scholarly journals Systems Pharmacological Approach to Investigate the Mechanism of Acori Tatarinowii Rhizoma for Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Zhenyan Song ◽  
Fang Yin ◽  
Biao Xiang ◽  
Bin Lan ◽  
Shaowu Cheng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Biological Processes ◽  
Pathway Enrichment ◽  
Study Results ◽  
Target Network ◽  
Anti Inflammatory

In traditional Chinese medicine (TCM), Acori Tatarinowii Rhizoma (ATR) is widely used to treat memory and cognition dysfunction. This study aimed to confirm evidence regarding the potential therapeutic effect of ATR on Alzheimer’s disease (AD) using a system network level based in silico approach. Study results showed that the compounds in ATR are highly connected to AD-related signaling pathways, biological processes, and organs. These findings were confirmed by compound-target network, target-organ location network, gene ontology analysis, and KEGG pathway enrichment analysis. Most compounds in ATR have been reported to have antifibrillar amyloid plaques, anti-tau phosphorylation, and anti-inflammatory effects. Our results indicated that compounds in ATR interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by ATR are elevated significantly in heart, brain, and liver. Our results suggest that the anti-inflammatory and immune system enhancing effects of ATR might contribute to its major therapeutic effects on Alzheimer’s disease.

scholarly journals Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer’s Disease

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1499 ◽  
Author(s):  
Yi-wei Sun ◽  
Yue Wang ◽  
Zi-feng Guo ◽  
Kai-cheng Du ◽  
Da-li Meng
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Large Numbers ◽  
Brain Barrier Permeability ◽  
Target Network ◽  
Synergistic Mechanism

Ohwia caudata (OC)—a traditional Chinese medicine (TCM)—has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer’s disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood–brain barrier permeability against AD, by using a system network level-based in silico approach. The results revealed that two new flavonoids, and another 26 compounds isolated from OC in our lab, were highly connected to AD-related signaling pathways and biological processes, which were confirmed by compound–target network, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, respectively. Predicted by the virtual screening and various network pharmacology methods, we found the multiple mechanisms of OC, which are effective for alleviating AD symptoms through multiple targets in a synergetic way.

scholarly journals MicroRNA-Target Interaction Regulatory Network in Alzheimer’s Disease

2021 ◽  
Vol 11 (12) ◽  
pp. 1275
Author(s):  
Aleksander Turk ◽  
Tanja Kunej ◽  
Borut Peterlin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Microrna Target ◽  
Target Interaction ◽  
Pathway Enrichment ◽  
Protein Protein Interaction

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on miRNA–target interactions (MTI) associated with AD are scattered across databases and publications, thus making the identification of promising miRNA biomarkers for AD difficult. In response to this, a list of experimentally validated AD-associated MTIs was obtained from miRTarBase. Cytoscape was used to create a visual MTI network. STRING software was used for protein–protein interaction analysis and mirPath was used for pathway enrichment analysis. Several targets regulated by multiple miRNAs were identified, including: BACE1, APP, NCSTN, SP1, SIRT1, and PTEN. The miRNA with the highest numbers of interactions in the network were: miR-9, miR-16, miR-34a, miR-106a, miR-107, miR-125b, miR-146, and miR-181c. The analysis revealed seven subnetworks, representing disease modules which have a potential for further biomarker development. The obtained MTI network is not yet complete, and additional studies are needed for the comprehensive understanding of the AD-associated miRNA targetome.

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

scholarly journals Soluble Amyloid-Beta Isoforms Predict Downstream Alzheimer’s Disease Pathology

2021 ◽  
Author(s):  
Guilherme Povala ◽  
Bruna Bellaver ◽  
Marco Antônio De Bastiani ◽  
Wagner S. Brum ◽  
Pamela C. L. Ferreira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Area Under The Curve ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Biological Processes ◽  
Proteomics Data ◽  
Proteomics Analysis ◽  
Significant Enrichment

Abstract Background: Changes in soluble amyloid-beta (Aβ) levels in cerebrospinal fluid (CSF) are detectable at early preclinical stages of Alzheimer's disease (AD). However, whether Aβ levels can predict downstream AD pathological features in cognitively unimpaired (CU) individuals remains unclear. With this in mind, we aimed at investigating whether a combination of soluble Aβ isoforms can predict tau pathology (T+) and neurodegeneration (N+) positivity. Methods: We used CSF measurements of three soluble Aβ peptides (Aβ1‑38, Aβ1‑40 and Aβ1‑42) in CU individuals (n = 318) as input features in machine learning (ML) models aiming at predicting T+ and N+. Input data was used for building 2046 tuned predictive ML models with a nested cross-validation technique. Additionally, proteomics data was employed to investigate the functional enrichment of biological processes altered in T+ and N+ individuals. Results: Our findings indicate that Aβ isoforms can predict T+ and N+ with an area under the curve (AUC) of 0.929 and 0.936, respectively. Additionally, proteomics analysis identified 17 differentially expressed proteins (DEPs) in individuals wrongly classified by our ML algorithm. More specifically, enrichment analysis of gene ontology biological processes revealed an upregulation in myelinization and glucose metabolism-related processes in CU individuals wrongly predicted as T+. A significant enrichment of DEPs in pathways including biosynthesis of amino acids, glycolysis/gluconeogenesis, carbon metabolism, cell adhesion molecules and prion disease was also observed. Conclusions: Our results demonstrate that, by applying a refined ML analysis, a combination of Ab isoforms can predict T+ and N+ with a high AUC. CSF proteomics analysis highlighted a promising group of proteins that can be further explored for improving T+ and N+ prediction.

scholarly journals Neuroprotective and Anti-Inflammatory Effects of Low–Moderate Dose Ionizing Radiation in Models of Alzheimer’s Disease

2020 ◽  
Vol 21 (10) ◽  
pp. 3678 ◽  
Author(s):  
Sujin Kim ◽  
Yunkwon Nam ◽  
Chanyang Kim ◽  
Hyewon Lee ◽  
Seojin Hong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Ionizing Radiation ◽  
Pharmacological Intervention ◽  
Therapeutic Effects ◽  
Moderate Dose ◽  
Short Term ◽  
Anti Inflammatory ◽  
5Xfad Mice

Alzheimer’s disease (AD) is the most common cause of dementia. The neuropathological features of AD include amyloid-β (Aβ) deposition and hyperphosphorylated tau accumulation. Although several clinical trials have been conducted to identify a cure for AD, no effective drug or treatment has been identified thus far. Recently, the potential use of non-pharmacological interventions to prevent or treat AD has gained attention. Low-dose ionizing radiation (LDIR) is a non-pharmacological intervention which is currently being evaluated in clinical trials for AD patients. However, the mechanisms underlying the therapeutic effects of LDIR therapy have not yet been established. In this study, we examined the effect of LDIR on Aβ accumulation and Aβ-mediated pathology. To investigate the short-term effects of low–moderate dose ionizing radiation (LMDIR), a total of 9 Gy (1.8 Gy per fraction for five times) were radiated to 4-month-old 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD, and then sacrificed at 4 days after last exposure to LMDIR. Comparing sham-exposed and LMDIR-exposed 5XFAD mice indicated that short-term exposure to LMDIR did not affect Aβ accumulation in the brain, but significantly ameliorated synaptic degeneration, neuronal loss, and neuroinflammation in the hippocampal formation and cerebral cortex. In addition, a direct neuroprotective effect was confirmed in SH-SY5Y neuronal cells treated with Aβ1–42 (2 μM) after single irradiation (1 Gy). In BV-2 microglial cells exposed to Aβ and/or LMDIR, LMDIR therapy significantly inhibited the production of pro-inflammatory molecules and activation of the nuclear factor-kappa B (NF-κB) pathway. These results indicate that LMDIR directly ameliorated neurodegeneration and neuroinflammation in vivo and in vitro. Collectively, our findings suggest that the therapeutic benefits of LMDIR in AD may be mediated by its neuroprotective and anti-inflammatory effects.

scholarly journals Systems Pharmacological Approach of Pulsatillae Radix on Treating Crohn’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-21 ◽  
Author(s):  
Su Yeon Suh ◽  
Won G. An
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Biological Processes ◽  
Gene Ontology Analysis ◽  
Pathway Network ◽  
Amoebic Dysentery ◽  
Study Results ◽  
Target Network ◽  
Anti Inflammatory ◽  
Antioxidant Effects

In East Asian traditional medicine, Pulsatillae Radix (PR) is widely used to treat amoebic dysentery and renowned for its anti-inflammatory effects. This study aimed to confirm evidence regarding the potential therapeutic effect of PR on Crohn’s disease using a system network level based in silico approach. Study results showed that the compounds in PR are highly connected to Crohn’s disease related pathways, biological processes, and organs, and these findings were confirmed by compound-target network, target-pathway network, and gene ontology analysis. Most compounds in PR have been reported to possess anti-inflammatory, anticancer, and antioxidant effects, and we found that these compounds interact with multiple targets in a synergetic way. Furthermore, the mRNA expressions of genes targeted by PR are elevated significantly in immunity-related organ tissues, small intestine, and colon. Our results suggest that the anti-inflammatory and repair and immune system enhancing effects of PR might have therapeutic impact on Crohn’s disease.

scholarly journals Network Pharmacology Study of Heat-Clearing and Detoxifying Traditional Chinese Medicine for Alzheimer's Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hongxing Li ◽  
Xinyue Zhang ◽  
Lili Gu ◽  
Ningzi Wu ◽  
Lingxi Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Chlorogenic Acid ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis

This study aims to explore the possible homologous mechanism of 7 frequently‐used herbs for heat-clearing and detoxification in traditional Chinese medicine (HDTCM) for treating Alzheimer's disease (AD), one of the most common types of dementia, based on network pharmacology. Herbs that satisfied the criteria of containing chlorogenic acid, relating to AD and aligning with HDTCM, were simultaneously collected to determine whether they have anti-AD effect based on a survey of the literature. Herb-ingredient-target-disease networks were constructed by collecting information from the TCMSP and GeneCards public databases. The common targets of the herbs and AD were identified for conducting a Gene Ontology (GO) analyses and a Reactome pathway enrichment analysis. The results showed that PTGS1, IL-6, CASP3, and VEGFA were the predicted key gene targets. The IL-4 and IL-13 signaling pathway, the ESR-mediated signaling pathway, and the extranuclear estrogen signaling pathway were the significant pathways associated with the 7 herbs. This study revealed that the analogous anti-AD mechanism of the 7 herbs of HDTCM may be associated with anti-inflammation, which is a common effect of the chlorogenic acid and quercetin components.

scholarly journals Novel Biomarker MicroRNAs for Subtyping of Acute Coronary Syndrome: A Bioinformatics Approach

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Yujie Zhu ◽  
Yuxin Lin ◽  
Wenying Yan ◽  
Zhandong Sun ◽  
Zhi Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Coronary Syndrome ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Pathway Enrichment ◽  
Coronary Syndrome ◽  
Life Threatening

Acute coronary syndrome (ACS) is a life-threatening disease that affects more than half a million people in United States. We currently lack molecular biomarkers to distinguish the unstable angina (UA) and acute myocardial infarction (AMI), which are the two subtypes of ACS. MicroRNAs play significant roles in biological processes and serve as good candidates for biomarkers. In this work, we collected microRNA datasets from the Gene Expression Omnibus database and identified specific microRNAs in different subtypes and universal microRNAs in all subtypes based on our novel network-based bioinformatics approach. These microRNAs were studied for ACS association by pathway enrichment analysis of their target genes. AMI and UA were associated with 27 and 26 microRNAs, respectively, nine of them were detected for both AMI and UA, and five from each subtype had been reported previously. The remaining 22 and 21 microRNAs are novel microRNA biomarkers for AMI and UA, respectively. The findings are then supported by pathway enrichment analysis of the targets of these microRNAs. These novel microRNAs deserve further validation and will be helpful for personalized ACS diagnosis.

Sign in / Sign up

Export Citation Format

Share Document