基于网络药理学的补肾益髓胶囊治疗多发性硬化机制研究
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摘要
目的应用网络药理学方法分析补肾益髓胶囊主要组成药物的核心组分及治疗多发性硬化可能的分子作用机制,为中药复方研究提供参考。方法检索中药系统药理学数据库和分析平台(TCMSP)收录的补肾益髓胶囊主要组成药物(熟地黄、连翘、大黄、益母草、浙贝母)的化学成分,进行吸收、分布、代谢、排泄(ADME)分析,预测化合物对应的作用靶点。以口服生物利用度≥30%、类药性≥0.18或节点度≥5筛选核心化合物,采用Cytoscape3.2.0构建核心化合物-靶点网络,筛选多发性硬化相关靶点及对应化合物信息。运用STRING数据库构建靶蛋白互作网络,并进行KEGG信号通路富集和GO功能富集。结果筛选出核心组分23种、疾病相关靶点43个、GO生物过程229个、代谢通路54条。结论补肾益髓胶囊治疗多发性硬化主要从调节炎症因子、生长因子,调节细胞免疫,促进髓鞘、轴突再生等方面发挥作用,具有多成分、多靶点的特点,与多条信号通路存在直接或间接关系,是多因素诱导的综合效应。
Objective To explore the core components of Bushen Yisui Capsules and the possible molecular mechanism of treating multiple sclerosis by using network pharmacology; To provide references for research on compound TCM. Methods The main components of Bushen Yisui Capsules(Rehmannize Radix Praeparata,Forsythiae Fructus, Rhei Radix et Rhizoma, Leonuri Herba, and Fritiliariae Thunbergii Bulbus) were retrieved from TCMSP for ADME(absorption, distribution, metabolism, excretion) analysis, and target corresponding compounds were predicted. Core compounds with OB ≥ 30%, DL ≥ 0.18, or nodality ≥ 5 were screened. The core compound-target network was constructed using Cytoscape 3.2.0 to screen multiple sclerosis-related targets and corresponding compound information. STRING database was used to construct a target protein interaction network,and KEGG signaling pathway enrichment and GO function enrichment were conducted. Results Totally 23 core components, 43 disease-related targets, 229 GO biological processes, and 54 metabolic pathways were screened out.Conclusion Bushen Yisui Capsules for the treatment of multiple sclerosis mainly plays a role in regulating inflammatory factor and growth factors, regulating cellular immunity, promoting myelin and axon regeneration, and has multi-component and multi-target characteristics. The mechanism has a direct or indirect relationship with multiple signaling pathways, which is the combined effect of multi-factor induction.
Objective To explore the core components of Bushen Yisui Capsules and the possible molecular mechanism of treating multiple sclerosis by using network pharmacology; To provide references for research on compound TCM. Methods The main components of Bushen Yisui Capsules(Rehmannize Radix Praeparata,Forsythiae Fructus, Rhei Radix et Rhizoma, Leonuri Herba, and Fritiliariae Thunbergii Bulbus) were retrieved from TCMSP for ADME(absorption, distribution, metabolism, excretion) analysis, and target corresponding compounds were predicted. Core compounds with OB ≥ 30%, DL ≥ 0.18, or nodality ≥ 5 were screened. The core compound-target network was constructed using Cytoscape 3.2.0 to screen multiple sclerosis-related targets and corresponding compound information. STRING database was used to construct a target protein interaction network,and KEGG signaling pathway enrichment and GO function enrichment were conducted. Results Totally 23 core components, 43 disease-related targets, 229 GO biological processes, and 54 metabolic pathways were screened out.Conclusion Bushen Yisui Capsules for the treatment of multiple sclerosis mainly plays a role in regulating inflammatory factor and growth factors, regulating cellular immunity, promoting myelin and axon regeneration, and has multi-component and multi-target characteristics. The mechanism has a direct or indirect relationship with multiple signaling pathways, which is the combined effect of multi-factor induction.
引文
[1]樊永平,王平,张星虎,等.二黄方治疗多发性硬化急性发作的临床观察[J].北京中医药大学学报,2006,29(4):273-276,280.
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[4]樊永平,刘秀贞,王蕾,等.二黄方对EAE大鼠外周血NK细胞和细胞因子的影响[J].北京中医药大学学报,2007,30(3):165-168.
[5]樊永平,宋丽君,叶明,等.二黄胶囊对实验性自身免疫性脑脊髓炎大鼠中枢神经系统细胞因子和淋巴细胞亚群免疫组化表达的影响[J].中国实验方剂学杂志,2010,16(5):142-146.
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[8]王蕾,樊永平,龚慕辛,等.二黄胶囊对大鼠变态反应性脑脊髓炎淋巴细胞亚群和NK细胞的影响[J].中药新药与临床药理,2008,19(3):165-169.
[9]赵晖,王蕾,龚慕辛,等.二黄胶囊对实验性自身免疫性脑脊髓炎小鼠细胞免疫的影响[J].首都医科大学学报,2009,30(1):15-19.
[10]郑琦,杨涛,房玲,等.补肾益髓胶囊对实验性自身免疫性脑脊髓炎小鼠大脑内BDNF和Nogo A的影响[J].南京中医药大学学报,2013,29(5):439-444.
[11]STORER P D,XU J,CHAVIS J,et al.Peroxisome proliferatoractivated receptor-gamma agonists inhibit the activation of microglia and astrocytes:implications for multiple sclerosis[J].J Neuroimmunol,2005,161(1/2):113-122.
[12]PAINTLIA A S,PAINTLIA M K,SINGH I,et al.IL-4-induced peroxisome proliferator-activated receptor gamma activation inhibits NF-κB trans activation in central nervous system(CNS)glial cells and protects oligodendrocyte progenitors under neuroinflammatory disease conditions:implication for CNS-demyelinating diseases[J].J Immunol,2006,176(7):4385-4398.
[13]PAINTLIA A S,PAINTLIA M K,SINGH A K,et al.Activation of PPAR-gamma and PTEN cascade participates in lovastatin-mediated accelerated differentiation of oligodendrocyte progenitor cells[J].Glia,2010,58(14):1669-1685.
[14]KLOTZ L,BURGDORF S,DANI I,et al.The nuclear receptor PPARgamma selectively inhibits Th17 differentiation in a Tcell-intrinsic fashion and suppresses CNS autoimmunity[J].J Exp Med,2009,206(10):2079-2089.
[2]樊永平,王平,张星虎,等.二黄方治疗多发性硬化急性发作的机制研究[J].中华中医药杂志,2007,22(1):25-29.
[3]宋丽君,樊永平.补肾为主辨证论治对急性期多发性硬化患者血浆细胞因子的影响[J].中华中医药杂志,2010,25(5):745-748.
[4]樊永平,刘秀贞,王蕾,等.二黄方对EAE大鼠外周血NK细胞和细胞因子的影响[J].北京中医药大学学报,2007,30(3):165-168.
[5]樊永平,宋丽君,叶明,等.二黄胶囊对实验性自身免疫性脑脊髓炎大鼠中枢神经系统细胞因子和淋巴细胞亚群免疫组化表达的影响[J].中国实验方剂学杂志,2010,16(5):142-146.
[6]周莉,樊永平,王蕾,等.二黄方对EAE大鼠细胞因子及Th1/Th2平衡的影响[J].首都医科大学学报,2009,30(1):20-23.
[7]樊永平,周莉,王蕾,等.二黄方对EAE大鼠急性期血浆MCP-1、TNF-α水平的影响[J].北京中医药,2009,28(3):225-227.
[8]王蕾,樊永平,龚慕辛,等.二黄胶囊对大鼠变态反应性脑脊髓炎淋巴细胞亚群和NK细胞的影响[J].中药新药与临床药理,2008,19(3):165-169.
[9]赵晖,王蕾,龚慕辛,等.二黄胶囊对实验性自身免疫性脑脊髓炎小鼠细胞免疫的影响[J].首都医科大学学报,2009,30(1):15-19.
[10]郑琦,杨涛,房玲,等.补肾益髓胶囊对实验性自身免疫性脑脊髓炎小鼠大脑内BDNF和Nogo A的影响[J].南京中医药大学学报,2013,29(5):439-444.
[11]STORER P D,XU J,CHAVIS J,et al.Peroxisome proliferatoractivated receptor-gamma agonists inhibit the activation of microglia and astrocytes:implications for multiple sclerosis[J].J Neuroimmunol,2005,161(1/2):113-122.
[12]PAINTLIA A S,PAINTLIA M K,SINGH I,et al.IL-4-induced peroxisome proliferator-activated receptor gamma activation inhibits NF-κB trans activation in central nervous system(CNS)glial cells and protects oligodendrocyte progenitors under neuroinflammatory disease conditions:implication for CNS-demyelinating diseases[J].J Immunol,2006,176(7):4385-4398.
[13]PAINTLIA A S,PAINTLIA M K,SINGH A K,et al.Activation of PPAR-gamma and PTEN cascade participates in lovastatin-mediated accelerated differentiation of oligodendrocyte progenitor cells[J].Glia,2010,58(14):1669-1685.
[14]KLOTZ L,BURGDORF S,DANI I,et al.The nuclear receptor PPARgamma selectively inhibits Th17 differentiation in a Tcell-intrinsic fashion and suppresses CNS autoimmunity[J].J Exp Med,2009,206(10):2079-2089.