Revealing the Underlying Mechanism of Acacia Nilotica against Asthma from a Systematic Perspective: A Network Pharmacology and Molecular Docking Study

Abstract

Acacia Nilotica (AN) has long been used as a folk cure for asthma, but little is known about how AN could possibly modulate this disease. Thus, an in-silico molecular mechanism for AN's anti-asthmatic action was elucidated utilizing network pharmacology and molecular docking techniques. DPED, PubChem, Binding DB, DisGeNET, DAVID, and STRING were a few databases used to collect network data. MOE 2015.10 software was used for molecular docking. Out of 51 searched compounds of AN, eighteen compounds interacted with human target genes, a total of 189 compounds-related genes, and 2096 asthma-related genes were found in public databases, with 80 overlapping genes between them. AKT1, EGFR, VEGFA, and HSP90AB were the hub genes, whereas quercetin and apigenin were the most active components. p13AKT and MAPK signaling pathways were found to be the primary target of AN. Outcomes of network pharmacology and molecular docking predicted that AN might exert its anti-asthmatic effect probably by altering the p13AKT and MAPK signaling pathway.

Keywords: Acacia Nilotica; asthma; molecular docking; network pharmacology.

Figure 1

The overworkflow for elucidation of anti-asthmatic potential of Acacia Nilotica.

Figure 2

A Venn diagram showing overlapping genes between 2096 asthma-related genes (A) and 189 compounds related genes (B).

Figure 3

Network with 99 nodes and 206 edges linking 18 compounds of Acacia Nilotica with 80 genes of Asthma. The red-colored nodes in the network’s center indicate AN components, while the purple-colored nodes reflect asthma’s potential targets.

Figure 4

Protein-protein interaction (PPI) network analysis.

Figure 5

Gene Ontology (GO) enrichment analysis of the target proteins. Biological process (orange), molecular function (blue) and cellular component (green).

Figure 6

Bar chart of top 10 signaling pathways.

Figure 7

p13-AKT signaling pathways. Red boxes represent the genes of the pathway targeted by compounds of AN.

Figure 8

Network of compound-target-pathway where blue colored rhomboid boxes represents targets, red square nodes represent compounds and purple colored octagons represents pathways.

Figure 9

Apigenin and Quercetin possible binding modalities in the binding pockets of the specified targets. A green dotted line shows side-chain proton acceptor/donors, while a purple dotted line shows metal or ion contact. The blue and red circles, which represent basic and acidic amino acids, respectively. Because they have been exposed to solvents, some amino acids have a blue background. Additionally, the blue coloring of the ligand atoms in front of them indicates solvent exposure.