scholarly journals Identifying mechanisms of Epimedii Folium against Alzheimer’s disease via a network pharmacology approach Epimedii Folium treats Alzheimer’s disease via PI3K-AKT

2021 ◽  
Vol 19 ◽  
pp. 205873922110414
Author(s):  
Yan Zhao ◽  
Guangmei Liu ◽  
Yang Yang ◽  
Ling Chen ◽  
Ying Shang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Target Therapy ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Pathway Gene

To elucidate the mechanism of the multi-target action of Epimedii Folium on Alzheimer’s disease, this study focuses on the analysis of network pharmacology. Based on a bioinformatics approach, this study obtained the effective components of Epimedium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, predicted the compound targets through the Pharmapper and Swiss target prediction database and then through Gene Expression Omnibus Datasets and Therapeutic Target Database. We collected and analysed of heral and disease targets, constructed the network. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology enrichment, then the key targets and pathways of Epimedii Folium to cope with Alzheimer’s disease have been identified. Twenty-three bioactive components and 477 potential target genes of Epimedii Folium were identified. A total of 1612 target diseases were identified. Through network module analysis, 30 hub target genes were identified. Through enrichment analysis of the KEGG pathway, hub target genes were largely enriched in the PI3K-AKT signaling pathway. Through the analysis of network pharmacology, it was found that Epimedii Folium might play the role of multi-compound and multi-target therapy through the PI3K-AKT signaling pathway. These findings provide helpful directions for future clinical studies.

Identification and Functional Analysis of Serum Specific MiRNAs in Patients with Recurrent Aphthous Somatitis of Excess-heat or Yin-deficiency Syndrome

2019 ◽  
Author(s):  
Jie Bao ◽  
Zhengyang Zhu ◽  
Xizhao Zhang ◽  
Lin Huang ◽  
Li Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Kegg Pathway ◽  
Deficiency Syndrome ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Excess Heat ◽  
Yin Deficiency ◽  
Heat Syndrome

Abstract Background. MiRNAs has become an important regulator in many processes. The purpose of our study is to screen the key serum miRNAs of different syndrome of recurrent aphthous stomatitis (RAS), to find new biomarkers for the diagnosis of RAS and to further explore their role in the pathogenesis of RAS.Method. Serum samples were collected from patients meeting the RAS diagnostic criteria of excess-heat or yin-deficiency syndrome and healthy individuals. Core miRNAs were then identified under miRNA microarray analyses. Target prediction and bioinformatic analyses were carried out and gene-pathway-networks were visualized to better understand the relationship between different genes and pathways.Result. (1) 90 individuals meeting the inclusion criteria were collected in this study, of which 30 were normal control, 30 were patients of excess-heat syndrome and the rest were patients of yin-deficiency syndrome. Among them, 9 miRNAs were screened out in excess-heat syndrome group, with 1 upregulated and 8 downregulated. And four random miRNAs (hsa-miR-20b-5p, hsa-miR-122-5p, hsa-miR-483-5p and hsa-miR-3197) were validated by real-time PCR method. 14 miRNAs were screened out in yin-deficiency syndrome group (7 upregulated and 7 downregulated). And hsa-miR-17-5p, hsa-miR-106-5p and hsa-miR-20b-5p were validated. (2) A total of 4776 target genes were identified for the validated 9 miRNAs in excess-heat syndrome group. These targets were enriched in GO categories including nervous system development, homophilic cell adhesion via plasma membrane adhesion molecules, and calcium ion binding and KEGG pathway such as proteoglycans in cancer, P13K-AKT signaling pathway and Calcium signaling pathway. 10172 target genes were identified for the validated 14 miRNAs in yin-deficiency syndrome group. The enriched GO categories included protein binding, positive regulation of transcription from RNA polymerase II promoter and membrane and enriched KEGG pathway included pathways in cancer, MAPK signaling pathway and Ras signaling pathway .Conclusion. Hsa-miR-20b-5p in patients with RAS could act as the novel biomarker for clinical diagnosis of the disease. It is upregulated in RAS patients of excess-heat syndrome while downregulated in patients of yin-deficiency syndrome. The PI3K-Akt signaling pathway and MAPK signaling pathway and related target genes may provide new insights into the molecular mechanisms of excess-heat syndrome and yin-deficiency syndrome RAS, respectively.

scholarly journals Integrated Genomic Analysis Highlights the Impaired PI3K-Akt Signaling Pathway in Alzheimer’s Disease

2021 ◽  
Vol 12 (2) ◽  
pp. 2332-2339
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Meta Analysis ◽  
Temporal Cortex ◽  
Genomic Analysis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Underlying Mechanisms ◽  
Treatment And Diagnosis

Alzheimer’s disease (AD), a leading cause of dementia, remained incurable, despite many advances in our knowledge about AD pathogenesis, underlying mechanisms are poorly understood. Transcriptome analysis showed efficiency in exploring these mechanisms; however, data are generated at a higher pace than interpreted and are almost inconsistent. Therefore we performed this meta-analysis to extract new knowledge from existing data and find the mechanisms involved in AD. Five temporal cortex transcriptomics datasets from 187 AD patients and 167 healthy controls were analyzed. Our analysis showed that the PI3K-Akt signaling pathway is significantly impaired in AD brains and was common among all datasets. Moreover, miRs targeting genes involved in the PI3K-Akt signaling pathway were identified. In conclusion, our results highlight the impaired PI3K-Akt signaling pathway in AD and suggested related miRs as the potential targets for early treatment and diagnosis of AD.

scholarly journals Mechanism of Modified Danggui Sini Decoction for Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Chaoqun Feng ◽  
Min Zhao ◽  
Leiming Jiang ◽  
Ziang Hu ◽  
Xiaohong Fan
Keyword(s):  
Molecular Docking ◽  
Inflammatory Response ◽  
Knee Osteoarthritis ◽  
Signaling Pathway ◽  
Cellular Response ◽  
Kegg Pathway ◽  
Akt Signaling ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Akt Signaling Pathway

Objective. This study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking. Methods. The main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of “drugs-active components-disease targets” was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software. Results. Seventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities. Conclusion. Modified Danggui Sini Decoction has the hierarchical network characteristics of “multicomponent, multitarget, multifunction, and multipathway” in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.

scholarly journals PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui-Zhi Long ◽  
Yan Cheng ◽  
Zi-Wei Zhou ◽  
Hong-Yu Luo ◽  
Dan-Dan Wen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Natural Products ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gsk 3Β

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3β (GSK-3β), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.

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