scholarly journals Exploring the Regulatory Mechanism of Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound on HIF-VEGF Pathway and Cerebral Ischemia-Reperfusion Injury’s Biological Network Based on Systematic Pharmacology

2021 ◽  
Vol 12 ◽  
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yi Chen ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathways ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemic

Background: Clinical research found that Hedysarum Multijugum Maxim.-Chuanxiong Rhizoma Compound (HCC) has definite curative effect on cerebral ischemic diseases, such as ischemic stroke and cerebral ischemia-reperfusion injury (CIR). However, its mechanism for treating cerebral ischemia is still not fully explained.Methods: The traditional Chinese medicine related database were utilized to obtain the components of HCC. The Pharmmapper were used to predict HCC’s potential targets. The CIR genes were obtained from Genecards and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Finally, a series of animal experiments were carried out to further explore the mechanism of HCC intervention in CIR.Results: The prediction results of systematic pharmacology showed that HCC can regulate CIR-related targets (such as AKT1, MAPK1, CASP3, EGFR), biological processes (such as angiogenesis, neuronal axonal injury, blood coagulation, calcium homeostasis) and signaling pathways (such as HIF-1, VEGF, Ras, FoxO signaling). The experiments showed that HCC can improve the neurological deficit score, decrease the volume of cerebral infarction and up-regulate the expression of HIF-1α/VEGF and VEGFR protein and mRNA (p < 0.05).Conclusion: HCC may play a therapeutic role by regulating CIR-related targets, biological processes and signaling pathways found on this study.

The Mechanism of Gastrodin Participating in Improving the Cerebral Ischemia-Reperfusion Injury Through Notch 1 and NF-κB Signaling Pathways

2021 ◽  
Vol 11 (2) ◽  
pp. 271-275
Author(s):  
Qing Hong ◽  
Junqiang Ye ◽  
Xijia Wang ◽  
Chao Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Signaling Pathways ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Brain Area ◽  
Notch 1 ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Background: The purpose of this study was to investigate whether Gastrodin can activate the Notch 1 signaling pathway in the ischemic brain area to produce neuroprotective effects against cerebral ischemia-reperfusion injury, and to elucidate the role of Notch 1 and NF-κB signaling pathways in the Gastrodin-induced cerebral ischemic tolerance. Material and methods: The focal cerebral ischemia reperfusion model of middle cerebral artery embolism was established. TTC staining was applied to detect cerebral infarction. Tunel/NeuN immunofluorescence double labeling was employed to detect apoptosis. WB was used to detect the expressions of proteins related to the Notch 1 and NF-κB pathways. Results: Gastrodin can reduce neuron apoptosis in hippocampus after MCAO/R injury. After DAPT blocked Notch 1 signaling, the neuroprotective effects of Gastrodin improving neural function score, reducing cerebral infarction volume, and inhibiting neuronal apoptosis, were all reversed. Compared with the MCAO/R group, DAPT blocking Notch 1 signaling can also improve the neurological score of rats after MCAO/R injury, reduce cerebral infarct volume, and reduce neuronal apoptosis. Gastrodin can activate Notch 1 and NF-κB signaling pathways in cerebral ischemic areas and increase the expression of related proteins. After DAPT inhibited the Notch 1 signaling in the ipsilateral brain region, the phosphorylation level was significantly decreased, indicating that the activity of the NF-κB pathway was regulated by the Notch 1 signaling. Conclusion: Gastrodin-mediated protection against cerebral ischemia-reperfusion injury is related to the activation of Notch 1 signaling and the up-regulation of NF-κB signaling pathway activity in neurons of ischemic brain area.

scholarly journals The Effect of Hedysarum multijugum Maxim.-Chuanxiong rhizoma Compound on Ischemic Stroke: A Research Based on Network and Experimental Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-24
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yongmei Shi ◽  
Xiaofei Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Ischemic Stroke ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathways ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Buyang Huanwu Decoction

Background. Hedysarum multijugum Maxim.-Chuanxiong rhizoma compound (HCC) is a common herbal formula modified from Buyang Huanwu decoction. Clinical trials have demonstrated its therapeutic potential for ischemic stroke (IS). However, the mechanism of HCC remains unclear. Methods. The HCC’s components were collected from the TCMSP database and TCM@Taiwan database. After that, the HCC’s compound targets were predicted by PharmMapper. The IS-related genes were obtained from GeneCards, and OMIM and the protein-protein interaction (PPI) data of HCC’s targets and IS genes were obtained from the String database. After that, the DAVID platform was applied for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis and the Cytoscape 3.7.2 was utilized to construct and analyze the networks. Finally, a series of animal experiments were carried out to validate the prediction results of network pharmacology. The expressions of GRP78, p-PERK, and CHOP proteins and mRNAs in different time periods after HCC intervention were detected by Western blot, immunohistochemistry, and RT-qPCR. Results. A total of 440 potential targets and 388 IS genes were obtained. The results of HCC-IS PPI network analysis showed that HCC may regulate IS-related targets (such as ALB, AKT1, MMP9, IGF1, and CASP3), biological processes (such as endoplasmic reticulum stress, inflammation modules, hypoxia modules, regulation of neuronal apoptosis and proliferation, and angiogenesis), and signaling pathways (such as PI3K-Akt, FoxO, TNF, HIF-1, and Rap1 signaling). The animal experiments showed that HCC can improve the neurobehavioral scores and protect the neurons of IS rats ( P < 0.05 ). HCC inhibited the expression of p-PERK in the PERK pathway from 12 h after surgery, significantly promoted the expression of GRP78 protein, and inhibited the expression of CHOP protein after surgery, especially at 24 h after surgery ( P < 0.05 ). The results of RT-qPCR showed that HCC can significantly reduce the expression of CHOP mRNA in the neurons in the CA1 region of the hippocampus 72 h after MCAO ( P < 0.05 ). Conclusion. HCC may achieve a role in the treatment of IS by intervening in a series of targets, signaling pathways, and biological processes such as inflammation, oxidative stress, endoplasmic reticulum stress, and angiogenesis.

scholarly journals Exploring the Pharmacological Mechanism of Liuwei Dihuang Decoction for Diabetic Retinopathy: A Systematic Biological Strategy-Based Research

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Mengxia Yuan ◽  
Qi He ◽  
Zhiyong Long ◽  
Xiaofei Zhu ◽  
Wang Xiang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Signaling Pathways ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Ppi Network ◽  
Pharmacological Mechanism ◽  
Target Network ◽  
Erbb Signaling

Objective. To explore the pharmacological mechanism of Liuwei Dihuang decoction (LDD) for diabetic retinopathy (DR). Methods. The potential targets of LDD were predicted by PharmMapper. GeneCards and other databases were used to collect DR genes. Cytoscape was used to construct and analyze network DR and LDD’s network, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were carried out to verify the results of systematic pharmacology. Results. Five networks were constructed and analyzed: (1) diabetic retinopathy genes’ PPI network; (2) compound-compound target network of LDD; (3) LDD-DR PPI network; (4) compound-known target network of LDD; (5) LDD known target-DR PPI network. Several DR and treatment-related targets, clusters, signaling pathways, and biological processes were found. Animal experiments found that LDD can improve the histopathological changes of the retina. LDD can also increase erythrocyte filtration rate and decrease the platelet adhesion rate ( P < 0.05 ) and decrease MDA and TXB2 ( P < 0.05 ). Compared with the model group, the retinal VEGF and HIF-1α expression in the LDD group decreased significantly ( P < 0.05 ). Conclusion. The therapeutic effect of LDD on DR may be achieved by interfering with the biological processes (such as response to insulin, glucose homeostasis, and regulation of angiogenesis) and signaling pathways (such as insulin, VEGF, HIF-1, and ErbB signaling pathway) related to the development of DR that was found in this research.

Bardoxolone Ameliorates Cerebral Ischemia/ Reperfusion Injury in Male Rats

2019 ◽  
Vol 22 (04) ◽  
pp. 122-130
Author(s):  
Rihab H Al-Mudhaffer ◽  
Laith M Abbas Al-Huseini ◽  
Saif M Hassan ◽  
Najah R Hadi
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury
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