NETWORK PHARMACOLOGY BASED COMPUTATIONAL STUDY TO INVESTIGATE THE POTENTIAL MECHANISM OF SYZYGIUM CARYOPHYLLATUM AGAINST COLON CANCER

RAMADEVI PEMMEREDDY; AJAY MILI; BHARATH HAROHALLI BYREGOWDA; JYOTHI GIRIDHAR; SREEDHARA RANGANATH PAI K; ANNA MATHEW; VASUDEV  PAI; CHANDRASHEKAR K. S

doi:10.22159/ijap.2025v17i1.52490

Authors

RAMADEVI PEMMEREDDY Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India https://orcid.org/0000-0003-3667-1781
AJAY MILI Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India https://orcid.org/0000-0002-0718-6114
BHARATH HAROHALLI BYREGOWDA Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India https://orcid.org/0000-0002-1362-2090
JYOTHI GIRIDHAR Department of Pharmaceutical chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India https://orcid.org/0009-0000-7274-711X
SREEDHARA RANGANATH PAI K Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India https://orcid.org/0000-0002-2017-9533
ANNA MATHEW Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India
VASUDEV PAI Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India https://orcid.org/0000-0002-5147-6389
CHANDRASHEKAR K. S Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India https://orcid.org/0000-0003-3667-1781

DOI:

https://doi.org/10.22159/ijap.2025v17i1.52490

Keywords:

Syzygium caryophyllatum, GC-MS analysis, SRB assay, Network pharmacology, Molecular docking

Abstract

Objective: Syzygium caryophyllatum, a traditional medicinal plant from the Myrtaceae family, is rich in potential phytoconstituents. Based on its ethnobotanical uses and documented pharmacological activities, present work was conducted to evaluate the probable mechanism of action of S. caryophyllatum to manage colon cancer by integrating network pharmacology and computational studies.

Methods: The plant extract was prepared by Soxhlet extraction method and in vitro screening was performed using Sulforhodamine (SRB) Assay on HT 29 cancer cell lines. We have used super-PRED database, Cytoscape network analyser tool, string database and CytoHubba for performing network analysis for the extract compounds reported in GC-MS analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and DAVID databases were used for gene set enrichment analysis. We have used Schrödinger suite Version 11.4's to perform computational studies.

Results: The extract has demonstrated significant in vitro cytotoxic activity (IC50 value is 49.01 µg/ml) and the GC-MS analysis identified seventy-six distinct compounds. The Gene Ontology (GO) and KEGG demonstrated that the shared targets were strongly associated with key processes involved in colon cancer. The current study has identified Estrogen Receptor Alpha (ESR1), Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1), Mitogen-activated protein kinase 3 (MAP3K), Epidermal Growth Factor Receptor (EGFR) and Signal transducer and activator of transcription 3 (STAT3) proteins as essential targets and 5,7-Dihydroxy-2-undecyl-4H-chromen-4-one, 7a,12-Dihydroindolo[2,3-a] quinolizine, 5-hydroxy-7-methoxy-2-methyl-8-(3-methylbutyl) chromen-4-one as key compounds. Docking studies of the compounds with core proteins completely supplemented their binding affinity and suggested strong interactions at the binding site.

Conclusion: These outcomes highlight the multi-target, multi-compound, and multi-pathway approaches of S. caryophyllatum against colon cancer.

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