Dataset Information

Genes Induced by Panax Notoginseng in a Rodent Model of Ischemia-Reperfusion Injury.

ABSTRACT: Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN's neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.

SUBMITTER: Meng L

PROVIDER: S-EPMC7714582 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Genes Induced by Panax Notoginseng in a Rodent Model of Ischemia-Reperfusion Injury.

Meng Lanqing L Huang Qing Q Li Xuebin X Liang Ping P Li Yueyong Y Huang Xiaohua X Zhao Jingjie J Chen Qiuping Q Qiu Rong R Li Lan L Jian Chongdong C Yao Hongfei H Huang Jianmin J Tang Xionglin X Wang Zechen Z Wei Zhongheng Z Wu Jun J Wei Liuzhi L Wei Qiuju Q Tang Qianli Q Huang Lu L Wei Jihua J Lu Dinggui D Luo Qunqiang Q Xie Kegong K Ouyang Yang Y Chen Jian J Li Genliang G Luo Linxue L He Linbo L Zhuo Chenyi C Xu Anding A Meng Lingzhang L

Journal of immunology research 20201125

Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used ...[more]

PMID: 33294469

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Project description:Objective: We aimed to explore the protective effect of Panax notoginseng rhizomes (PNR) on renal ischemia and reperfusion injury (RIRI) and the underlying molecular network mechanism based on network pharmacology and combined systemic experimental validation. Methods: A bilateral RIRI model was established, and Cr, SCr, and BUN levels were detected. Then, the PNR was pretreated 1 week before the RIRI model was prepared. To determine the effects of the PNR in RIRI, histopathological damage and the effect of PNRs to the kidney was assessed, using TTC, HE, and TUNEL staining. Furthermore, the underlying network pharmacology mechanism was detected by screening drug-disease intersection targets from PPI protein interactions and GO and KEGG analysis, and the hub genes were screened for molecular docking based on the Degree value. Finally, the expression of hub genes in kidney tissues was verified by qPCR, and the protein expression of related genes was further detected by Western blot (WB). Results: PNR pretreatment could effectively increase Cr level, decrease SCr and BUN levels, reduce renal infarct areas and renal tubular cell injury areas, and inhibit renal cell apoptosis. By using network pharmacology combined with bioinformatics, we screened co-targets both Panax notoginseng (Sanchi) and RIRI, acquired ten hub genes, and successfully performed molecular docking. Of these, pretreatment with the PNR reduced the mRNA levels of IL6 and MMP9 at postoperative day 1 and TP53 at postoperative day 7, and the protein expression of MMP9 at postoperative day 1 in IRI rats. These results showed that the PNR could decrease kidney pathological injury in IRI rats and inhibit apoptotic reaction and cell inflammation so as to improve renal injury effectively, and the core network mechanism is involved in the inhibition of MMP9, TP53, and IL-6. Conclusion: The PNR has a marked protective effect for RIRI, and the underlying mechanism is involved in inhibiting the expression of MMP9, TP53, and IL-6. This striking discovery not only provides fruitful evidence for the protective effect of the PNR in RIRI rats but also provides a novel mechanic explanation.

Project description:Panax notoginseng mixture (PNM) has the characteristics of multicomponent, multitarget, and multieffect, which can cope with the multidirectional and multidimensional complex pathological process caused by hepatic ischemia/reperfusion injury (HIRI). Our animal experiments showed that PNM composed of notoginseng, dogwood, and white peony root could significantly reduce the level of aspartate transaminase and alanine aminotransferase in the blood of mice with HIRI, indicating that this preparation had a protective effect on HIRI in mice. Therefore, on this basis, the molecular mechanism of PNM intervention in HIRI was further explored by network pharmacology. First, target genes corresponding to active components and HIRI were obtained through databases such as TCMSP, Pharm Mapper, Swiss Target Prediction, GeneCards, and so on. All target genes were standardized by Uniprot database, and a total of 291 target genes with their intersection were obtained. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and biological processes (BPs) of 291 target genes were obtained through the online public platform of DAVID. A total of 177 KEGG pathways and 337 BPs were obtained by setting p < 0.01 and false discovery rate <0.05. The network mapping map of components and disease targets was drawn by Cytoscape, and the top 10 Hub target genes related to HIRI were obtained. At the same time, the String database was used to obtain the protein-protein interaction dataset, which was imported into Cytoscape, and the first 10 Hub target genes were obtained. The Hub target genes obtained by the above two methods were molecular docking with their corresponding small molecule compounds through DockThor online tool. The results showed that the docking of paeoniflorin with glyceraldehyde 3-phosphate dehydrogenase (GAPDH), paeoniflorin and loganin with SRC, ginsenoside Rb1 with NR3C2, ursolic acid and oleanolic acid with IL-6, paeoniflorin docking VEGFA, and MMP9. Finally, NR3C2, SRC, and GAPDH were identified as target genes in this study by referring to relevant literature reports. After verification by immunohistochemical experiments, compared with the sham group, the above three target genes were highly expressed in the HIRI group (p < 0.01). Compared with the HIRI group, the expression of three target genes in the PNM + HIRI group was significantly decreased (p < 0.01). The results showed that PNM could protect mouse HIRI by decreasing the expression of NR3C2, SRC, and GAPDH.

Project description:Background: Acute kidney injury (AKI) is a severe clinical syndrome, and ischemia-reperfusion injury is an important cause of acute kidney injury. The aim of the present study was to investigate the related genes and pathways in the mouse model of acute kidney injury induced by ischemia-reperfusion injury (IRI-AKI). Method: Two public datasets (GSE39548 and GSE131288) originating from the NCBI Gene Expression Omnibus (GEO) database were analyzed using the R software limma package, and differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) and gene set enrichment analysis (GSEA) were performed using the differentially expressed genes. Furthermore, a protein-protein interaction (PPI) network was constructed to investigate hub genes, and transcription factor (TF)-hub gene and miRNA-hub gene networks were constructed. Drugs and molecular compounds that could interact with hub genes were predicted using the DGIdb. Result: A total of 323 common differentially expressed genes were identified in the renal ischemia-reperfusion injury group compared with the control group. Among these, 260 differentially expressed genes were upregulated and 66 differentially expressed genes were downregulated. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis results showed that these common differentially expressed genes were enriched in positive regulation of cytokine production, muscle tissue development, and other biological processes, indicating that they were involved in mitogen-activated protein kinase (MAPK), PI3K-Akt, TNF, apoptosis, and Epstein-Barr virus infection signaling pathways. Protein-protein interaction analysis showed 10 hub genes, namely, Jun, Stat3, MYC, Cdkn1a, Hif1a, FOS, Atf3, Mdm2, Egr1, and Ddit3. Using the STRUST database, starBase database, and DGIdb database, it was predicted that 34 transcription factors, 161 mi-RNAs, and 299 drugs or molecular compounds might interact with hub genes. Conclusion: Our findings may provide novel potential biomarkers and insights into the pathogenesis of ischemia-reperfusion injury-acute kidney injury through a comprehensive analysis of Gene Expression Omnibus data, which may provide a reliable basis for early diagnosis and treatment of ischemia-reperfusion injury-acute kidney injury.

Dataset Information

Genes Induced by Panax Notoginseng in a Rodent Model of Ischemia-Reperfusion Injury.

Publications

Genes Induced by Panax Notoginseng in a Rodent Model of Ischemia-Reperfusion Injury.

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