五子衍宗丸网络药理机制初探
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摘要
目的:分析鉴定大鼠口服五子衍宗丸后的血中移行成分,并初步探讨其治疗少弱精子症的网络药理机制。方法:建立UPLC-ESI-LTQ-Orbitrap方法,分析五子衍宗丸的体内成分,鉴定其血中移行成分。随后利用Stitch、DrugBank、OMIM数据库分别获得药物入血成分靶标及与少弱精子症相关的靶标信息。采用String数据库和Cytoscape软件构建五子衍宗丸入血成分-入血成分靶标-少弱精子症靶标网络,再根据网络拓扑结构特征值筛选核心靶标并明确其对应的入血成分并通过Systems Dock Web Site对预测结果进行分子对接验证。最后借助DAVID数据库对核心靶标进行生物学功能和KEGG通路富集分析。结果:鉴定了五子衍宗丸大鼠血中移行成分42个,网络药理分析共筛选到五子衍宗丸入血成分20个,核心靶标78个。其治疗少弱精子症可能主要涉及信号转导、分子功能、催化活性、内环境稳态、生物合成及代谢等生物学过程和神经活性配体-受体相互作用、钙信号、甾体激素生物合成、甘氨酸、丝氨酸及苏氨酸代谢等信号通路。结论:本研究初步阐明了五子衍宗丸的潜在药效物质基础,探讨了五子衍宗丸治疗少弱精子症的作用机制,为更进一步深入研究其药效物质及其药理机制提供了有益参考。
Objective:To analyse and identify constituents absorbed into blood after oral administration of Wuzi-Yanzong-Wan(WZYZW),and to explore the network pharmacological mechanism of WZYZW in treating oligoasthenospermia.Methods:An UPLC-ESI-LTQ-Orbitrap method was established for detecting the components in dosed serum after oral administration of WZYZW.The prototype compounds and metabolites in WZYZW were discovered.Based on the Stitch,DrugBank and OMIM database,the targets of oligoasthenospermia and constituents absorbed into blood were obtained respectively.The network of WZYZW hematopoietic component-hematopoietic componnet target-oligoasthenospermia target was constructed using the String database and Cytoscape software.Only the topological features higher than the corresponding median values were identified as the major putative targets,and matching corresponding component respectively.And the predicted results were verified by molecular docking Systems Dock Web Site.The GO and KEGG pathways involved in the major putative targets were performed using DAVID Database.Results:42 compounds were identified in the rat serum after oral administration of WZYZW.The network pharmacology analysis indicated that 20 constituents absorbed into blood and 78 major putative targets were obtained.The major putative targets of WZYZW were significantly associated with biological processes mainly involved in signal transduction,molecular function,catalytic activity,homeostatic process,biosynthetic and metabolic processes,as well as neuroactive ligand-receptor interaction,calcium signaling pathway,steroid hormone biosynthesis,glycine,serine and threonine metabolism and other signaling pathways.Conclusion:The study preliminarily elucidates the potential pharmacodynamic material basis of WZYZW,explores the mechanism of WZYZW acting on oligoasthenospermia and provides a helpful reference for further study of the pharmacodynamic material basis and pharmacological mechanism of WZYZW.
Objective:To analyse and identify constituents absorbed into blood after oral administration of Wuzi-Yanzong-Wan(WZYZW),and to explore the network pharmacological mechanism of WZYZW in treating oligoasthenospermia.Methods:An UPLC-ESI-LTQ-Orbitrap method was established for detecting the components in dosed serum after oral administration of WZYZW.The prototype compounds and metabolites in WZYZW were discovered.Based on the Stitch,DrugBank and OMIM database,the targets of oligoasthenospermia and constituents absorbed into blood were obtained respectively.The network of WZYZW hematopoietic component-hematopoietic componnet target-oligoasthenospermia target was constructed using the String database and Cytoscape software.Only the topological features higher than the corresponding median values were identified as the major putative targets,and matching corresponding component respectively.And the predicted results were verified by molecular docking Systems Dock Web Site.The GO and KEGG pathways involved in the major putative targets were performed using DAVID Database.Results:42 compounds were identified in the rat serum after oral administration of WZYZW.The network pharmacology analysis indicated that 20 constituents absorbed into blood and 78 major putative targets were obtained.The major putative targets of WZYZW were significantly associated with biological processes mainly involved in signal transduction,molecular function,catalytic activity,homeostatic process,biosynthetic and metabolic processes,as well as neuroactive ligand-receptor interaction,calcium signaling pathway,steroid hormone biosynthesis,glycine,serine and threonine metabolism and other signaling pathways.Conclusion:The study preliminarily elucidates the potential pharmacodynamic material basis of WZYZW,explores the mechanism of WZYZW acting on oligoasthenospermia and provides a helpful reference for further study of the pharmacodynamic material basis and pharmacological mechanism of WZYZW.
引文
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[5]王秋萍,王桐生,龙子江,等.五子衍宗丸对少弱精症模型大鼠精子质量及睾丸组织的影响[J].中成药,2011,33(10):1796-1797.
[6]王学美,谢竹藩,刘庚信,等.五子衍宗液对雄性大鼠下丘脑单胺类递质、性激素和生育能力的影响[J].中国中西医结合杂志,1993,13(6):349-351.
[2]张彦琼,李梢.网络药理学与中医药现代研究的若干进展[J].中国药理学与毒理学杂志,2015,29(6):883-892.
[3]宋来新,张长城,袁丁,等.五子衍宗丸对生殖系统影响的研究进展[J].中成药,2016,38(7):1579-1582.
[4]曾克武,万彦军,廖理曦,等.加味五子衍宗丸神经保护作用靶点群的鉴定与功能分析[J].中国中药杂志,2017,42(19):3656-3660.
[5]王秋萍,王桐生,龙子江,等.五子衍宗丸对少弱精症模型大鼠精子质量及睾丸组织的影响[J].中成药,2011,33(10):1796-1797.
[6]王学美,谢竹藩,刘庚信,等.五子衍宗液对雄性大鼠下丘脑单胺类递质、性激素和生育能力的影响[J].中国中西医结合杂志,1993,13(6):349-351.