Based on Network Pharmacology and Molecular Docking to Explore the Underlying Mechanism of Huangqi Gegen Decoction for Treating Diabetic Nephropathy

Ding, Shanshan; Wang, Weihao; Song, Xujiao; Ma, Hao

doi:10.1155/2021/9928282

Cited by 13 publications

(8 citation statements)

References 40 publications

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“…A pharmaceutical experiment also proves that metformin increases the production of VEGFA in podocytes to reduce proteinuria through hypoxia-inducible factor-2 α -VEGFA signaling pathway [ 21 ]. And a network pharmacology research shows that Huangqi Gegen decoction whose clinical efficacy has been widely confirmed [ 22 ] can bind with VEGFA to play the role of anti-inflammatory, antiapoptosis, antioxidation, and autophagy effects to improve renal function, thus delaying the development of DN [ 23 ]. All of these researches prove that VEGFA is beneficial to the establishment and maintenance of glomerular structure and function and provide a novel molecular mechanism for protecting renal function.…”

Section: Discussionmentioning

confidence: 99%

Integrated Bioinformatics and Clinical Correlation Analysis of Key Genes, Pathways, and Potential Therapeutic Agents Related to Diabetic Nephropathy

Chen

Jiang

2022

Disease Markers

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Background. Diabetic nephropathy (DN) is a common microvascular complication of diabetes and a major cause of end-stage renal disease, resulting in a substantial socioeconomic burden around the world. Some unknown biomarkers, mechanisms, and potential novel agents regarding DN are yet to be identified. Methods. GSE30528 and GSE1009 were downloaded as training datasets to identify differentially expressed genes (DEGs) of DN. Common DEGs were selected for further analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEGs were performed to explore molecular mechanisms and pathways. Protein-protein interaction (PPI) network of DEGs was used to identify the top 10 hub genes of DN. Expression profiles of the hub genes were validated in GSE96804 and GSE47183 datasets. The clinical correlation analyses were conducted to confirm the association between key genes and clinical characteristics in the Nephroseq v5 database. The Drug Gene Interaction Database was used to predict potential targeted drugs. Results. 345 and 1228 DEGs were identified in GSE30528 and GSE1009, respectively; and 120 common DEGs were found. The biological process of DEGs was significantly enriched in kidney development. PI3K-Akt signaling pathway, focal adhesion, complement and coagulation cascades were significantly enriched KEGG pathways. The identified top10 hub genes were VEGFA, NPHS1, WT1, TJP1, CTGF, FYN, SYNPO, PODXL, TNNT2, and BMP2. VEGFA, NPHS1, WT1, CTGF, SYNPO, PODXL, and TNNT2 were significantly downregulated in DN. VEGFA, NPHS1, WT1, CTGF, SYNPO, and PODXL were positively correlated with glomerular filtration rate. The targeted drugs or molecular compounds were enalapril, sildenafil, and fenofibrate target for VEGFA; losartan target for NPHS1; halofuginone, deferoxamine, curcumin, and sirolimus target for WT1; and purpurogallin target for TNNT2. Conclusions. VEGFA, NPHS1, WT1, CTGF, SYNPO, and PODXL are promising biomarkers for diagnosing and evaluating the progression of DN. The drug-gene interaction analyses provide a list of candidate drugs for the precise treatment of DN.

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Section: Discussionmentioning

confidence: 99%

Integrated Bioinformatics and Clinical Correlation Analysis of Key Genes, Pathways, and Potential Therapeutic Agents Related to Diabetic Nephropathy

Chen

Jiang

2022

Disease Markers

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“…[11] Oral bioavailability ≥ 30% and drug-likeness ≥ 0.18 were used as the criteria to screen the active ingredients. [12] Then, the related targets of active ingredients of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database. The Swiss Target Prediction database (www.swisstargetprediction.ch) was used to supplement the ingredients with missing targets, and obtained the targets with the top probability values.…”

Section: Methodsmentioning

confidence: 99%

Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation

Deng

Luo

et al. 2023

Medicine

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This study aimed to explore the possible mechanisms of Ling Gui Zhu Gan decoction (LGZGD) in the treatment of nephrotic syndrome (NS) using network pharmacology combined with molecular docking and molecular dynamics simulation. The active ingredients of LGZGD and their targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Swiss Target Prediction database. The NS targets were retrieved from Genecards, OMIM and Drugbank databases. Next, the intersecting targets of drug and disease were imported into the String database for protein-protein interaction network analysis, and the core targets were identified through topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed in the Metascape platform. Finally, molecular docking and molecular dynamics simulation were performed for further validation. The network analysis showed that 109 active ingredients of LGZGD were associated with 105 targets in NS. The key active ingredients (quercetin, kaempferol, naringenin, licochalcone A, formononetin, beta-sitosterol) and the core targets (IL6, AKT1, TNF, VEGFA, TP53, JUN, IL1B, CASP3, EGFR, and STAT3) were further identified. Enrichment analysis indicated that multiple biological processes and pathways, including AGE-RAGE, PI3K-Akt, JAK-STAT, and HIF-1 signaling pathways, might be regulated by LGZGD in the treatment of NS. Molecular docking and molecular dynamics simulation results further indicated that the key active ingredients of LGZGD could stably bind to the core targets through hydrogen bonding and hydrophobic interaction. This study demonstrates that the active ingredients of LGZGD may regulate multiple targets, biological processes and signaling pathways in NS. Our findings may provide a theoretical basis for further studies on LGZGD in the treatment of NS.

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“…[1,17] The corresponding drugs were then searched in the Genecards database, and protein targets were collected. [14]…”

Section: Selection Of Standard Drugs For Acne and Collection Of Relat...mentioning

confidence: 99%

Exploring the mechanism of action of Hedyotis diffusa Willd on acne using network analysis

Seo

Kim

2023

Medicine

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In this study, we used a network pharmacological method to explore the active ingredients of Hedyotis diffusa Willd (HDW) in the treatment of acne and elucidated the physiological mechanisms in the human body in which they are involved. We identified the active compounds of HDW that are expected to act effectively in the human body using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform and extracted potential interacting proteins for each active compound using the Swiss Target Prediction platform. Next, we analyzed the potential mechanisms of action of the protein targets shared by HDW and each standard drug on acne and assessed the possibility of spontaneous occurrence of the binding between proteins and active compounds through the molecular docking process. Seven active compounds were selected according to the oral bioavailability and drug-likeness criteria of the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. Subsequently, 300 protein targets were collected from the Swiss Target Prediction. Using the Search Tool for the Retrieval of Interacting Genes/Proteins database, a protein-protein interaction network was constructed by analyzing the relationship between HDW, acne, and each standard drug. By analyzing the gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway, the "positive regulation of lipid metabolic process" was found to be the most involved pathway shared by HDW, acne, and isotretinoin. An analysis of the protein targets shared by the antibiotic agents with HDW and acne found that "cholesterol storage" in tetracycline, "icosacoid transport" in azithromycin, "steroid hydroxylase activity" in erythromycin, "positive regulation of leukocyte tethering or rolling" in clindamycin, "response to UV-A" in minocycline, "steroid 11-beta-monooxygenase activity" in doxycycline, and "neutrophil-mediated immunity" in trimethoprim were the most involved. Virtual molecular docking analysis showed that all proteins spontaneously bound to their corresponding active compounds. Our analysis suggests that HDW can, directly and indirectly, suppress sebum secretion and exert antiinflammatory effects on acne. Further, HDW may regulate free radicals and suppress apoptosis. Therefore, HDW can be used as an alternative or supplement to standard drugs for acne treatment in patients who cannot use standard treatments due to side effects.Abbreviations: BCL2 = B-cell lymphoma 2, COX-2 = cyclooxygenase 2, GO = gene ontology, HDW = Hedyotis diffusa Willd, IGF1R = insulin-like growth factor-1 receptor, IL = interleukin, KEGG = Kyoto Encyclopedia of Genes and Genomes, MMP = matrix metalloproteinase, NETs = neutrophil extravasation traps, NOS = nitric oxide synthase, NR1H = nuclear receptor subfamily 1 group H member, P. acnes = Propionibacterium acnes, PPAR = peroxisome proliferator-activated receptor, PPI = protein-protein interaction, PTGS2 = prostaglandin-endoperoxide synthase 2, ROS = reactive oxygen species, SMILE = simplified molecularinput-l...

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Based on Network Pharmacology and Molecular Docking to Explore the Underlying Mechanism of Huangqi Gegen Decoction for Treating Diabetic Nephropathy

Cited by 13 publications

References 40 publications

Integrated Bioinformatics and Clinical Correlation Analysis of Key Genes, Pathways, and Potential Therapeutic Agents Related to Diabetic Nephropathy

Integrated Bioinformatics and Clinical Correlation Analysis of Key Genes, Pathways, and Potential Therapeutic Agents Related to Diabetic Nephropathy

Exploration of the possible mechanisms of Ling Gui Zhu Gan decoction in nephrotic syndrome based on network pharmacology, molecular docking and molecular dynamics simulation

Exploring the mechanism of action of Hedyotis diffusa Willd on acne using network analysis

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