System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and Huanglian for Diabetes Mellitus

Yue, Shi‐Jun; Liu, Juan; Feng, Wuwen; Zhang, Feilong; Chen, Jianxin; Xin, Lan-Ting; Peng, Cheng; Guan, Huashi; Wang, Chang‐Yun; Yan, Dan

doi:10.3389/fphar.2017.00694

Cited by 118 publications

(85 citation statements)

References 73 publications

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“…Comprehensive determination of potential compound-target interaction profiles is a critical step for the system biology analysis [30]. Currently, multiple databases/platforms, such as DrugBank Database, Comparative Toxicogenomics Database (CTD), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), were commonly applied to acquire potential targets of small molecular compounds [31][32][33]. DrugBank contains detailed drug, drug-target, drug action and drug interaction information about FDA-approved drugs as well as experimental drugs [34].…”

Section: Gene Target Acquisition and Screeningmentioning

confidence: 99%

A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis

Chen¹,

Hu²,

Hood

et al. 2020

Nutrients

114

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Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.

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Section: Gene Target Acquisition and Screeningmentioning

confidence: 99%

A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis

Chen¹,

Hu²,

Hood

et al. 2020

Nutrients

114

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“…TCM not only focuses on improving the symptoms of patients, but also pays attention to the adjustment of the patient's constitution and improve the quality of life of patients [4]. Huangqi, a classic TCM and a representative of tonic herbs with "Gan flavor" and "Wen nature," is extensively used to strengthen "Qi" and "blood" [5]. According to clinical manifestations in TCM, HF can be classified as "chuan zheng" or "shui zhong," which is usually related to the insufficiency of "Qi" and "blood" and always combined with phlegm-dampness and/or blood stasis.…”

Section: Introductionmentioning

confidence: 99%

“…Insufficiency of "Qi" and "blood" will lead to the energy of tissues, urine and body fluid stagnation [5]. e "Gan flavor" and "Wen nature" are acknowledged as the effective treatment to reinforce "Qi" and improve "chuan zheng" or "shui zhong" syndrome.…”

Section: Introductionmentioning

confidence: 99%

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Tao

Huang

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.

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“…A new approach that analyzes TCM with network pharmacology may be a reliable way to overcome disease [49]. Cumulating data have shown that network pharmacology can reveal the interactions between multiple targets of compounds present in Chinese herbal medicines [50].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis

Tao

Tian

Chen

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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This study aims to predict the active ingredients, potential targets, signaling pathways and investigate the “ingredient-target-pathway” mechanisms involved in the pharmacological action of Danshiliuhao Granule (DSLHG) on liver fibrosis. Pharmacodynamics studies on rats with liver fibrosis showed that DSLHG generated an obvious anti-liver fibrosis action. On this basis, we explored the possible mechanisms underlying its antifibrosis effect using network pharmacology approach. Information about compounds of herbs in DSLHG was collected from TCMSP public database and literature. Furthermore, the oral bioavailability (OB) and drug-likeness (DL) were screened according to ADME features. Compounds with OB≥30% and DL≥0.18 were selected as active ingredients. Then, the potential targets of the active compounds were predicted by pharmacophore mapping approach and mapped with the target genes of the specific disease. The compound-target network and Protein-Protein Interaction (PPI) network were built by Cytoscape software. The core targets were selected by degree values. Furthermore, GO biological process analysis and KEGG pathway enrichment analysis were carried out to investigate the possible mechanisms involved in the anti-hepatic fibrosis effect of DSLHG. The predicted results showed that there were 108 main active components in the DSLHG formula. Moreover, there were 192 potential targets regulated by DSLHG, of which 86 were related to liver fibrosis, including AKT1, EGFR, and IGF1R. Mechanistically, the anti-liver fibrosis effect of DSLHG was exerted by interfering with 47 signaling pathways, such as PI3K-Akt, FoxO signaling pathway, and Ras signaling pathway. Network analysis showed that DSLHG could generate the antifibrosis action by affecting multiple targets and multiple pathways, which reflects the multicomponent, multitarget, and multichannel characteristics of traditional Chinese medicine and provides novel basis to clarify the mechanisms of anti-liver fibrosis of DSLHG.

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System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and Huanglian for Diabetes Mellitus

Cited by 118 publications

References 73 publications

A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis

A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Network Pharmacology-Based Prediction of the Active Compounds, Potential Targets, and Signaling Pathways Involved in Danshiliuhao Granule for Treatment of Liver Fibrosis

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