Molecular docking and network connections of active compounds from the classical herbal formula Ding Chuan Tang

Background Ding Chuan Tang (DCT), a traditional Chinese herbal formula, has been consistently prescribed for the therapeutic management of wheezing and asthma-related indications since the Song Dynasty (960–1279 AD). This study aimed to identify molecular network pharmacology connections to understand the biological asthma-linked mechanisms of action of DCT and potentially identify novel avenues for asthma drug development. Methods Employing molecular docking (AutoDock Vina) and computational analysis (Cytoscape 3.6.0) strategies for DCT compounds permitted examination of docking connections for proteins that were targets of DCT compounds and asthma genes. These identified protein targets were further analyzed to establish and interpret network connections associated with asthma disease pathways. Results A total of 396 DCT compounds and 234 asthma genes were identified through database search. Computational molecular docking of DCT compounds identified five proteins (ESR1, KDR, LTA4H, PDE4D and PPARG) mutually targeted by asthma genes and DCT compounds and 155 docking connections associated with cellular pathways involved in the biological mechanisms of asthma. Conclusions DCT compounds directly target biological pathways connected with the pathogenesis of asthma including inflammatory and metabolic signaling pathways.

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Mechanistic Investigation of Glycyrrhiza uralensis Effects against Respiratory Ailments: Application of Network Pharmacology and Molecular Docking Approaches

Letters in Drug Design & Discovery ◽

10.2174/1570180818666211119113853 ◽

2021 ◽

Vol 18 ◽

Author(s):

Munazza Ijaz ◽

Xianju Huang ◽

Manal Buabeid ◽

Tahir Ali Chohan ◽

Ghulam Murtaza ◽

...

Keyword(s):

Gene Ontology ◽

Molecular Docking ◽

Herbal Remedy ◽

Database Search ◽

Glycyrrhiza Uralensis ◽

Network Pharmacology ◽

Careful Study ◽

Protein Targets ◽

Go Enrichment ◽

Mechanistic Investigation

Background: Glycyrrhiza uralensis, also known as liquorice, is a herbal remedy that is traditionally used worldwide for treating respiratory ailments and ameliorating breathing. Objective: The objective of this systematic study was to investigate active ingredients of Glycyrrhiza uralensis and determine its mode of action in silico against severe and acute respiratory complications of respiratory ailments through network pharmacology and molecular docking studies. Methods: TCMSP database search helped retrieve the compounds of Glycyrrhiza uralensis and their protein targets, especially related to respiratory ailments. Subsequently, the protein-protein association was attained as a network by using the STITCH database. Cytoscape and its ClueGO plugin were used to study gene ontology (GO) enrichment. In addition, seven natural compounds were docked in the active site of four different molecular targets; JUN-FOS, COX2, MAPK14 and IL-6, to identify the binding mechanism of ligands under study. Results: TCMSP database search resulted in the retrieval of 280 compounds of Glycyrrhiza uralensis (including formononetin, naringenin, sitosterol, isorhamnetin, kaempferol, quercetin and Glycyrrhizin) and 135 protein targets. A careful study of targets showed that 26 prospective targets (including JUN, FOS, IL6, MAPK14 and PTGS2) related to respiratory ailments were identified. Gene ontology (GO) enrichment analysis resulted in the retrieval of 176 GO terms, which were associated with respiratory ailments. This study proposed that Glycyrrhiza uralensis acts against respiratory ailments through various proteins, such as JUN, FOS, IL6, MAPK14 and PTGS2. Docking results revealed that among all studied ligands, the flavonoid-based compounds isorhamnetin and kaempferol form stronger complexes with JUN-FOS-DNA, MAPK-14, and IL-6 proteins (Cscore=6.81, 4.27, and 4.77, respectively) and the saponin based compound glycyrrhizin (Cscore=13.07) demonstrated stronger binding affinity towards COX2 enzyme. Conclusion: Conclusively, isorhamnetin, kaempferol and glycyrrhizin in Glycyrrhiza uralensis may regulate several signaling pathways through JUN-FOS-DNA, MAPK-14, and IL-6, which might play a therapeutic role against respiratory ailments.

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Network Pharmacology Analysis and Molecular Characterization of the Herbal Medicine Formulation Qi-Fu-Yin for the Inhibition of the Neuroinflammatory Biomarker iNOS in Microglial BV-2 Cells: Implication for the Treatment of Alzheimer’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/5780703 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Fung Yin Ngo ◽

Weiwei Wang ◽

Qilei Chen ◽

Jia Zhao ◽

Hubiao Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Selective Inhibition ◽

Network Pharmacology ◽

Herbal Formula ◽

Active Compounds ◽

Protein Targets ◽

Blotting Technique ◽

Cox 2 ◽

Angelicae Sinensis

Aberrant microglial activation drives neuroinflammation and neurodegeneration in Alzheimer’s disease (AD). The present study is aimed at investigating whether the herbal formula Qi-Fu-Yin (QFY) could inhibit the inflammatory activation of cultured BV-2 microglia. A network pharmacology approach was employed to predict the active compounds of QFY, protein targets, and affected pathways. The representative pathways and molecular functions of the targets were analyzed by Gene Ontology (GO) and pathway enrichment. A total of 145 active compounds were selected from seven herbal ingredients of QFY. Targets (e.g., MAPT, APP, ACHE, iNOS, and COX-2) were predicted for the selected active compounds based on the relevance to AD and inflammation. As a validation, fractions were sequentially prepared by aqueous extraction, ethanolic precipitation, and HPLC separation, and assayed for downregulating two key proinflammatory biomarkers iNOS and COX-2 in lipopolysaccharide- (LPS-) challenged BV-2 cells by the Western blotting technique. Moreover, the compounds of QFY in 90% ethanol downregulated iNOS in BV-2 cells but showed no activity against COX-2 induction. Among the herbal ingredients of QFY, Angelicae Sinensis Radix and Ginseng Radix et Rhizoma contributed to the selective inhibition of iNOS induction. Furthermore, chemical analysis identified ginsenosides, especially Rg3, as antineuroinflammatory compounds. The herbal formula QFY may ameliorate neuroinflammation via downregulating iNOS in microglia.

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New perspective: the multi-targets mechanism of hydroxychloroquine in the treatment of rheumatoid arthritis based on network pharmacology

10.21203/rs.3.rs-65359/v1 ◽

2020 ◽

Author(s):

Bo Xie ◽

Haojie Lu ◽

Jinhui Xu ◽

Yebei Hu ◽

Haixin Luo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Docking ◽

Drug Targets ◽

Cell Activation ◽

Acid Amide ◽

Network Pharmacology ◽

Protein Targets ◽

Protein Protein Interaction ◽

Amide Hydrolase ◽

New Perspective

Abstract Background Network pharmacology is a new method of bioinformatics in exploring drug targets in recent 3 years. Hydroxychloroquine (HCQ) is a multi-targets drug that are clinically effective in rheumatoid arthritis (RA) but whose mechanism is not well understood. Methods The predicted targets of HCQ and the proteins related to RA were returned from databases. Followed by protein-protein interaction (PPI) network, the intersection of the two group of proteins was conducted. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment was used to analyse these proteins in a macro perspective. Finally, the candidate targets were verified by molecular docking. Results The results suggest that the efficacy of HCQ against RA is mainly associated with 4 targets of smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH), with their related 3316 proteins’ network which regulate ErbB, HIF-1, NF-κB, FoxO, Chemokine, MAPK, PI3K/Akt pathways and so forth. Biological process are mainly concentrated in the regulation of cell activation, myeloid leukocyte activation, regulated exocytosis and so forth. Molecular docking analysis shows that hydrogen bonding and π-π stacking are the main forms of chemical force. Conclusions Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3316 proteins become the multi-targets mechanism of HCQ in the treatment of RA. As well, the research also provides a new idea for introducing network pharmacology into the evaluation of the multi-target drugs in internal medicine.

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