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

Munazza       Ijaz; Xianju      Huang; Manal       Buabeid; Tahir    Ali    Chohan; Ghulam       Murtaza; Saba       Shamim

doi:10.2174/1570180818666211119113853

Abstract

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.

Keywords: Biological effects, cytoscape, respiratory ailments, mechanism of action, molecular targets, interleukin-6, Glycyrrhiza uralensis, STITCH.

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

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