scholarly journals Systems-Pharmacology-Based Identification of Antitumor Necrosis Factor Effect in Mimeng Flower Decoction for the Treatment of Diabetic Retinopathy

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Yingzi Li ◽  
Ying Huang ◽  
Changsen Tu
Keyword(s):  
Diabetic Retinopathy ◽  
Binding Affinity ◽  
Diabetic Rat ◽  
Systems Pharmacology ◽  
Disease Network ◽  
Active Compounds ◽  
Hub Gene ◽  
Target Disease ◽  
Necrosis Factor ◽  
Compound Target

The traditional Chinese medicine of Mimeng flower decoction (MFD) is effective in treating diabetic retinopathy (DR), but the mechanism is still unclear. This study aims at investigating the mechanism of MFD in treating DR. First, active compounds in MFD were filtered out by the systems pharmacology method and used as bait to fish potential targets. The common genes between the targets and DR-related genes were selected to construct the compound-target-disease network and identify the network hub gene as a key gene. Molecular docking was simulated to assess the binding affinity of active compounds towards the gene protein. Streptozotocin- (STZ-) induced diabetic rat model was administered to evaluate the efficacy of MFD in treating DR and its effects on retinal gene expression. Finally, 53 active compounds were screened out from the seven herbs in MFD, with a total of 136 targets. After intersecting with 210 DR-related genes, 21 common genes were applied to construct the network, and tumor necrosis factor (TNF) was identified as the hub gene. The active compounds of acacetin, kaempferol, luteolin, and quercetin showed a good binding affinity towards TNF (C-score ≥ 4). In diabetic rats, MFD treatment reversed the retinal impairment and decreased retinal TNF expression significantly. In conclusion, this study adopted the method of systems pharmacology to screen out active compounds and construct the compound-target-disease network and found that MFD could ameliorate DR by downregulating the network hub gene of TNF.

scholarly journals Identification of Key Pathways and Targets of Kai Xin San in The Treatment of Alzheimer's Disease Based On a Network Pharmacology Approach and Experimental Validation

2021 ◽  
Author(s):  
Rong Yang ◽  
Kan Wang ◽  
Tuo Li ◽  
Mianmian Liao ◽  
Mingwang Kong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Binding Affinity ◽  
Venn Diagram ◽  
Disease Network ◽  
Target Proteins ◽  
Target Disease ◽  
Compound Target

Abstract Background: Alzheimer's disease (AD) is the commonest neurodegenerative disease characterized with a progressive loss of cognitive functions and memory decline. Kai Xin San (KXS), a traditional Chinese herbal classic prescription, has been used to ameliorate cognitive dysfunction for thousands of years. However, its specific pharmacological molecular mechanisms have not been fully clarified.Methods: The ingredients of KXS and their corresponding targets were firstly screened from ETCM database. AD-related target proteins were obtained from Malacards database and DisGeNet database. Venn diagram was used to intersect the common targets between KXS and AD. Then, key ingredients and key targets were identified from compound-target-disease network and protein-protein interaction (PPI) network analysis respectively. Moreover, the binding affinity between the key ingredients and targets were verified by molecular docking. KEGG enrichment analysis further predicted the potential key signaling pathway involved in the treatment of KXS on AD, and the predicted signaling pathway was validated via experimental approach.Results: A total of 38 ingredients and 469 corresponding targets were screened, and 264 target proteins associated with AD were obtained. Compound-target-disease network and PPI identified the key active ingredients and targets, which correlate with the treatment of KXS on AD. Molecular docking revealed a good binding affinity between key ingredients and targets. KEGG pathway analysis suggested the potential effect of KXS in treatment of AD via Aβ-GSK3β-Tau pathway. Aβ1-42-injected induced a decline in spatial learning and memory and upregulated the expression of GSK3β and CDK5 along with the downregulated PP1 and PP2 expression. However, KXS significantly improve the cognitive deficits induced by Aβ1-42, decrease the GSK3β and CDK5 levels and increase the expression of PP1 and PP2.Conclusions: Our research elucidated that KXS exerted neuroprotective effects through regulating the Aβ-GSK3β-Tau signaling pathway, which provided a novel insight into the therapeutic mechanism of KXS in treatment of AD.

scholarly journals Study on the Mechanism of Lianpu Drink for the Treatment of Chronic Gastritis Based on Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shuhan Zhou ◽  
Yanjun Duan ◽  
Yu Deng ◽  
Miao Wang ◽  
Chaoqun Huang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Chronic Gastritis ◽  
Mechanisms Of Action ◽  
Network Pharmacology ◽  
Biological Pathway ◽  
Disease Network ◽  
Target Disease ◽  
Compound Target

Chronic gastritis (CG) places a considerable burden on the healthcare system worldwide. Traditional Chinese Medicine (TCM) formulas characterized by multicompounds and multitargets have been acknowledged with striking effects in the treatment of CG in China’s history. Nevertheless, their accurate mechanisms of action are still ambiguous. In this study, we analyzed the effective compounds, potential targets, and related biological pathway of Lianpu Drink (LPD), a TCM formula which has been reported to have a therapeutic effect on CG, by contrasting a “compound-target-disease” network. According to the results, 92 compounds and 5762 putative targets of LPD were screened; among them, 8 compounds derived from different herbs in LPD and 30 common targets related to LPD and CG were selected as candidate compounds and precision targets, respectively. Meanwhile, the predicted common targets were verified by Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis and pharmacological experiments. The results demonstrated that quercetin, ephedrine, trigonelline, crocetin, and β-sitosterol were major effective compounds of LPD responsible for the CG treatment by inhibiting the activation of the JAK 2-STAT 3 signaling pathway to reduce the expressions of cyclin D1 and Bcl-2 proteins. The study provides evidence for the mechanism of understanding of LPD for the treatment of CG.

scholarly journals Network Pharmacology-Based Investigation into the Mechanisms of Quyushengxin Formula for the Treatment of Ulcerative Colitis

2019 ◽  
Vol 2019 ◽  
pp. 1-22
Author(s):  
Haojie Yang ◽  
Ying Li ◽  
Sichen Shen ◽  
Dan Gan ◽  
Changpeng Han ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Bioactive Compounds ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Disease Network ◽  
Pathway Network ◽  
Similarity Algorithm ◽  
Target Network ◽  
Target Disease ◽  
Compound Target

Objective. Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease whose treatment strategies remain unsatisfactory. This study aims to investigate the mechanisms of Quyushengxin formula acting on UC based on network pharmacology. Methods. Ingredients of the main herbs in Quyushengxin formula were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Absorption, distribution, metabolism, and excretion properties of all ingredients were evaluated for screening out candidate bioactive compounds in Quyushengxin formula. Weighted ensemble similarity algorithm was applied for predicting direct targets of bioactive ingredients. Functional enrichment analyses were performed for the targets. In addition, compound-target network, target-disease network, and target-pathway network were established via Cytoscape 3.6.0 software. Results. A total of 41 bioactive compounds in Quyushengxin formula were selected out from the TCMSP database. These bioactive compounds were predicted to target 94 potential proteins by weighted ensemble similarity algorithm. Functional analysis suggested these targets were closely related with inflammatory- and immune-related biological progresses. Furthermore, the results of compound-target network, target-disease network, and target-pathway network indicated that the therapeutic effects of Quyushengxin on UC may be achieved through the synergistic and additive effects. Conclusion. Quyushengxin may act on immune and inflammation-related targets to suppress UC progression in a synergistic and additive manner.

scholarly journals Exploring the Potential Mechanism of Chuanxiong Rhizoma Treatment for Migraine Based on Systems Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xianhua Wen ◽  
Yuncheng Gu ◽  
Beili Chen ◽  
Feipeng Gong ◽  
Wenting Wu ◽  
...  
Keyword(s):  
Drug Targets ◽  
Treatment Process ◽  
Kegg Pathway ◽  
Systems Pharmacology ◽  
Active Compounds ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Target Disease ◽  
Tcm Theory ◽  
Drug Compound

Migraine is a disease whose aetiology and mechanism are not yet clear. Chuanxiong Rhizoma (CR) is employed in traditional Chinese medicine (TCM) to treat various disorders. CR is effective for migraine, but its active compounds, drug targets, and exact molecular mechanism remain unclear. In this study, we used the method of systems pharmacology to address the above issues. We first established the drug-compound-target-disease (D-C-T-D) network and protein-protein interaction (PPI) network related to the treatment of migraine with CR and then established gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results suggest that the treatment process may be related to the regulation of inflammation and neural activity. The docking results also revealed that PTGS2 and TRPV1 could directly bind to the active compounds that could regulate them. In addition, we found that CR affected 11 targets that were more highly expressed in the liver or heart but were the lowest in the whole brain. It also expounds the description of CR channel tropism in TCM theory from these angles. These findings not only indicate that CR can be developed as a potential effective drug for the treatment of migraine but also demonstrate the application of systems pharmacology in the discovery of herbal-based disease therapies.

scholarly journals Systems Pharmacology–Based Dissection of Anti-Cancer Mechanism of Traditional Chinese Herb Saussurea involucrata

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Lanyu He ◽  
Qingqing Jiang ◽  
Hongqing Zhu ◽  
Dehua Kong ◽  
...  
Keyword(s):  
Kegg Pathway ◽  
Chinese Herb ◽  
Pathway Enrichment Analysis ◽  
No Production ◽  
Systems Pharmacology ◽  
Active Compounds ◽  
Saussurea Involucrata ◽  
Pathway Enrichment ◽  
Anti Cancer ◽  
Target Disease

Cancer has the highest mortality in humans worldwide, and the development of effective drugs remains a key issue. Traditional Chinese medicine Saussurea involucrata (SI) exhibits a series of effects, such as anti-cancer, but the action mechanisms are still unclear. Here, systems pharmacology was applied to reveal its anti-cancer mechanism. First, we screened the active compounds of SI. Then, the compound–target network, target–disease network, and target–pathway network were constructed. DAVID was applied for GOBP analysis and KEGG pathway enrichment analysis on cancer-related targets. Seven potential compounds and 187 targets were identified. The target–disease classification network showed that compounds mainly regulated proteins related to cancer, nervous system diseases, and cardiovascular system diseases. Also, SI anti-tumor effect mainly associated with the regulation of NO production, angiogenesis, MAPK, and PKB from GOBP enrichment. Additionally, KEGG pathway enrichment indicated that targets involved in anti-inflammatory action, inhibiting angiogenesis and anti-proliferation or inducing apoptosis. Experimental validation showed that four active compounds could inhibit cell proliferation and promote apoptosis in A549 (except for kaempferol), PC-3, and C6 cells. This study not only provides experimental evidence for further research on SI in cancer treatment but also promotes the development of potential drugs of SI in modern medicine.

scholarly journals Association of tumor necrosis factor-alpha -308 G/A and -238 G/A polymorphism with diabetic retinopathy: a systematic review and updated meta-analysis.

2020 ◽  
Author(s):  
Wenna Gao ◽  
Ruilin Zhu ◽  
liu yang
Keyword(s):  
Diabetic Retinopathy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Meta Analysis ◽  
Entire Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background: Mounting evidence has suggested tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR [the OR(95%CI) of (GA versus GG), (GA + AA) versus GG, and (A versus G) are 1.21(1.04, 1.41), 1.20(1.03, 1.39), and 1.14(1.01, 1.30), respectively]. And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was mild correlation in the entire group [the OR(95%CI) of (GA versus GG) is 1.55(1.14,2.11) ], which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.

scholarly journals A Network Pharmacology-Based Study on Pharmacological Activities and Mechanisms of Essential Oil in Leaves of C. Grandis ‘Tomentosa’

2021 ◽  
Author(s):  
Jieshu You ◽  
Sheng-cai He ◽  
Liang Chen ◽  
Zhen-hui Guo ◽  
Fei Gao ◽  
...  
Keyword(s):  
Essential Oil ◽  
Function Analysis ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Pathway Enrichment Analysis ◽  
Health Food ◽  
Disease Network ◽  
Pharmacological Activities ◽  
Integrated Network ◽  
Target Disease

Abstract Background and Objective: Citrus grandis ‘Tomentosa’, as the fruit epicarp of C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck, is widely used in health food and medicine. Actually, based on our survey results, there are also rich essential oils with bioativities in leaves, but the chemical compounds in this part and relevant pharmacological activities have never been studied systematically yet. Therefore, this study was to preliminarily decipher the pharmacological activities and mechanisms of the essential oil in leaves of C. grandis ‘Tomentosa’ by an integrated network pharmacology approach. Methods: Essential oil compositions from leaves of C. grandis ‘Tomentosa’ were identified using GC-MS/MS. And then the targets of these oil compositions were predicted and screened from TCMSP, SwissTargetPrediction, STITCH and SEA databases. STRING database was used to construct the protein-protein interaction networks, and the eligible protein targets were input into WebGestalt 2019 to carry out GO enrichment and KEGG pathway enrichment analysis. Based on the potential targets, disease enrichment information was obtained by TTD databases. Cytoscape software was used to construct the component-target-disease network diagrams. Results: Finally, 61 essential oil chemical components were identified by GC-MS/MS, which correspond to 679 potential targets. Biological function analysis showed that there were 12, 19, and 12 GO entries related to biological processes, cell components and molecular functions, respectively. 43 KEGG pathways were identified, of which the most significant categories were terpenoid backbone biosynthesis, TNF signaling pathway and leishmaniasis. The component-target-disease network diagram revealed that the essential oil compositions in leaves of C. grandis ‘Tomentosa’ could treat tumors, immune diseases, neurodegenerative diseases and respiratory diseases, which were highly related to CHRM1, PTGS2, CASP3, MAP2K1 and CDC25B.Conclusion: This study may provide a new insight into C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck and may provide useful information for future utilization and development.

scholarly journals Identifying Active Compounds and Targets of Fritillariae thunbergii against Influenza-Associated Inflammation by Network Pharmacology Analysis and Molecular Docking

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3853 ◽  
Author(s):  
Minjee Kim ◽  
Ki Hoon Park ◽  
Young Bong Kim
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Target Genes ◽  
Inflammatory Diseases ◽  
Network Pharmacology ◽  
Pharmacokinetic Parameters ◽  
Active Compounds ◽  
Biological Targets ◽  
Underlying Mechanisms ◽  
Cox 1

Complications due to influenza are often associated with inflammation with excessive release of cytokines. The bulbs of Fritillariae thunbergii (FT) have been traditionally used to control airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate active compounds, the targets, and underlying mechanisms of FT for the treatment of influenza-induced inflammation, systems biology was employed. Active compounds of FT were identified through the TCMSP database according to oral bioavailability (OB) and drug-likeness (DL) criteria. Other pharmacokinetic parameters, Caco-2 permeability (Caco-2), and drug half-life (HL) were also identified. Biological targets of FT were retrieved from DrugBank and STITCH databases, and target genes associated with influenza, lung, and spleen inflammation were collected from DisGeNET and NCBI databases. Compound-disease-target (C-D-T) networks were constructed and merged using Cytoscape. Target genes retrieved from the C-D-T network were further analyzed with GO enrichment and KEGG pathway analysis. In our network, GO and KEGG results yielded two compounds (beta-sitosterol (BS) and pelargonidin (PG)), targets (PTGS1 (COX-1) and PTGS2 (COX-2)), and pathways (nitric oxide, TNF) were involved in the inhibitory effects of FT on influenza-associated inflammation. We retrieved the binding affinity of each ligand-target, and found that PG and COX-1 showed the strongest binding affinity among four binding results using a molecular docking method. We identified the potential compounds and targets of FT against influenza and suggest that FT is an immunomodulatory therapy for influenza-associated inflammation.

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