Target Identification of Active Constituents of Shen Qi Wan to Treat Kidney Yang Deficiency Using Computational Target Fishing and Network Pharmacology
Target Identification of Active Constituents of Shen Qi Wan to Treat Kidney Yang Deficiency Using Computational Target Fishing and Network Pharmacology
复制标题
利用计算标靶钓鱼和网络药理学对参芪丸治疗肾阳虚的活性成分进行靶标鉴定
DOI：
10.3389/fphar.2019.00650
复制
发表时间：
2019-06
影响因子：
5.6
通讯作者：
Li Chang Yu
中科院分区：
文献类型：
--
作者：
Zhang Jie Ying;Hong Chun Lan;Chen Hong Shu;Zhou Xiao Jie;Zhang Yu Jia;Efferth Thomas;Yang Yuan Xiao;Li Chang Yu
背景：肾阳虚证(KYDS)是中老年患者最常见的中医证候之一。参七丸数百年来一直被有效地用于治疗与KYDS相关的各种疾病。然而，由于SQW的组成复杂，其作用机制尚不清楚。目的：探讨四君子汤治疗KYDS的作用机制，并确定其分子靶点。方法：利用PharmMapper软件对参附饮片中有效成分的潜在靶点进行预测。使用分子注释系统(MAS3.0)进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径富集化分析。利用Cytoscape构建了这些潜在靶点的蛋白质-蛋白质相互作用(PPI)网络和“组分-靶点-通路”相互作用网络。我们还建立了腺嘌呤诱导的KYDS大鼠模型，观察了参附颗粒对KYDS的治疗作用。测定体重、直肠温度、握力、饮水量、尿量、血尿素氮(BUN)、血肌酐(Scr)、促肾上腺皮质激素(ACTH)、皮质醇(CORT)、尿总蛋白(U-TP)和17-羟基皮质类固醇(17-uchS)。采用定量聚合酶链式反应(QPCR)检测候选基因的mRNA表达水平。结果：四逆汤治疗后大鼠体重、直肠温度、握力、饮水量、尿量、BUN、Scr、ACTH、CORT、U-TP、17-uchS的变化均纠正至基线值。我们选择了每个组分的前10个靶点，得到了79个潜在的靶点，这些靶点主要集中在蛋白降解、蛋白结合、转移酶活性、T细胞受体信号通路和焦点黏附等方面。SRC、MAPK14、HRAS、HSP90AA1、F2、LCK、CDK2和MMP9被确定为苦参丸治疗KYDS的靶点。参附颗粒显著抑制SRC、HSP90AA1、LCK和CDK2的表达，显著上调MAPK14、MMP9和F2的表达。然而，HRAS水平保持不变。结论：参麦冲剂能纠正KYDS所致大鼠下丘脑-垂体-靶腺轴的紊乱。确定SRC、MAPK14、HRAS、HSP90AA1、F2、LCK、CDK2、MMP9为治疗靶点，为进一步研究四逆汤改善KYDS奠定基础。
Background: Kidney yang deficiency syndrome (KYDS) is one of the most common syndromes treated with traditional Chinese medicine (TCM) among elderly patients. Shen Qi Wan (SQW) has been effectively used in treating various diseases associated with KYDS for hundreds of years. However, due to the complex composition of SQW, the mechanism of action remains unknown. Purpose: To identify the mechanism of the SQW in the treatment of KYDS and determine the molecular targets of SQW. Methods: The potential targets of active ingredients in SQW were predicted using PharmMapper. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the Molecule Annotation System (MAS3.0). The protein–protein interaction (PPI) network of these potential targets and “components-targets-pathways” interaction networks were constructed using Cytoscape. We also established a KYDS rat model induced by adenine to investigate the therapeutic effects of SQW. Body weight, rectal temperature, holding power, water intake, urinary output, blood urea nitrogen (BUN), serum creatinine (Scr), adrenocorticotrophic hormone (ACTH), cortisol (CORT), urine total protein (U-TP), and 17-hydroxy-corticosteroid (17-OHCS) were measured. Additionally, the mRNA expression levels of candidates were detected by qPCR. Results: KYDS-caused changes in body weight, rectal temperature, holding power, water intake, urinary output, BUN, Scr, ACTH, CORT, U-TP, and 17-OHCS were corrected to the baseline values after SQW treatment. We selected the top 10 targets of each component and obtained 79 potential targets, which were mainly enriched in the proteolysis, protein binding, transferase activity, T cell receptor signaling pathway, and focal adhesion. SRC, MAPK14, HRAS, HSP90AA1, F2, LCK, CDK2, and MMP9 were identified as targets of SQW in the treatment of KYDS. The administration of SQW significantly suppressed the expression of SRC, HSP90AA1, LCK, and CDK2 and markedly increased the expression of MAPK14, MMP9, and F2. However, HRAS levels remained unchanged. Conclusion: These findings demonstrated that SQW corrected hypothalamic–pituitary–target gland axis disorder in rats caused by KYDS. SRC, MAPK14, HRAS, HSP90AA1, F2, LCK, CDK2, and MMP9 were determined to the therapeutic target for the further investigation of SQW to ameliorate KYDS.
登录
查看更多内容
DOI：
10.1155/2016/2960372
发表时间：
2016
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Liu H;Zeng L;Yang K;Zhang G
通讯作者：
Zhang G
影响因子：
3.4
作者：
Chang CT;Chang WL;Hsu JC;Shih Y;Chou ST
通讯作者：
Chou ST
影响因子：
2.1
作者：
A. Hasegawa;M. Yoshino;Hiroyoshi Nakamura;I. Ishii;Toshiko Watanabe;M. Kiuchi;T. Ishikawa;S. Ohmori;M. Kitada
通讯作者：
A. Hasegawa;M. Yoshino;Hiroyoshi Nakamura;I. Ishii;Toshiko Watanabe;M. Kiuchi;T. Ishikawa;S. Ohmori;M. Kitada
DOI：
10.1002/9781118788516.sem069
发表时间：
2020-11
期刊：
--
影响因子：
--
作者：
C. Mayr
通讯作者：
C. Mayr
影响因子：
9.6
作者：
M. Roy;P. Carey
通讯作者：
M. Roy;P. Carey