Network-based drug repurposing for potential stroke therapy.
Network-based drug repurposing for potential stroke therapy.
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基于网络的药物重新利用潜在的中风疗法。
DOI：
10.1016/j.csbj.2023.04.018
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发表时间：
2023
影响因子：
6
通讯作者：
Gu, Yong
中科院分区：
文献类型：
--
作者：
Wu, Qihui;Chen, Cuilan;Liu, Weihua;Zhou, Yuying;Weng, Guohu;Gu, Yong
中风是全球死亡和残疾的主要原因，在发展中国家的发病率越来越高。然而，目前针对这种疾病的药物治疗很少。药物再利用作为一种有效的药物发现策略出现，具有成本低、时间短的优点，能够从现有药物中发现新的适应症。在这项研究中，我们的目的是通过计算重新利用Drugbank数据库中已批准的药物来识别潜在的中风候选药物。我们首先开发了一个已批准药物的药物靶点网络，采用基于网络的方法重新使用这些药物，共确定了185种治疗中风的候选药物。为了验证我们基于网络的方法的预测准确性，我们接下来系统地搜索了以前的文献，发现185种候选药物中有68种（36.8%）对中风有治疗作用。我们进一步选择了几种具有神经保护作用的潜在候选药物，以测试其抗中风活性。桂利嗪、奥芬那君、苯乙肼、酮替芬、双氯芬酸和奥美拉唑等6种药物对氧糖剥夺/复氧（OGD/R）诱导的BV 2细胞有较好的抑制作用。最后，我们通过蛋白质印迹和Olink炎症面板展示了桂利嗪和苯乙肼的抗中风作用机制。实验结果表明，二者均能通过抑制IL-6和考克斯-2的表达而发挥抗OGD/R诱导的BV 2细胞中风作用。总而言之，本研究为计算机模拟识别治疗中风的候选药物提供了有效的基于网络的方法。
Stroke is the leading cause of death and disability worldwide, with a growing number of incidences in developing countries. However, there are currently few medical therapies for this disease. Emerged as an effective drug discovery strategy, drug repurposing which owns lower cost and shorter time, is able to identify new indications from existing drugs. In this study, we aimed at identifying potential drug candidates for stroke via computationally repurposing approved drugs from Drugbank database. We first developed a drug-target network of approved drugs, employed network-based approach to repurpose these drugs, and altogether identified 185 drug candidates for stroke. To validate the prediction accuracy of our network-based approach, we next systematically searched for previous literature, and found 68 out of 185 drug candidates (36.8 %) exerted therapeutic effects on stroke. We further selected several potential drug candidates with confirmed neuroprotective effects for testing their anti-stroke activity. Six drugs, including cinnarizine, orphenadrine, phenelzine, ketotifen, diclofenac and omeprazole, have exhibited good activity on oxygen-glucose deprivation/reoxygenation (OGD/R) induced BV2 cells. Finally, we showcased the anti-stroke mechanism of actions of cinnarizine and phenelzine via western blot and Olink inflammation panel. Experimental results revealed that they both played anti-stroke effects in the OGD/R induced BV2 cells via inhibiting the expressions of IL-6 and COX-2. In summary, this study provides efficient network-based methodologies for in silico identification of drug candidates toward stroke.
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DOI：
10.1161/atvbaha.117.309868
发表时间：
2017-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Adili R;Tourdot BE;Mast K;Yeung J;Freedman JC;Green A;Luci DK;Jadhav A;Simeonov A;Maloney DJ;Holman TR;Holinstat M
通讯作者：
Holinstat M
影响因子：
16.6
作者：
Cheng F;Desai RJ;Handy DE;Wang R;Schneeweiss S;Barabási AL;Loscalzo J
通讯作者：
Loscalzo J
影响因子：
158.5
作者：
Feigin, Valery L.;Nguyen, Grant;Roth, Gregory A.
通讯作者：
Roth, Gregory A.
影响因子：
8.3
作者：
HOFF, JT;NISHIMURA, M;NEWFIELD, P
通讯作者：
NEWFIELD, P
影响因子：
6
作者：
Wu, Qihui;Su, Shijie;Cai, Chuipu;Xu, Lina;Fan, Xiude;Ke, Hanzhong;Dai, Zhao;Fang, Shuhuan;Zhuo, Yue;Wang, Qi;Pan, Huafeng;Gu, Yong;Fang, Jiansong
通讯作者：
Fang, Jiansong