scholarly journals Systems Biology and Chemoinformatics-Based Strategies to Explore the Biological Mechanism of Fugui Wenyang Decoction in Treating Vascular Dementia Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-42
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Chuandong Cao ◽  
Haiyan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Systems Biology ◽  
Vascular Dementia ◽  
Neuronal Apoptosis ◽  
Protein Identification ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Sham Operation ◽  
Biological Mechanism ◽  
Model Group

Objective. To explore the biological mechanism of Fugui Wenyang Decoction (FGWYD) in treating vascular dementia (VD) rats based on systems pharmacology, proteomics, and a multidirectional pharmacology integration strategy. Methods. Chemoinformatics was utilized to construct and analyze the FGWYD-VD protein-protein interaction (PPI) network. Then, the total protein in the brain tissue of the infarcted side of the rat was extracted for protein identification, pattern identification, and protein quantitative analysis. The differentially expressed proteins are analyzed by bioinformatics. Finally, the important proteins in the oxidative stress-related biological process proteins and indicators were detected through experimental pharmacology to verify the findings of systems biology and chemoinformatics. Results. There were a total of 73 FGWYD components with 245 FGWYD and 145 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate the inflammation module, oxidative stress, the synaptic plasticity regulation module, and the neuronal apoptosis section module. Compared with the sham operation group, there were 23 upregulated proteins and 17 downregulated proteins in the model group ( P < 0.05 ). Compared with the model group, there were 16 upregulated proteins and 10 downregulated proteins in the FGWYD group ( P < 0.05 ). Bioinformatics analysis shows that those proteins were closely related to processes such as inflammation, oxidative stress, neuronal apoptosis, neuronal growth and differentiation, signaling pathways, and transcriptional regulation. Multidirectional pharmacology further verified the neuroprotective mechanism of the Nrf2/HO-1 pathway in FGWYD treatment of VD. Conclusion. The mechanism of FGWYD in the treatment of VD may be related to inflammation, oxidative stress, angiogenesis, and neuronal apoptosis.

scholarly journals Exploring the Oxidative Stress Mechanism of Buyang Huanwu Decoction in Intervention of Vascular Dementia Based on Systems Biology Strategy

2021 ◽  
Vol 2021 ◽  
pp. 1-29
Author(s):  
Kailin Yang ◽  
Liuting Zeng ◽  
Anqi Ge ◽  
Yaqiao Yi ◽  
Shanshan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Systems Biology ◽  
Vascular Dementia ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Buyang Huanwu Decoction ◽  
Pathway Enrichment ◽  
Go Enrichment ◽  
Go Enrichment Analysis

Objective. To explore the oxidative stress mechanism of modified Buyang Huanwu decoction (MBHD) in intervention of vascular dementia (VD) based on systems biology strategy. Methods. In this study, through the reverse virtual target prediction technology and transcriptomics integration strategy, the active ingredients and potential targets of MBHD treatment of VD were analyzed, and the drug-disease protein-protein interaction (PPI) network was constructed. Then, bioinformatics analysis methods are used for Gene Ontology (GO) enrichment analysis and pathway enrichment analysis, and finally find the core biological process. After that, in animal models, low-throughput technology is used to detect gene expression and protein expression of key molecular targets in oxidative stress-mediated inflammation and apoptosis signaling pathways to verify the mechanism of MBHD treatment of VD rats. Finally, the potential interaction relationship between MBHD and VD-related molecules is further explored through molecular docking technology. Results. There are a total of 54 MBHD components, 252 potential targets, and 360 VD genes. The results of GO enrichment analysis and pathway enrichment analysis showed that MBHD may regulate neuronal apoptosis, nitric oxide synthesis and metabolism, platelet activation, NF-κB signaling pathway-mediated inflammation, oxidative stress, angiogenesis, etc. Among them, SIRT1, NF-κB, BAX, BCL-2, CASP3, and APP may be important targets for MBHD to treat VD. Low-throughput technology (qRT-PCR/WB/immunohistochemical technology) detects oxidative stress-mediated inflammation and apoptosis-related signaling pathway molecules. The molecular docking results showed that 64474-51-7, cycloartenol, ferulic acid, formononetin, kaempferol, liquiritigenin, senkyunone, wallichilide, xanthinin, and other molecules can directly interact with NF-κB p65, BAX, BCL-2, and CASP3. Conclusion. The active compounds of MBHD interact with multiple targets and multiple pathways in a synergistic manner, and have important therapeutic effects on VD mainly by balancing oxidative stress/anti-inflammatory and antiapoptotic, enhancing metabolism, and enhancing the immune system.

scholarly journals Identification of Four Oxidative Stress-Responsive MicroRNAs, miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p, in Hepatocellular Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yong Wan ◽  
Ruixia Cui ◽  
Jingxian Gu ◽  
Xing Zhang ◽  
Xiaohong Xiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatocellular Carcinoma ◽  
Stress Response ◽  
Clinical Investigation ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Oxidative Stress Response ◽  
Rank Aggregation ◽  
Integrated Analysis ◽  
Pathway Enrichment Analysis

Increasing evidence suggests that oxidative stress plays an essential role during carcinogenesis. However, the underlying mechanism between oxidative stress and carcinogenesis remains unknown. Recently, microRNAs (miRNAs) are revealed to be involved in oxidative stress response and carcinogenesis. This study aims to identify miRNAs in hepatocellular carcinoma (HCC) cells which might involve in oxidative stress response. An integrated analysis of miRNA expression signature was performed by employing robust rank aggregation (RRA) method, and four miRNAs (miR-34a-5p, miR-1915-3p, miR-638, and miR-150-3p) were identified as the oxidative stress-responsive miRNAs. Pathway enrichment analysis suggested that these four miRNAs played an important role in antiapoptosis process. Our data also revealed miR-34a-5p and miR-1915-3p, but not miR-150-3p and miR-638, were regulated by p53 in HCC cell lines under oxidative stress. In addition, clinical investigation revealed that these four miRNAs might be involved in oxidative stress response by targeting oxidative stress-related genes in HCC tissues. Kaplan-Meier analysis showed that these four miRNAs were associated with patients’ overall survival. In conclusion, we identified four oxidative stress-responsive miRNAs, which were regulated by p53-dependent (miR-34a-5p and miR-1915-3p) and p53-independent pathway (miR-150-3p and miR-638). These four miRNAs may offer new strategy for HCC diagnosis and prognosis.

scholarly journals Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Xiang Yu ◽  
Peng Zhang ◽  
Kai Tang ◽  
Gengyang Shen ◽  
Honglin Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Signaling Pathways ◽  
Osteoporotic Fracture ◽  
Hydrophobic Interactions ◽  
Osteoclast Differentiation ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
The Core

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis ( P < 0.05 ), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included ( P < 0.05 ), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3–9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.

scholarly journals Effects of Chinese wolfberry and Astragalus extract on the antioxidant capacity of Tibetan pig liver

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245749
Author(s):  
Zhuang Hao ◽  
Zhen Li ◽  
Jinjin Huo ◽  
Jiandong Li ◽  
Fenghua Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Enrichment Analysis ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Sequencing Analysis ◽  
Lycium Barbarum ◽  
Pig Liver ◽  
Antioxidant Genes ◽  
Tibetan Pig

The objective of this study is to determine the effect of Chinese wolfberry (Lycium barbarum) and Astragalus (Astragalus membranaceus) extract (WAE) on the antioxidant capacity of Tibetan pig liver, and discussed the regulatory effect of WAE on the liver antioxidant mechanism. Twelve healthy 120-day-old Tibetan black pigs (35±2 kg) were divided randomly into two groups. The WAE group was fed a basal diet supplemented with 1% WAE for 90 days. The control group was fed the same diet, but without the WAE. We found that liver superoxide dismutase 1 (SOD1) activity (P<0.05), total antioxidative capacity (T-AOC) (P<0.05), and catalase (CAT) activity (P<0.01) significantly increased in the WAE group compared with the control group; malondialdehyde (MDA) content decreased, but this was not significant (P >0.05). Transcriptome sequencing analysis detected 106 differentially expressed genes (DEGs) related to oxidative stress. GO enrichment analysis showed these DEGs were involved in the positive regulation of reactive oxygen metabolism and biosynthesis, process regulation, and regulation of the oxidative stress response. KEGG Pathway enrichment analysis showed they were enriched in the PI3K-Akt, AMPK, Rap1, and peroxisome signaling pathways. The expression levels of key peroxisome biosynthesis genes (e.g., PEX3 and PEX11B) and key antioxidant genes (e.g., CAT and SOD1) were significantly higher in the WAE group than in the control group. The PRDX1 and PRDX5 content also was significantly higher in the WAE group. This study showed that the WAE regulated the antioxidant and anti-stress ability of Tibetan pig liver through a “peroxisome antioxidant-oxidant stress” signaling pathway.

scholarly journals Novel gene regulatory networks identified in response to nitro-conjugated linoleic acid in human endothelial cells

2019 ◽  
Vol 51 (6) ◽  
pp. 224-233 ◽  
Author(s):  
Haocheng Lu ◽  
Jinjian Sun ◽  
Wenying Liang ◽  
Jifeng Zhang ◽  
Oren Rom ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Regulatory Networks ◽  
Unsaturated Fatty Acids ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Human Coronary Artery

Endothelial cell (EC) dysfunction is a crucial initiation event in the development of atherosclerosis and is associated with diabetes mellitus, hypertension, and heart failure. Both digestive and oxidative inflammatory conditions lead to the endogenous formation of nitrated derivatives of unsaturated fatty acids (FAs) upon generation of the proximal nitrating species nitrogen dioxide (·NO2) by nitric oxide (·NO) and nitrite-dependent reactions. Nitro-FAs (NO2-FAs) such as nitro-oleic acid (NO2-OA) and nitro-linoleic acid (NO2-LA) potently inhibit inflammation and oxidative stress, regulate cellular functions, and maintain cardiovascular homeostasis. Recently, conjugated linoleic acid (CLA) was identified as the preferential FA substrate of nitration in vivo. However, the functions of nitro-CLA (NO2-CLA) in ECs remain to be explored. In the present study, a distinct transcriptome regulated by NO2-CLA was revealed in primary human coronary artery endothelial cells (HCAECs) through RNA sequencing. Differential gene expression and pathway enrichment analysis identified numerous regulatory networks including those related to the modulation of inflammation, oxidative stress, cell cycle, and hypoxic responses by NO2-CLA, suggesting a diverse impact of NO2-CLA and other electrophilic nitrated FAs on cellular processes. These findings extend the understanding of the protective actions of NO2-CLA in cardiovascular diseases and provide new insight into the underlying mechanisms that mediate the pleiotropic cellular responses to NO2-CLA.

scholarly journals Network Pharmacology-Based Investigation of Potential Targets of Astragalus-Angelica Compound Acting on Diabetic Nephropathy

2021 ◽  
Author(s):  
Youzi Dong ◽  
Quanlin Zhao
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Molecular Docking ◽  
Kegg Pathway ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Target Protein ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment

Abstract Through network pharmacology and molecular docking to explore the mechanism of astragalus-angelica compound in the treatment of diabetic nephropathy (DN). Screen the components and targets of astragalus and angelica compound on the TCMSP and the BATMAN-TCM, and use Cytoscape 3.7.2 to establish a component-target interaction network. Relevant targets of DN were searched through related databases, and the common targets of astragalus-angelica compound prescription and DN were obtained after comparison. The target protein interaction analysis and visualization processing were performed, and gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through David database, and molecular docking was performed using PyMoL and AutoDock Vina software. Through network pharmacology screening, 142 main targets of astragalus-angelica compound in the treatment of DN have been identified. KEGG pathway enrichment analysis shows that the above key targets are related to apoptosis, oxidative stress, inflammation, insulin resistance and other related pathways. Molecular docking shows that the target protein has a good combination with the main active ingredients of astragalus-angelica compound. Astragalus-angelica compound may act on VEGFA, TP53, IL-6, TNF, mark1 and other targets to treat DN by regulating apoptosis, oxidative stress, inflammation, glucose and lipid metabolism and other pathways. Research methods based on network pharmacology and molecular docking provide new ideas for the pathogenesis and treatment of DN.

scholarly journals Network pharmacology-based investigation of potential targets of astragalus membranaceous-angelica sinensis compound acting on diabetic nephropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Youzi Dong ◽  
Quanlin Zhao ◽  
Yuguo Wang
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Molecular Docking ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Angelica Sinensis ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment

AbstractTo explore the mechanism of the Astragalus membranaceous (AM)-Angelica sinensis (AS) compound in the treatment of diabetic nephropathy (DN) we used network pharmacology and molecular docking. Screen the components and targets of the AM-AS compound in the TCMSP and the BATMAN-TCM, and establish a component-target interaction network by Cytoscape 3.7.2. After searching relevant targets of DN in related databases, the common targets of the AM-AS compound and DN were obtained by comparison. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through David database. Molecular docking was performed by PyMoL2.3.0 and AutoDock Vina software. After screening, 142 main targets of the AM-AS compound in the treatment of DN have been identified. Target network was established and the topology of PPI network was analyzed. KEGG pathway enrichment analysis shows that these targets are related to apoptosis, oxidative stress, inflammation, insulin resistance, etc. Molecular docking shows that the target proteins have good combinations with the main active components of the AM-AS compound. AM-AS compound may treat DN by acting on VEGFA, TP53, IL-6, TNF, MARK1, etc., and regulate apoptosis, oxidative stress, inflammation, glucose, and lipid metabolism processes. The in vivo study results suggest that AM-AS compound can significantly reduce the FBG level of diabetic rats, increase the level of INS, improve renal functions, reduce urinary proteins, inhibit glycogen deposition, granulocyte infiltration and collagen fiber proliferation in renal tissue, and restrain the progress of DN. In vivo study combined with network pharmacology and molecular docking methods provides new ideas for the pathogenesis and treatments of DN.

A Method of Pathway Enrichment Analysis Based Gene Expression Variability

2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Expression Variability ◽  
Pathway Enrichment
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