Shuai Yongming, Jiang Zhili, Yuan Qiuwen, Tu Shuqiang, Zeng Fanhui
Nanchang Hongdu Hospital of Traditional Chinese Medicine, 264 Minde Road, Donghu District, Nanchang, Jiangxi 330006, China.
Evid Based Complement Alternat Med. 2020 Sep 7;2020:7049812. doi: 10.1155/2020/7049812. eCollection 2020.
Du Zhong (DZ), or Eucommiae Cortex, a traditional Chinese herbal medicine, has been used to treat osteoporosis. Although it has been reported that DZ can improve bone mass in ovariectomized rats, its pharmacological mechanisms in treating osteoporotic fractures (OPF) remain unclear.
In this study, we used a network pharmacological manner to explore its potential complicated mechanism in treating OPF. We obtained DZ compounds from TCMSP and BATMAN-TCM databases and collected potential targets of these compounds through target fishing based on TCMSP and BATMAN-TCM databases. Next, we collected the OPF targets by using CTD, GeneCards, OMIM, HPO, and GenCLiP 3 databases. And then the overlapping genes between DZ potential targets and OPF targets were used to build up the protein-protein interaction (PPI) network and to analyze their interactions and find out the big hub genes in this network. Subsequently, clusterProfiler package in language was utilized to conduct the enrichment of Gene Ontology biological process and KEGG pathways.
There were totally 93 active compounds and 916 related targets in DZ. After the enrichment analysis, we collected top 25 cellular biological processes and top 25 pathways based on the adjusted value and found that the DZ anti-OPF effect was mainly associated with the regulation of ROS and inflammatory response. Furthermore, 64 hub genes in PPI network, such as MAPK1 (degree = 41), SRC (degree = 39), PIK3R1 (degree = 36), VEGFA (degree = 31), TP53 (degree = 29), EGFR (degree = 29), JUN (degree = 29), AGT (degree = 29), MAPK1, SRC, PIK3R1, VEGFA, and TP53, were considered as potential therapeutic targets, implying the underlying mechanisms of DZ acting on OPF.
We investigated the possible therapeutic mechanisms of DZ from a systemic perspective. These key targets and pathways provided promising directions for the future research to reveal the exact regulating mechanisms of DZ in treating OPF.
杜仲是一种传统的中药材，已被用于治疗骨质疏松症。尽管已有报道称杜仲可提高去卵巢大鼠的骨量，但其治疗骨质疏松性骨折（OPF）的药理机制仍不清楚。
在本研究中，我们采用网络药理学方法探讨其治疗OPF的潜在复杂机制。我们从中药系统药理学数据库（TCMSP）和中药综合数据库（BATMAN-TCM）中获取杜仲化合物，并通过基于TCMSP和BATMAN-TCM数据库的靶点垂钓收集这些化合物的潜在靶点。接下来，我们使用比较毒理基因组学数据库（CTD）、基因卡片数据库（GeneCards）、在线人类孟德尔遗传数据库（OMIM）、人类表型本体数据库（HPO）和基因共表达链接预测器3数据库（GenCLiP 3）收集OPF靶点。然后，利用杜仲潜在靶点与OPF靶点之间的重叠基因构建蛋白质-蛋白质相互作用（PPI）网络，分析它们的相互作用，并找出该网络中的关键枢纽基因。随后，使用R语言中的clusterProfiler软件包进行基因本体生物学过程和京都基因与基因组百科全书（KEGG）通路的富集分析。
杜仲中共有93种活性化合物和916个相关靶点。经过富集分析，我们根据校正后的P值收集了前25个细胞生物学过程和前25条通路，发现杜仲抗OPF的作用主要与活性氧（ROS）的调节和炎症反应有关。此外，PPI网络中的64个枢纽基因，如丝裂原活化蛋白激酶1（MAPK1，度=41）、原癌基因酪氨酸蛋白激酶（SRC，度=39）、磷脂酰肌醇-3激酶调节亚基1（PIK3R1，度=36）、血管内皮生长因子A（VEGFA，度=31）、肿瘤蛋白p53（TP53，度=29）、表皮生长因子受体（EGFR，度=29）、原癌基因蛋白c-Jun（JUN，度=29）、血管紧张素原（AGT，度=29）等，被认为是潜在的治疗靶点，这暗示了杜仲作用于OPF的潜在机制。
我们从系统的角度研究了杜仲可能的治疗机制。这些关键靶点和通路为未来揭示杜仲治疗OPF的确切调控机制的研究提供了有希望的方向。
