scholarly journals Network Pharmacology Study Reveals the Mechanism of Astragali Radix in Treatment of Diabetic Nephropathy

2020 ◽  
Author(s):  
Chongmei Tian ◽  
Jing-bai Chen ◽  
Xiang Chen ◽  
Dao-zong Xia
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Therapeutic Effects ◽  
Disease Network ◽  
Astragali Radix ◽  
Target Disease

Abstract Background Diabetic nephropathy (DN), a unique complication of diabetes, could contribute to an increase in mortality. In this study, we predicted and proved the molecular pharmacological mechanism concerning the protective effects of Astragali Radix on DN. Methods The same potential target genes from Astragali Radix and DN were analyzed and constructed the protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment-related major targets and signal pathways were performed. The drug-ingredients-target-disease network was visually built using Cytoscape 3.6.1. The beneficial pharmacological activities of quercetin from Astragali Radix were confirmed by CCK-8 assay, determination of antioxidant parameters and Western blotting analysis. Results There are 12 bioactive components from Astragali Radix and 56 same targets between Astragali Radix and DN. The GO analysis results showed that the biological processes mainly included protein homodimerization activity. KEGG analysis indicate that the screened targets were most closely linked to the mitogen-activated protein kinase (MAPK) signaling pathway. The drug-ingredients-target-disease network results revealed that the therapeutic effects of Astragali Radix mainly included oxidative stress, inflammatory reaction and apoptosis. During the verification process, quercetin from Astragali Radix could attenuate cytotoxicity, enhance catalase (CAT) and superoxide dismutase (SOD) activities and suppress MAPK signaling pathway. Conclusions In the current study, network pharmacology with experimental analysis predicted and proved the therapeutic function of Astragali Radix by improving antioxidant capacity and suppressing MAPK signaling pathway, these investigations could provide a new perspective for further exploration of Astragali Radix on DN treatment.

Uncovering the Key miRNAs and Targets of the Liuwei Dihuang Pill in Diabetic Nephropathy-Related Osteoporosis based on Weighted Gene Co-Expression Network and Network Pharmacology Analysis

2021 ◽  
Vol 21 ◽  
Author(s):  
Ming Ming Liu ◽  
Nan Ning Lv ◽  
Rui Geng ◽  
Zhen Hua ◽  
Yong Ma ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Network Analysis ◽  
Signaling Pathway ◽  
Diabetic Complications ◽  
Cellular Response ◽  
Mapk Signaling ◽  
Functional Enrichment ◽  
Network Pharmacology ◽  
Integrated Analysis ◽  
Therapeutic Effects

Background: Diabetic nephropathy-related osteoporosis (DNOP) is the most common comorbid bone metabolic disorder associated with diabetes mellitus (DM). The Liuwei Dihuang Pill (LWD) is a traditional Chinese herbal medicine widely used to treat diabetic complications, including diabetic nephropathy (DN). This study aimed to identify the biomarkers of the mechanisms of DNOP in LWD with systems biology approaches. Methods: Herein, we performed an integrated analysis of the GSE51674 and GSE63446 datasets from the GEO database via weighted gene co-expression network and network pharmacology (WGCNA) analysis. In addition, a network pharmacology approach, including bioactive compounds, was used with oral bioavailability (OB) and drug-likeness (DL) evaluation. Next, target prediction, functional enrichment analysis, network analysis, and virtual docking were used to investigate the mechanisms of LWD in DNOP. Results : WGCNA successfully identified 63 DNOP-related miRNAs. Among them, miR-574 was significantly upregulated in DN and OP samples. A total of 117 targets of 22 components associated with LWD in DNOP were obtained. The cellular response to nitrogen compounds, the AGE-RAGE signaling pathway in diabetic complications, and the MAPK signaling pathway were related to the main targets. Network analysis showed that kaempferol and quercetin were the most significant components. MAPK1 was identified as a potential target of miR-574 and the hub genes in the protein-protein interaction (PPI) network. The docking models demonstrated that kaempferol and quercetin had a strong binding affinity for Asp 167 of MAPK1. Conclusion: This study demonstrated that miR-574 may play important roles in DNOP, and the therapeutic effects of kaempferol and quercetin on LWD in DNOP might be mediated by miR-574 by targeting MAPK1. Our results provide new perspectives for further studies on the anti-DNOP mechanism of LWD.

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 A Network Pharmacology-Based Approach for Exploring Key Active Compounds and Pharmacological Mechanisms of Tangshen Formula for Treatment of Diabetic Nephropathy

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Weie Zhou ◽  
Xuefeng Zhou ◽  
Yuan Zhang ◽  
Yuyang Wang ◽  
Wenjie Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Synergistic Effects ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Promising Source ◽  
Tangshen Formula ◽  
Compound Target

Diabetic nephropathy (DN) is one of the common and severe microvascular complications of diabetes mellitus (DM). The occurrence and development of DN are related to multiple factors in the human body, which makes DN a complex disease, and the pathogeneses of DN have not yet been fully illustrated. Furthermore, DN lacks effective drugs for treatment nowadays. Chinese herbal medicine (CHM) often shows the feature of multicomponents, multitargets, multipathways, and synergistic effects and shows a promising source of new therapeutic drugs for DN. As a CHM, Tangshen Formula (TSF) was used to treat DN patients in China. However, its bioactive compounds and holistic pharmacological mechanisms on DN are both unclear. A network pharmacology approach was firstly applied to explore multiple active compounds and multiple key pharmacological mechanisms for TSF treating DN by drug-targeted interaction databases, herb-compound-target network, protein-protein interaction network, compound-target-pathway network, and analysis methods. And the results showed that TSF have the characteristic of multicomponents, multitargets, multipathways, and synergistic effects for treating DN. The quercetin, naringenin, kaempferol, and isorhamnetin as key active compounds and the PI3K-Akt signaling pathway, TNF signaling pathway, nonalcoholic fatty liver disease (NAFLD), focal adhesion, rap1 signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, and insulin resistance as the key molecular mechanisms play important roles in TSF treating DN. Moreover, quercetin, naringenin, kaempferol, and isorhamnetin were successfully detected in TSF by the UHPLC-MS/MS analysis method. And their concentrations were 0.224, 8.295, 0.0564, and 0.0879 mg·kg-1, respectively. The present findings not only provide new insights for a deeper understanding of the constituent basis and pharmacology of TSF but also provide guidance for further pharmacological studies on TSF.

scholarly journals Combined Effect of Deoxynivalenol (DON) and Porcine Circovirus Type 2 (Pcv2) on Inflammatory Cytokine mRNA Expression

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 422
Author(s):  
Chao Gu ◽  
Xiuge Gao ◽  
Dawei Guo ◽  
Jiacai Wang ◽  
Qinghua Wu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Porcine Circovirus Type ◽  
Mapk Signaling ◽  
Porcine Circovirus Type 2 ◽  
Mapk Signaling Pathway ◽  
Porcine Circovirus ◽  
Signal Pathways ◽  
Dependent Manner

A host’s immune system can be invaded by mycotoxin deoxynivalenol (DON) poisoning and porcine circovirus type 2 (PCV2) infections, which affect the host’s natural immune function. Pro-inflammatory cytokines, IL-1β and IL-6, are important regulators in the process of natural immune response, which participate in inflammatory response and enhance immune-mediated tissue damage. Preliminary studies have shown that DON promotes PCV2 infection by activating the MAPK signaling pathway. Here, we explored whether the mRNA expression of IL-1β and IL-6, induced by the combination of DON and PCV2, would depend on the MAPK signaling pathway. Specific pharmacological antagonists U0126, SP600125 and SB203580, were used to inhibit the activities of ERK, JNK and p38 in the MAPK signaling pathway, respectively. Then, the mRNA expression of IL-1β and IL-6 in PK-15 cells was detected to explore the effect of the MAPK signaling pathway on IL-1β and IL-6 mRNA induced by DON and PCV2. The results showed that PK-15 cells treated with DON or PCV2 induced the mRNA expression of IL-1β and IL-6 in a time- and dose-dependent manner. The combination of DON and PCV2 has an additive effect on inducing the mRNA expression of IL-1β and IL-6. Additionally, both DON and PCV2 could induce the mRNA expression of IL-1β and IL-6 via the ERK and the p38 MAPK signal pathways, while PCV2 could induce it via the JNK signal pathway. Taken together, our results suggest that MAPKs play a contributory role in IL-1β and IL-6 mRNA expression when induced by both DON and PCV2.

scholarly journals Huanglian Jiedu Decoction Exerts Antipyretic Effect by Inhibiting MAPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xing Li ◽  
Shizhang Wei ◽  
Xiao Ma ◽  
Haotian Li ◽  
Manyi Jing ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Western Blotting ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Potential Mechanism ◽  
Model Group ◽  
Rat Serum ◽  
Antipyretic Effect ◽  
Tnf Α

Aim. The aim of this study was to explore the antipyretic effect and potential mechanism of Huanglian Jiedu Decoction (HLJDD) on LPS-induced fever in rats. Materials and Methods. The fever rat model was established by LPS. Anal temperature of rats was measured every 1 hour after modeling. TNF-α, IL-6, PGE2, and cAMP in rat serum or hypothalamus tissue were detected by ELISA kit. In order to explore the potential active ingredients and mechanism of antipyretic effect of HLJDD, we predicted the underlying antipyretic mechanism by using network pharmacology and then verified its mechanism by Western Blotting. Results. The results showed that HLJDD can alleviate LPS-induced fever in rats. The expression levels of TNF-α, IL-6, PGE2, and cAMP in the treatment group were significantly lower than those in the model group. Western Blotting results showed that the protein expression of p-ERK, p-JNK, and p-P38 was significantly inhibited. Conclusion. The findings suggest that HLJDD has a good antipyretic effect on LPS-induced fever in rats, which may be closely related to the inhibition of MAPK signaling pathway.

scholarly journals A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of Atherosclerosis

2021 ◽  
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Chronic Inflammatory Disease ◽  
Mapk Signaling Pathway ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Overlapping Genes

Abstract Background: Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its critical bioactive compounds and their mechanisms against AS have not been unveiled. This research aimed to identify the key compounds(s) and mechanism(s) of GL against AS through network pharmacology.Methods: The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the gene(s) associated with the screened compound(s) or AS related genes were identified by public databases, and we selected the overlapping genes using a Venn diagram. The networks between overlapping genes and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed molecular docking test (MDT) to identify key gene(s), compound(s) on AutoDockVina.Results: A total of 35 compounds in GL was detected via GC-MS, and 34 compounds (accepted by the Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 genes and 2,606 AS-related genes were identified by DisGeNET and Online Mendelian Inheritance in Man (OMIM). The final 98 overlapping genes were extracted between the compounds-genes network and AS-related genes. On Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the number of 27 signaling pathways were sorted out, and a hub signaling pathway (MAPK signaling pathway), a core gene (PRKCA), and a key compound (Benzamide, 4-acetyl-N-(2,6-dimethylphenyl)) were selected among the 27 signaling pathways via MDT. Conclusion: Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway.

Exploring the Potential Mechanism of Shufeng Jiedu Capsule for Treating COVID-19 by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation

2020 ◽  
Vol 23 ◽  
Author(s):  
Zhenjie Zhuang ◽  
Xiaoying Zhong ◽  
Huanhuan Zhang ◽  
Huiqi Chen ◽  
Boxiang Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Holistic View ◽  
Chinese Patent ◽  
Molecule Docking

Objective: Shufeng Jiedu capsule (SFJDC) is a well-known Chinese patent drug that is recommended as a basic prescription and applied widely in the clinical treatment of COVID-19. However, the exact molecular mechanism of SFJDC remains unclear. The present study aims to determine the potential pharmacological mechanisms of SFJDC in the treatment of COVID-19 based on network pharmacology. Methods: The network pharmacology-based strategy includes collection and analysis of active compounds and target genes, network construction, identification of key compounds and hub target genes, KEGG and GO enrichment, recognition and analysis of main modules, as well as molecule docking. Results: A total of 214 active chemical compounds and 339 target genes of SFJDC were collected. Of note, 5 key compounds ( β -sitosterol, luteolin, kaempferol, quercetin, and stigmasterol) and 10 hub target genes (TP53, AKT1, NCOA1, EGFR, PRKCA, ANXA1, CTNNB1, NCOA2, RELA and FOS) were identified based on network analysis. The hub target genes mainly enriched in pathways including MAPK signaling pathway, PI3K-Akt signaling pathway and cAMP signaling pathway, which could be the underlying pharmacological mechanisms of SFJDC for treating COVID-19. Moreover, the key compounds had high binding activity with three typical target genes. Conclusions: y network pharmacology analysis, SFJDC was found to effectively improve immune function and reduce inflammatory responses based on its key compounds, hub target genes, and the relevant pathways. These findings may provide valuable evidence for explaining how SFJDC exerting the therapeutic effects on COVID-19, providing a holistic view for further clinical application.

scholarly journals The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Li Peng ◽  
Jie Li ◽  
Yixing Xu ◽  
Yangtian Wang ◽  
Hong Du ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
Diabetic Rats ◽  
Mapk Signaling Pathway ◽  
Pathological Changes ◽  
Diabetic Kidney ◽  
Beraprost Sodium

Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats.Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group. At the end of the 8-week experiment, we measured renal pathological changes and the activation of the p38 MAPK signaling pathway and inflammation.Result. After BPS treatment, renal function, 24-hour urine protein, lipid profiles, and blood glucose level were improved significantly; meanwhile, inflammation and the expression of p38 MAPK signaling pathway in the diabetic kidney were attenuated.Conclusions. BPS significantly prevented type 2 diabetes induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms are complicated but may be mainly attributed to the inhibition of the p38 MAPK signaling pathway and inflammation in the diabetic kidney.

Study on the Mechanism of Bushen Jianpi Decoction in the Treatment of T2DM Based on Network Pharmacology

2021 ◽  
Author(s):  
Dongqiang Luo ◽  
Ying Shao ◽  
Yong Sun ◽  
Shuntang Du ◽  
Feng Liu
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Target Genes ◽  
Fluid Shear Stress ◽  
Interaction Network ◽  
Binding Potential ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Protein Protein Interaction ◽  
Target Disease

Abstract Through the preliminary clinical observation, we had found that Bushen Jianpi decoction (BJD) combined with had better efficacy and less side effects, but its mechanism was not clear. The purpose of this study was to determine its molecular targets and mechanism in T2DM therapy by means of network pharmacology and molecular docking.Results: A total of 144 candidate compounds and 1103 differentially expressed genes were screened, and 43 common targets related to T2DM in BJD were identified. The "TCM-compound-target-disease" network suggested that quercetin, luteolin and kaempferol were the top three compounds. Through protein-protein interaction network, 45 core target genes were identified, including ITGA4, TP53, MYC and so on. GO enrichment showed that genes were significantly enriched in biological processes such as response to oxidative stress, response to lipopolysaccharide, response to molecule of bacterial origin and response to reactive oxygen species. KEGG enrichment showed that there was significant gene enrichment in Fluid shear stress and atherosclerosis, TNF signaling pathway, P13K-Akt signaling pathway, IL-17 signaling pathway and AGE-RAGE signaling pathway in diabetic complications signal pathways. The results of molecular docking showed that the key components of BJD had good binding potential with target genes. Conclusions: BJD may play a role in the treatment of T2DM through anti-inflammation, antioxidation and regulating metabolism, but it still needs to be further confirmed by experiments.Keywords: Network pharmacology, GEO database, Molecular docking, Bushen Jianpi decoction; T2DM

scholarly journals To explore the material basis and mechanism of Lianhua Qingwen Prescription against COVID-19 based on network pharmacology

2020 ◽  
Vol 1 ◽  
pp. 3
Author(s):  
Wenpan Peng ◽  
Di Han ◽  
Yong Xu ◽  
Fanchao Feng ◽  
Zhichao Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
T Cell Activation ◽  
Mechanism Of Action ◽  
Cell Activation ◽  
Chemical Constituents ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Material Basis

Objective: In the treatment of COVID-19, the application of Lianhua Qingwen Prescription has become growingly widespread, however, the mechanism of action is still unclear. To explore the material basis and mechanism of Lianhua Qingwen Prescription against SARS-CoV-2, to provide a reference for the treatment of COVID-19. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SwissTargetPrediction, and Similarity Ensemble Approach (SEA) database were used to search the chemical constituents and targets of Lianhua Qingwen Prescription. The targets of COVID-19 were screened by GeneCards, Therapeutic Target Database (TTD), and Comparative Toxicogenomics Database (CTD). Cytoscape software was used to construct a “drug-component-target” network diagram and the mechanism of action was predicted by enrichment analysis. Results: Two hundred and twenty four active components, 246 drug therapeutic targets, and 16,611 potential targets of Lianhua Qingwen Prescription were mined out. Moreover, 163 common targets were obtained, including PTGS2, IL6, CASP3, mapk1, EGFR, ACE2, etc. Thirty seven items were obtained by Gene Ontology (GO) enrichment analysis, mainly involving T-cell activation, virus receptor, and inflammatory reaction, etc. One hundred and forty items were obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enriched analysis, including TNF signaling pathway, MAPK signaling pathway, and IL-17 signaling pathway. Conclusion: Compounds such as quercetin and kaempferol play an important role in anti-COVID-19 through the TNF signaling pathway and MAPK signaling pathway.

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