基于系统药理学的续断治疗骨质疏松作用机制研究
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摘要
目的利用系统药理学的方法探讨续断治疗骨质疏松的可能作用机制。方法使用中药系统药理学数据库(TCMSP)获得续断的药物成分,筛选活性成分,预测靶蛋白。在TTD和CTD数据库查询骨质疏松对应靶蛋白,构建药物-靶蛋白-疾病相互作用网络。借助DAVID数据库对核心靶蛋白作用通路进行分析。利用String数据库构建主要信号通路的蛋白质相互作用网络。结果获得7个续断活性成分及其63个靶蛋白,筛选到骨质疏松疾病靶蛋白118个,得到续断与骨质疏松交叉作用蛋白118个,进而富集到与细胞增殖分化及免疫功能等相关的24条信号通路,其中PI3K-AKT信号通路包含有最多数量的相关基因。String数据库分析表明AKT1、MAPK1、MAPK3在信号通路中出现的频率较高。结论续断可能主要通过AKT1、MAPK1、MAPK3影响PI3K-AKT信号通路治疗骨质疏松。
Objective To explore the possible mechanism of Dipsaci Radix in the treatment of osteoporosis based on systems pharmacology method. Methods The drug components of Dipsaci Radix were obtained from TCMSP database to screen active ingredients and predict target protein. The target protein of osteoporosis was searched in the TTD and CTD database in order to build Drug-Target protein-Disease interaction Network. Then, the analysis on the role of core target protein pathways were performed by DAVID tool. The protein interaction network of primary signal pathways was built in String database. Results Seven active ingredients of Dipsaci Radix and their 63 target proteins were obtained, 118 targets of osteoporosis were selected, and 118 cross-acting proteins between Dipsaci Radix and osteoporosis were obtained. Then 24 signaling pathways related to cell proliferation and differentiation and immune function were enriched, wherein PI3 K-AKT signaling pathway contained the largest number of related genes. String database analysis showed that AKT1, MAPK1, and MAPK3 protein appeared frequently in signal pathways. Conclusion Dipsaci Radix may affect the PI3 K-AKT signaling pathway mainly through AKT1, MAPK1, and MAPK3 for the treatment of osteoporosis. This study provides a new idea for the further mechanism study on the treatment of osteoporosis of Dipsaci Radix.
Objective To explore the possible mechanism of Dipsaci Radix in the treatment of osteoporosis based on systems pharmacology method. Methods The drug components of Dipsaci Radix were obtained from TCMSP database to screen active ingredients and predict target protein. The target protein of osteoporosis was searched in the TTD and CTD database in order to build Drug-Target protein-Disease interaction Network. Then, the analysis on the role of core target protein pathways were performed by DAVID tool. The protein interaction network of primary signal pathways was built in String database. Results Seven active ingredients of Dipsaci Radix and their 63 target proteins were obtained, 118 targets of osteoporosis were selected, and 118 cross-acting proteins between Dipsaci Radix and osteoporosis were obtained. Then 24 signaling pathways related to cell proliferation and differentiation and immune function were enriched, wherein PI3 K-AKT signaling pathway contained the largest number of related genes. String database analysis showed that AKT1, MAPK1, and MAPK3 protein appeared frequently in signal pathways. Conclusion Dipsaci Radix may affect the PI3 K-AKT signaling pathway mainly through AKT1, MAPK1, and MAPK3 for the treatment of osteoporosis. This study provides a new idea for the further mechanism study on the treatment of osteoporosis of Dipsaci Radix.
引文
[1]范超领,葛继荣.补肾方药影响骨质疏松症相关信号转导通路的研究进展[J].中国骨质疏松杂志,2014,20(4):446-451.
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[12]武密山,赵素芝,任立中,等.川续断皂苷VI诱导大鼠骨髓间充质干细胞向成骨细胞方向分化的研究[J].中国药理学通报,2012,28(2):222-226.
[13]李家,林晓晟,王雅冰,等.续断皂苷VI对小鼠骨髓基质干细胞成骨分化的影响[J].口腔颌面修复学杂志,2017,18(1):28-32.
[14]陈亚辉,龚忠勤,崔燎,等.PI3K/Akt信号通路在骨质疏松病理过程中的作用[J].中国骨质疏松杂志,2015,21(3):356-360.
[15]张波,耿彬,谭小义,等.MAPK信号通路与骨质疏松关系的研究进展[J].中国矫形外科杂志,2014,22(23):2161-2164.
[16]王小娜,李正,王4,等.TGF-β1在雷奈酸锶促进大鼠骨髓间充质干细胞向成骨细胞分化中的作用[J].中国病理生理杂志,2011,27(12):2357-2361.
[17]罗明,黄宏兴,黄红,等.Hedgehog信号通路与骨质疏松症[J].中国骨伤,2014,27(2):169-172.
[18]Ke K,Li Q,Yang X F,et al.Asperosaponin VI promotes bone marrow stromal cell osteogenic differentiation through the PI3K/AKT signaling pathway in an osteoporosis model[J].Sci Rep,2016,doi:10.1038/srep35233.
[19]Adapala N S,Barbe M F,Tsygankov A Y,et al.Loss of Cbl-PI3K interaction enhances osteoclast survival due to p21-Ras mediated PI3K activation independent of Cbl-b[J].Cell Biochem,2014,115(7):1277-1289.
[20]Kim H K,Kim M G,Leem K H.Osteogenic activity of collagen peptide via ERK/MAPK pathway mediated boosting of collagen synthesis and its therapeutic efficacy in osteoporotic bone by back-scattered electron imaging and microarchitecture analysis[J].Molecules(BaselSwitzerland),2013,18(12):15474-15489.
[2]宋芳婷,李冬梅.补肾中药抗骨质疏松机理研究进展[J].黑龙江中医药,2013,42(1):55-56.
[3]Zhao X L,Feng Y X,Peng Y.Prevention and treatment of osteoporosis with Chinese herbal medicines[J].Chin Herb Med,2012,4(4):265-270.
[4]牛银波,潘亚磊,李晨睿,等.续断防治骨质疏松的研究进展[J].中国药理学通报,2013,29(7):892-894.
[5]王永华,杨凌.基于系统药理学的现代中药研究体系[J].世界中医药,2013,8(7):801-808.
[6]Xue R,Fang Z,Zhang M,et al.TCMID:Traditional Chinese medicine integrative database for herb molecular mechanism analysis[J].Nucleic Acids Res,2013,doi:10.1093/nar/gks1100.
[7]Zheng C,Wang J,Liu J,et al.System-level multi-target drug discovery from natural products with applications to cardiovascular diseases[J].Mol Divers,2014,18(3):621-635.
[8]李静,高丽,高耀,等.基于网络药理学的款冬花止咳化痰活性成分靶点探究[J].中草药,2018,49(1):179-187.
[9]Zhu F,Shi Z,Qin C,et al.Therapeutic target database updata 2012:A resource for facilitating target-oriented drug discovery[J].Nucleic Acids Res,2012,doi:10.1093/nar/gkr797.
[10]Martin A,Ochagavia M E,Rabasa L C,et al.Biso Genet:A new tool for gene network building,visualization and analysis[J].BMC Bioinformatics,2010,doi:1186/1471-2105-11-91.
[11]张潇,高耀,向欢,等.基于网络药理学的交泰丸治疗抑郁症作用机制研究[J].中草药,2017,48(8):1584-1590.
[12]武密山,赵素芝,任立中,等.川续断皂苷VI诱导大鼠骨髓间充质干细胞向成骨细胞方向分化的研究[J].中国药理学通报,2012,28(2):222-226.
[13]李家,林晓晟,王雅冰,等.续断皂苷VI对小鼠骨髓基质干细胞成骨分化的影响[J].口腔颌面修复学杂志,2017,18(1):28-32.
[14]陈亚辉,龚忠勤,崔燎,等.PI3K/Akt信号通路在骨质疏松病理过程中的作用[J].中国骨质疏松杂志,2015,21(3):356-360.
[15]张波,耿彬,谭小义,等.MAPK信号通路与骨质疏松关系的研究进展[J].中国矫形外科杂志,2014,22(23):2161-2164.
[16]王小娜,李正,王4,等.TGF-β1在雷奈酸锶促进大鼠骨髓间充质干细胞向成骨细胞分化中的作用[J].中国病理生理杂志,2011,27(12):2357-2361.
[17]罗明,黄宏兴,黄红,等.Hedgehog信号通路与骨质疏松症[J].中国骨伤,2014,27(2):169-172.
[18]Ke K,Li Q,Yang X F,et al.Asperosaponin VI promotes bone marrow stromal cell osteogenic differentiation through the PI3K/AKT signaling pathway in an osteoporosis model[J].Sci Rep,2016,doi:10.1038/srep35233.
[19]Adapala N S,Barbe M F,Tsygankov A Y,et al.Loss of Cbl-PI3K interaction enhances osteoclast survival due to p21-Ras mediated PI3K activation independent of Cbl-b[J].Cell Biochem,2014,115(7):1277-1289.
[20]Kim H K,Kim M G,Leem K H.Osteogenic activity of collagen peptide via ERK/MAPK pathway mediated boosting of collagen synthesis and its therapeutic efficacy in osteoporotic bone by back-scattered electron imaging and microarchitecture analysis[J].Molecules(BaselSwitzerland),2013,18(12):15474-15489.