scholarly journals Biodata Mining-based Elucidation of Mechanisms of Hesperetin as a Candidate for Atherosclerosis

2020 ◽  
Author(s):  
Lianzhou Huang ◽  
Zexiu Huang ◽  
Yuanqiu Chen ◽  
Xin Jin ◽  
Ji Xiao ◽  
...  
Keyword(s):  
Active Ingredient ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Biological Activities ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Citrus Aurantium ◽  
Wide Range ◽  
Anti Inflammatory

Abstract BackgroundHesperetin, an active ingredient derived from Citrus × aurantium L., possesses a wide range of biological activities, including anti-inflammatory, anti-oxidation, and anti-cancer activity. Notably, hesperetin has been proposed as a candidate for atherosclerosis owing to the lipid-regulating and anti-inflammatory effect, while the underlying mechanisms remains obscure.ResultsIn our present study, the pharmacological and molecular properties of hesperetin were first evaluated to determine the druggability of hesperetin. Subsequently, 53 hesperetin-atherosclerosis crossover targets were collected to establish the protein-protein interaction network. The result of Gene Ontology enrichment analysis indicated that the crossover targets were involved in the regulation of lipid metabolism and inflammatory response. Moreover, the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that the crossover targets were highly correlated with the pathogenesis of atherosclerosis, such as fluid shear stress and atherosclerosis pathway and the TNF signaling pathway. Finally, an entire hesperetin-target-pathway network was constructed to provide a systematic overview of the pharmacological mechanisms of action of hesperetin against atherosclerosis.ConclusionsThe pharmacological mechanisms of actions of hesperetin against atherosclerosis was unveiled based on biodata mining from the public database and the bioinformatics data analysis-based strategy in this study, contributing to a deeper understanding of the molecular mechanisms of hesperetin in the treatment of atherosclerosis. Based on the results of network pharmacology analysis, we can conclude that hesperetin is surely an excellent candidate for atherosclerosis. We believe our work would be beneficial for further research and development of hesperetin as a natural active ingredient derived from Citrus × aurantium L. for the treatment of atherosclerosis.

scholarly journals A Network Pharmacology Approach to Uncover the Mechanisms of Shen-Qi-Di-Huang Decoction against Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Sha Di ◽  
Lin Han ◽  
Qing Wang ◽  
Xinkui Liu ◽  
Yingying Yang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interaction ◽  
Regulation Of Blood Pressure ◽  
Protein Protein Interaction Network

Shen-Qi-Di-Huang decoction (SQDHD), a well-known herbal formula from China, has been widely used in the treatment of diabetic nephropathy (DN). However, the pharmacological mechanisms of SQDHD have not been entirely elucidated. At first, we conducted a comprehensive literature search to identify the active constituents of SQDHD, determined their corresponding targets, and obtained known DN targets from several databases. A protein-protein interaction network was then built to explore the complex relations between SQDHD targets and those known to treat DN. Following the topological feature screening of each node in the network, 400 major targets of SQDHD were obtained. The pathway enrichment analysis results acquired from DAVID showed that the significant bioprocesses and pathways include oxidative stress, response to glucose, regulation of blood pressure, regulation of cell proliferation, cytokine-mediated signaling pathway, and the apoptotic signaling pathway. More interestingly, five key targets of SQDHD, named AKT1, AR, CTNNB1, EGFR, and ESR1, were significant in the regulation of the above bioprocesses and pathways. This study partially verified and predicted the pharmacological and molecular mechanisms of SQDHD on DN from a holistic perspective. This has laid the foundation for further experimental research and has expanded the rational application of SQDHD in clinical practice.

scholarly journals Deciphering of Key Pharmacological Pathways of Poria Cocos Intervention in Breast Cancer Based on Integrated Pharmacological Method

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Xiaoran Ma ◽  
Jibiao Wu ◽  
Cun Liu ◽  
Jie Li ◽  
Shixia Dong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Network Pharmacology ◽  
Breast Cancers ◽  
Active Ingredients ◽  
Poria Cocos ◽  
Pharmacological Method

Objective. Poria cocos (Fuling), a natural plant, has recently emerged as a promising strategy for cancer treatment. However, the molecular mechanisms of Poria cocos action in breast cancer remain poorly understood. Methods. TCMSP database was used to screen the potential active ingredients in Poria cocos. GEO database was used to identify differentially expressed genes. Network pharmacology was used to identify the specific pathways and key target proteins related to breast cancer. Finally, molecular docking was used to validate the results. Results. In our study, 237 targets were predicted for 15 potential active ingredients found in Poria cocos. An interaction network of predicted targets and genes differentially regulated in breast cancers was constructed. Based on the constructed network and further analysis including network topology, KEGG, survival analysis, and gene set enrichment analysis, 3 primary nodes were identified as key potential targets that were significantly enriched in the PPAR signaling pathway. Conclusion. The results showed that potential active ingredients of Poria cocos might interfere with breast cancer through synergistic regulation of PTGS2, ESR1, and FOS.

scholarly journals A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yi-Zi Xie ◽  
Chen-Wen Peng ◽  
Zu-Qing Su ◽  
Hui-Ting Huang ◽  
Xiao-Hong Liu ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Biological Activities ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
World Health ◽  
Drug Candidate ◽  
Potential Threat ◽  
System Pharmacology

Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein–protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K–AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible “dangerous liaison” between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.

scholarly journals Network Pharmacological Study of Achyranthis bidentatae Radix Effect on Bone Trauma

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Liying Wu ◽  
Youguo Hao ◽  
Chuanqiang Dai ◽  
Zhibang Zhang ◽  
Munazza Ijaz ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Pharmacological Study ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Docking Studies ◽  
Network Pharmacology ◽  
Extensive Literature ◽  
Positive Regulation ◽  
Oxidoreductase Activity ◽  
Bone Trauma

Purpose. Bone trauma is a clinical condition that afflicts the majority of the world’s population. For the management of bone trauma, the underlying mechanisms of the drugs effective for bone healing are deemed necessary. Achyranthis bidentatae Radix (ABR) is a popular alternative medicine recommended in the treatment of bone trauma and injury, yet its mechanism of action persists to be vague. This study was conducted for the evaluation of the mode of action of ABR through network pharmacology in treating bone trauma. Methods. An extensive survey of published works led to the development of a drug-target database, after which multiple protein targets for bone trauma were discerned. The protein-protein interaction network was developed by utilizing the STITCH database and gene ontology (GO) enrichment analysis using Cytoscape and ClueGO. Moreover, docking studies were performed for revealing the affinity of various ingredients with IL6. Results. The extensive literature survey yielded the presence of 176 components in ABR, and 151 potential targets were acquired. Scrutinization of these targets revealed that 21 potential targets were found to be associated with bone trauma. Out of which, some remarkable targets such as IL6, MAPK14, MAPK8, SRC, PTGS2, and MMP2 were observed to be associated in the functional interaction of ABR. According to docking results, several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have the lowest docking scores (range between -6 and -7). Conclusions. The results of the study elucidated that ABR can positively be utilized for the management of bone trauma, which can be mediated by multiple molecular mechanisms such as ERBB2 signaling pathway, positive regulation of oxidoreductase activity, JNK cascade pathway, multicellular organism metabolic process, T cell costimulation, and the positive regulation of MAPK activity. The findings also suggest that several ingredients of ABR such as Baicalien, Copistine, Epiberberine, Kaempferol, and Palmatine have good affinity with IL6, suggesting the promising potential of ABR in treating bone trauma, likely through IL6.

scholarly journals Network Pharmacology and Component Analysis Integrated Study to Unveil Molecular Mechanisms of A Traditional Chinese Medicine Decoction (Polygonum Multiflorum, Rehmannia Glutinosa, Senna Obtusifolia and Crataegus) in Hypertension Treatment

2020 ◽  
Author(s):  
Fui Fui Lem ◽  
Fernandes Opook ◽  
Fahcina P. Lawson ◽  
Thau Lym Wilson Yong ◽  
Fong Tyng Chee
Keyword(s):  
Mass Spectrometry ◽  
Molecular Mechanisms ◽  
Fluid Shear Stress ◽  
Quantitative Estimation ◽  
Renin Angiotensin System ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Rehmannia Glutinosa ◽  
Polygonum Multiflorum ◽  
Senna Obtusifolia

Abstract Background: Traditional Chinese Medicines (TCM) are known for their curative effects on hypertension through a holistic approach. The molecular mechanisms of the formulation comprising Polygonum multiflorum, Rehmannia glutinosa, Senna obtusifolia and Crataegus, used by Chinese practitioners in ameliorating hypertension, however remain a mystery. This initial study is thus aimed at unveiling the molecular mechanisms of this TCM formulation in treating hypertension. Methods: The methanolic extract compounds of the decoction were identified through Liquid chromatography mass spectrometry-mass spectrometry (LC-MS/MS). Oral bioavailability and drug likeness were then measured to filter out identified compounds. Several databases, such as the SwissTargetPrediction, STRING, OMIM and KEGG, were used to retrieve information on the predicted targets for the purpose of developing a network using Cytoscape Version 3.8. Enrichment analysis was then performed to elucidate the mechanisms of the decoction in hypertension mitigation. Results: A total of 11 compounds identified were revealed to possess bioavailable and drug like characteristics, based on the Veber and Quantitative Estimation of Drug-likeness (QED) parameters. Pathway analysis showed enrichment of pathways such as cardiac muscle contraction, fluid shear stress and atherosclerosis, dilated cardiomyopathy, renin-angiotensin system and hypertrophic cardiomyopathy (HCM), which are all strongly associated with hypertension. Conclusion: The network pharmacology analysis clearly shows that this TCM decoction ameliorates hypertension through several indirect pathways where most of the targets are involved in HCM, which is caused by hypertension.

scholarly journals Importance of Mitochondrial-Related Genes in Dilated Cardiomyopathy Based on Bioinformatics Analysis

2020 ◽  
Vol 5 (2) ◽  
pp. 117-129
Author(s):  
Yukuan Chen ◽  
Xiaohui Wu ◽  
Danchun Hu ◽  
Wei Wang
Keyword(s):  
Dilated Cardiomyopathy ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Enrichment Analysis ◽  
Microarray Dataset ◽  
Functional Enrichment ◽  
Cellular Respiration ◽  
Wide Range ◽  
Key Genes

We designed this study to identify potential key protein interaction networks, genes, and correlated pathways in dilated cardiomyopathy (DCM) via bioinformatics methods. We selected the GSE3586 microarray dataset, consisting of 15 dilated cardiomyopathic heart biopsy samples and 13 nonfailing heart biopsy samples. Initially, the GSE3586 dataset was downloaded and was analyzed with the limma package to identify differentially expressed genes (DEGs). A total of 172 DEGs consisting of 162 upregulated genes and ten downregulated genes in DCM were selected by the criterion of adjusted Pvalues less than 0.01 and the log2-fold change of 0.6 or greater. Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to view the biological processes, cellular components, molecular function, and KEGG pathways of the DEGs. Next, protein-protein interactions were constructed, and the hub protein modules were identified. Then we selected the key genes DLD, UQCRC2, DLAT, SUCLA2, ATP5A1, PRDX3, FH, SDHD, and NDUFV1, which are involved in a wide range of biological activities, such as the citrate cycle, oxidation-reduction processes and cellular respiration, and energy derivation by oxidation of organic compounds in mitochondria. Finally, we found that currently there are no related gene-targeting drugs after exploring the predicted interactions between key genes and drugs, and transcription factors. In conclusion, our study provides greater understanding of the pathogenesis and underlying molecular mechanisms in DCM. This contributes to the exploration of potential gene therapy targets.

scholarly journals Network Pharmacology Integrated Molecular Docking Reveals the Mechanism of Zhongfeng Xingnao Formula against Intracerebral Hemorrhage

2020 ◽  
Author(s):  
Can Wan ◽  
Ziyi Zhou ◽  
Yun Lu ◽  
Guangyao Zhang ◽  
Yefeng Cai ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Intracerebral Hemorrhage ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Underlying Mechanism ◽  
Network Pharmacology ◽  
Pathway Network ◽  
Drug Compound

Abstract Background: Previous studies have shown that Zhongfeng Xingnao Formula (ZXF) can effectively reduce the mortality of intracerebral hemorrhage (ICH), but the underlying mechanism of the treatment remained still unexplored. This study aimed to expound the potential mechanism of ZXF in the treatment of ICH through network pharmacology and molecular docking.Methods: The putative targets of ZXF were obtained from the TCMSP and Uniprot database, while the potential targets of ICH received from Drugbank, Genecards and OMIM database. Then through the Venn 2.1, the overlapping targets of disease and drug were gotten for the further study. The GO and KEGG enrichment analyses were performed by R version 4.0.2 software so that the signaling pathway was acquired to the subsequent analysis. Cytoscape was used to construct the drug-compound-target-pathway network and String was utilized for the protein-protein interaction network. What’s more, the interaction between compound and target was verified by the AutoDockTools and Autodock Vina. Results: There were a total of 166 ZXF-related targets and 1258 ICH-related targets obtained from the public databases. And 87 potential targets were both related to drug and disease. The GO enrichment analysis mainly involved receptor ligand activity, signaling receptor activator activity, and cytokine receptor binding, while the signaling pathway, such as Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, were significantly enriched in the KEGG enrichment analysis. The molecular docking elucidated that the aloe-emodin, beta-sitosterol, quercetin could bound well to the top five targets sorted by degree value.Conclusions: ZXF treated ICH through multiple compounds, multiple targets, and multiple pathways. The underlying mechanism of the treatment may be promoting angiogenesis, anti-inflammatory, anti-oxidative stress, and reversing atherosclerosis, which is of great significance for the treatment of ICH.

scholarly journals Decoding the Mechanism of Huanglian Jiedu Decoction in Treating Pneumonia Based on Network Pharmacology and Molecular Docking

2021 ◽  
Vol 9 ◽  
Author(s):  
Xianhai Li ◽  
Hua Tang ◽  
Qiang Tang ◽  
Wei Chen
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Clinical Symptoms ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Interleukin 17 ◽  
Active Ingredients ◽  
Hub Genes

Huang-Lian-Jie-Du decoction (HLJDD) has been used to treat pneumonia for thousands of years in China. However, our understanding of its mechanisms on treating pneumonia is still unclear. In the present work, network pharmacology was used to analyze the potential active ingredients and molecular mechanisms of HLJDD on treating pneumonia. A total of 102 active ingredients were identified from HLJDD, among which 54 were hit by the 69 targets associated with pneumonia. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we obtained the main pathways associated with pneumonia and those associated with the mechanism of HLJDD in the treatment of pneumonia. By constructing the protein–protein interaction network of common targets, 10 hub genes were identified, which were mainly involved in the tumor necrosis factor (TNF) signaling pathway, interleukin 17 (IL-17) signaling pathway, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Moreover, the results of molecular docking showed that the active ingredients of HLJDD had a good affinity with the hub genes. The final results indicate that HLJDD has a greater effect on bacterial pneumonia than on viral pneumonia. The therapeutic effect is mainly achieved by regulating the host immune inflammatory response and oxidative stress reaction, antibacterial microorganisms, alleviating the clinical symptoms of pneumonia, repairing damaged cells, and inhibiting cell migration.

scholarly journals Natural Xanthones and Skin Inflammatory Diseases: Multitargeting Mechanisms of Action and Potential Application

2020 ◽  
Vol 11 ◽  
Author(s):  
Natalie Vivien Gunter ◽  
Soek Sin Teh ◽  
Yang Mooi Lim ◽  
Siau Hui Mah
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Mapk Signaling ◽  
Mechanisms Of Action ◽  
Related Factor ◽  
Wide Range ◽  
Anti Inflammatory

The pathogenesis of skin inflammatory diseases such as atopic dermatitis, acne, psoriasis, and skin cancers generally involve the generation of oxidative stress and chronic inflammation. Exposure of the skin to external aggressors such as ultraviolet (UV) radiation and xenobiotics induces the generation of reactive oxygen species (ROS) which subsequently activates immune responses and causes immunological aberrations. Hence, antioxidant and anti-inflammatory agents were considered to be potential compounds to treat skin inflammatory diseases. A prime example of such compounds is xanthone (xanthene-9-one), a class of natural compounds that possess a wide range of biological activities including antioxidant, anti-inflammatory, antimicrobial, cytotoxic, and chemotherapeutic effects. Many studies reported various mechanisms of action by xanthones for the treatment of skin inflammatory diseases. These mechanisms of action commonly involve the modulation of various pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α), as well as anti-inflammatory cytokines such as IL-10. Other mechanisms of action include the regulation of NF-κB and MAPK signaling pathways, besides immune cell recruitment via modulation of chemokines, activation, and infiltration. Moreover, disease-specific activity contributed by xanthones, such as antibacterial action against Propionibacterium acnes and Staphylococcus epidermidis for acne treatment, and numerous cytotoxic mechanisms involving pro-apoptotic and anti-metastatic effects for skin cancer treatment have been extensively elucidated. Furthermore, xanthones have been reported to modulate pathways responsible for mediating oxidative stress and inflammation such as PPAR, nuclear factor erythroid 2-related factor and prostaglandin cascades. These pathways were also implicated in skin inflammatory diseases. Xanthones including the prenylated α-mangostin (2) and γ-mangostin (3), glucosylated mangiferin (4) and the caged xanthone gambogic acid (8) are potential lead compounds to be further developed into pharmaceutical agents for the treatment of skin inflammatory diseases. Future studies on the structure-activity relationships, molecular mechanisms, and applications of xanthones for the treatment of skin inflammatory diseases are thus highly recommended.

Pharmacologically potentials of different substituted coumarin derivatives

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Benzene Ring ◽  
Bioactive Compounds ◽  
Biological Activities ◽  
Pharmacological Properties ◽  
Coumarin Derivatives ◽  
Wide Range ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Coumarin Compounds

Coumarin and its derivatives are widely spread in nature. Coumarin goes to agroup as benzopyrones, which consists of a benzene ring connected to a pyronemoiety. Coumarins displayed a broad range of pharmacologically useful profile.Coumarins are considered as a promising group of bioactive compounds thatexhibited a wide range of biological activities like anti-microbial, anti-viral,antiparasitic, anti-helmintic, analgesic, anti-inflammatory, anti-diabetic, anticancer,anti-oxidant, anti-proliferative, anti-convulsant, and antihypertensiveactivities etc. The coumarin compounds have immense interest due to theirdiverse pharmacological properties. In particular, these biological activities makecoumarin compounds more attractive and testing as novel therapeuticcompounds.

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