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. 2022 Sep 19;14(9):1970.
doi: 10.3390/pharmaceutics14091970.

Molecular Mechanisms of Cassia fistula against Epithelial Ovarian Cancer Using Network Pharmacology and Molecular Docking Approaches

Aqsa Kanwal  1 , Farrukh Azeem  1 , Habibullah Nadeem  1 , Usman Ali Ashfaq  1 , Rana Muhammad Aadil  2 , A K M Humayun Kober  3 , Muhammad Shahid Riaz Rajoka  4 , Ijaz Rasul  1
Affiliations

Molecular Mechanisms of Cassia fistula against Epithelial Ovarian Cancer Using Network Pharmacology and Molecular Docking Approaches

Aqsa Kanwal et al. Pharmaceutics. .

Abstract

Epithelial ovarian cancer (EOC) is one of the deadliest reproductive tract malignancies that form on the external tissue covering of an ovary. Cassia fistula is popular for its anti-inflammatory and anticarcinogenic properties in conventional medications. Nevertheless, its molecular mechanisms are still unclear. The current study evaluated the potential of C. fistula for the treatment of EOC using network pharmacology approach integrated with molecular docking. Eight active constituents of C. fistula were obtained from two independent databases and the literature, and their targets were retrieved from the SwissTargetPrediction. In total, 1077 EOC associated genes were retrieved from DisGeNET and GeneCardsSuite databases, and 800 potential targets of eight active constituents of C. fistula were mapped to the 1077 EOC targets and intersected targets from two databases. Ultimately, 98 potential targets were found from C. fistula for EOC. Finally, the protein-protein interaction network (PPI) topological interpretation revealed AKT1, CTNNB1, ESR1, and CASP3 as key targets. This is the first time four genes have been found against EOC from C. fistula. The major enriched pathways of these candidate genes were established by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) investigations. To confirm the network pharmacology findings, the molecular docking approach demonstrated that active molecules have higher affinity for binding to putative targets for EOC suppression. More pharmacological and clinical research is required for the development of a drug to treat EOC.

Keywords: Cassia fistula; active constituents; anticarcinogenic; epithelial ovarian cancer; gene ontology; molecular docking; network pharmacology.

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Conflict of interest statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The network pharmacology and molecular docking techniques employed in order to predict C. fistula’s potential drug targets for the treatment of EOC depicted graphically.
Figure 2
Figure 2
Venn diagram of potential targets.
Figure 3
Figure 3
Compound–target network of active constituents and potential targets (circle shape shows active constituents and diamond shape shows potential targets).
Figure 4
Figure 4
(A) Analysis and Visualization of PPI network in Cytoscape. (B) Top 10 targets of C. fistula on EOC analyzed by Cytoscape.
Figure 4
Figure 4
(A) Analysis and Visualization of PPI network in Cytoscape. (B) Top 10 targets of C. fistula on EOC analyzed by Cytoscape.
Figure 5
Figure 5
Hub genes enriched in top 20 signaling pathways. Signaling pathways are represented as hexagons and targets are represented as ellipses.
Figure 6
Figure 6
GO analysis of C. fistula’s potential targets on EOC. (A) Biological Processes (BP), (B) Cellular Components (CC), and (C) Molecular Functions (MF).
Figure 6
Figure 6
GO analysis of C. fistula’s potential targets on EOC. (A) Biological Processes (BP), (B) Cellular Components (CC), and (C) Molecular Functions (MF).
Figure 7
Figure 7
KEGG pathway enrichment analysis: 20 enriched pathways plotted through R language.
Figure 8
Figure 8
C. fistula’s compound–target–signaling pathway network to EOC. Candidate active phytochemicals shown as ellipses, potential targets represented as diamonds, and pathways represented as hexagons.
Figure 9
Figure 9
The binding site residues with the four proteins are shown in the docking complex of four targets with their best binding components: (A) AKT1; (B) CTNNB1; (C) ESR1; (D) CASP3.
Figure 9
Figure 9
The binding site residues with the four proteins are shown in the docking complex of four targets with their best binding components: (A) AKT1; (B) CTNNB1; (C) ESR1; (D) CASP3.
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