Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion

Objective: To investigate the effect of Zhilong Huoxue Tongyu capsule (ZLH) in the treatment of cerebral ischemia–reperfusion injury and determine the underlying molecular network mechanism.Methods: The treatment effect of Zhilong Huoxue Tongyu capsule (ZLH) was evaluated for cerebral ischemia–reper...

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Main Authors: Na Li, Jie Sun, Ji-Lin Chen, Xue Bai, Ting-Hua Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.912392/full
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author Na Li
Jie Sun
Ji-Lin Chen
Xue Bai
Ting-Hua Wang
Ting-Hua Wang
author_facet Na Li
Jie Sun
Ji-Lin Chen
Xue Bai
Ting-Hua Wang
Ting-Hua Wang
author_sort Na Li
collection DOAJ
description Objective: To investigate the effect of Zhilong Huoxue Tongyu capsule (ZLH) in the treatment of cerebral ischemia–reperfusion injury and determine the underlying molecular network mechanism.Methods: The treatment effect of Zhilong Huoxue Tongyu capsule (ZLH) was evaluated for cerebral ischemia–reperfusion injury in middle cerebral artery occlusion (MACO) rat, and the underlying molecular network mechanism was explored by using molecular network analysis based on network pharmacology, bioinformatics including protein–protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), as well as molecular docking.Results: The neurological function of rats in the ZLH group was significantly improved compared to those in the NS group (p = 0.000), confirming the positive effect of ZLH for the treatment of brain ischemia. There were 126 intersecting genes screened in ischemia–reperfusion cerebrum that are associated with several important biological processes, such as lipopolysaccharide, and the most important cell component, such as raft, as well as the most important molecular function pointed as cytokine receptor binding. The most important KEGG signaling pathway was the AGE-RAGE signaling pathway in diabetic complications. Moreover, according to the STRING interaction in the PPI network, 10 hub genes including MAPK14, FOS, MAPK1, JUN, MYC, RELA, ESR1, STAT1, AKT1, and IL6 were selected and exhibited in Cytoscape and molecular docking. Lastly, the relation between PPI, GO, and KEGG was analyzed. These findings indicated that multiple hub network genes have been involved in behavior improvement in cerebral ischemia–reperfusion rats subjected to ZLH treatment.Conclusion: Zhilong Huoxue Tongyu capsule improves cerebral ischemia–reperfusion and is associated with multiple network gene expressions.
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spelling doaj.art-46331fce41694f0382966c5714a1d3162022-12-22T00:59:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.912392912392Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–ReperfusionNa Li0Jie Sun1Ji-Lin Chen2Xue Bai3Ting-Hua Wang4Ting-Hua Wang5Liaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaLiaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou, ChinaDepartment of Encephalopathy, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou, ChinaLiaoning Key Laboratory of Diabetic Cognitive and Perceptive Dysfunction, Jinzhou Medical University, Jinzhou, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaObjective: To investigate the effect of Zhilong Huoxue Tongyu capsule (ZLH) in the treatment of cerebral ischemia–reperfusion injury and determine the underlying molecular network mechanism.Methods: The treatment effect of Zhilong Huoxue Tongyu capsule (ZLH) was evaluated for cerebral ischemia–reperfusion injury in middle cerebral artery occlusion (MACO) rat, and the underlying molecular network mechanism was explored by using molecular network analysis based on network pharmacology, bioinformatics including protein–protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), as well as molecular docking.Results: The neurological function of rats in the ZLH group was significantly improved compared to those in the NS group (p = 0.000), confirming the positive effect of ZLH for the treatment of brain ischemia. There were 126 intersecting genes screened in ischemia–reperfusion cerebrum that are associated with several important biological processes, such as lipopolysaccharide, and the most important cell component, such as raft, as well as the most important molecular function pointed as cytokine receptor binding. The most important KEGG signaling pathway was the AGE-RAGE signaling pathway in diabetic complications. Moreover, according to the STRING interaction in the PPI network, 10 hub genes including MAPK14, FOS, MAPK1, JUN, MYC, RELA, ESR1, STAT1, AKT1, and IL6 were selected and exhibited in Cytoscape and molecular docking. Lastly, the relation between PPI, GO, and KEGG was analyzed. These findings indicated that multiple hub network genes have been involved in behavior improvement in cerebral ischemia–reperfusion rats subjected to ZLH treatment.Conclusion: Zhilong Huoxue Tongyu capsule improves cerebral ischemia–reperfusion and is associated with multiple network gene expressions.https://www.frontiersin.org/articles/10.3389/fphar.2022.912392/fullZhiLong HuoXue TongYu capsulecerebral ischemia–reperfusionnetwork pharmacologymolecular dockinggene network analysis
spellingShingle Na Li
Jie Sun
Ji-Lin Chen
Xue Bai
Ting-Hua Wang
Ting-Hua Wang
Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
Frontiers in Pharmacology
ZhiLong HuoXue TongYu capsule
cerebral ischemia–reperfusion
network pharmacology
molecular docking
gene network analysis
title Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
title_full Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
title_fullStr Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
title_full_unstemmed Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
title_short Gene Network Mechanism of Zhilong Huoxue Tongyu Capsule in Treating Cerebral Ischemia–Reperfusion
title_sort gene network mechanism of zhilong huoxue tongyu capsule in treating cerebral ischemia reperfusion
topic ZhiLong HuoXue TongYu capsule
cerebral ischemia–reperfusion
network pharmacology
molecular docking
gene network analysis
url https://www.frontiersin.org/articles/10.3389/fphar.2022.912392/full
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