、IL6、APP、VEGFA、EGFR、MAPK8等。GO功能富集分析取得1296个条目(P<0.05),其中生物过程(biological process,BP)1094个,细胞组成(cell composition,CC)88个,分子功能(molecular function,MF)114个;KEGG通路富集有63条通路与卵巢储备功能低下相关(P<0.05),涉及cAMP信号通路、HIF-1信号通路、雌激素信号通路、催乳激素信号通路等。分子对接结果表明,班氏排卵促孕汤的主要活性成分槲皮素、山柰酚、β-谷甾醇与核心靶点INS、IL6、APP具有较好的结合活性。结论:班氏促卵助孕汤中的活性化合物可通过多靶点、多通路治疗卵巢储备功能低下。
