NETWORK PHARMACOLOGY AND MOLECULAR DOCKING-BASED INVESTIGATION OF CALOTROPIS GIGANTEA LINN. LEAF EXTRACT AGAINST VULVOVAGINAL CANDIDIASIS

VASUNDHARA B BHOSALE; AKSHADA AMIT KOPARDE; VANDANA M THORAT; MAYURI V BHOSALE

doi:10.22159/ajpcr.2025v18i12.56803

Authors

VASUNDHARA B BHOSALE Department of Pharmaceutical Sciences, Krishna Institute of Pharmacy, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India. https://orcid.org/0009-0004-7905-2790
AKSHADA AMIT KOPARDE Department of Pharmaceutical Chemistry, Krishna Institute of Pharmacy, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India. https://orcid.org/0000-0002-6353-9930
VANDANA M THORAT Department of Pharmacology, Krishna Institute of Medical Science, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India.
MAYURI V BHOSALE Department of Pharmaceutical Sciences, Krishna Institute of Pharmacy, Krishna Vishwa Vidyapeeth (Deemed to be University), Karad, Maharashtra, India. https://orcid.org/0009-0009-6065-5280

DOI:

https://doi.org/10.22159/ajpcr.2025v18i12.56803

Keywords:

Network Pharmacology, vulvovaginal candidiasis, Calotropis gigantea Linn, molecular docking, 3,6-Octadienal, 3,7-dimethyl-.

Abstract

Objectives: This study aimed to elucidate the multitarget therapeutic mechanisms of Calotropis gigantea leaf extract against vulvovaginal candidiasis (VVC) using a network pharmacology (NP) approach integrated with molecular docking.

Methods: Gas chromatography-mass spectrometry (GC-MS) analysis of the methanolic extract of C. gigantea leaves identified 38 phytochemicals. Drug-likeness was assessed through SwissADME, and target prediction was performed using Super-PRED and UniProt. VVC-related genes from GeneCards were compared using Venny, and common targets were analyzed through STRING for protein–protein interaction. Pathway enrichment and network construction were done through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cytoscape. Key compounds were docked with hub protein toll-like receptor 4 (TLR4) using Molsoft ICM.

Results: GC-MS identified key bioactives like 3,6-Octadienal, 3,7-dimethyl- and 1,3,8-p-Menthatriene. Ten overlapping targets with VVC genes were found, with TLR4 as a major hub. KEGG analysis highlighted four pathways, including Toll-like receptor signaling. Docking revealed strong binding of 3,6-Octadienal, 3,7-dimethyl- to TLR4 (−24.9 kcal/mol), exceeding clotrimazole (-18.82 kcal/mol).

Conclusion: C. gigantea Linn. shows promise as a multi-target antifungal agent against VVC by modulating immune pathways. NP and docking highlight 3,6-Octadienal, 3,7-dimethyl, as a key bioactive. Among the identified compounds, 3,6-Octadienal, 3,7-dimethyl- exhibited the strongest binding affinity toward TLR4; however, its low concentration (0.11% relative peak area) indicates that its biological impact may be limited and potentially synergistic with other more abundant phytoconstituents. Further in vitro and in vivo studies are needed to validate these findings and develop clinical formulations.

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