Deciphering the Molecular Mechanism of Butea monosperma Flowers Against Cervical Cancer: An Integrated Network Pharmacology, Molecular Docking, and MD Simulation Approach
Keywords:
Butea monosperma, Cervical Cancer, Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations, Hub Genes, Apoptosis.
Abstract
Cervical cancer remains a critical global health challenge, ranking as the fourth leading cause of cancer-related mortality among women, particularly in low-resource regions. Because conventional treatments are often limited by low efficacy and adverse off-target effects, there is a pressing need to discover multi-targeted therapeutic agents from natural sources. This study utilizes an integrated approach—combining systems pharmacology, molecular docking, and molecular dynamics simulations—to elucidate the anti-cancer potential of Butea monosperma Taub. flowers.
Through extensive database screening, 21 phytochemical constituents were identified, of which six compounds demonstrated optimal pharmacokinetic profiles and strict adherence to drug-likeness filters. A multi-layered network analysis revealed 598 common targets between B. monosperma and cervical cancer, identifying ten core hub genes: TP53, EGFR, SRC, HSP90AA1, STAT3, AKT1, TNF, HSP90AB1, BCL2, and HIF1A. Molecular docking analysis demonstrated high binding affinities, with Isobutrin showing superior potential against SRC, Monospermoside against AKT1, and Coreopsin against EGFR.
Functional enrichment through GO and KEGG pathways indicated that these phytochemicals primarily modulate the PI3K/AKT/mTOR and IL-6/STAT3 signaling axes to induce apoptosis and cell cycle arrest. MD simulations further validated the thermodynamic stability of these protein-ligand interactions, yielding low eigenvalues and significant rigidification of the binding pockets. These findings provide a rigorous computational foundation for using B. monosperma flowers as a source of potent, multi-targeted inhibitors for the management of cervical malignancy
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2. Ma Y, Lai X, Fang H. Global, regional, and national disease burden and economic costs of cervical cancer (1991–2021): a multidimensional data synthesis analysis. Frontiers in Public Health [Internet]. 2025 Sep 11 [cited 2025 Oct];13. Available from: https://doi.org/10.3389/fpubh.2025.1633975
3. Huang S, Wang R, Song Y, Liao SM, Ou M, Huang Y, et al. Uncovering the anti-cervical cancer mechanism of Ziyuglycoside I via integrated network pharmacology molecular docking and experimental validation. Scientific Reports [Internet]. 2025 Oct 16 [cited 2025 Oct];15(1). Available from: https://doi.org/10.1038/s41598-025-20129-z
4. Zhou J, Li H, Wu B, Zhu L, Huang Q, Guo Z, et al. Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer. Scientific Reports [Internet]. 2024 Jan 22 [cited 2025 Oct];14(1). Available from: https://doi.org/10.1038/s41598-024-52413-9
5. Bhattacharya K, Nath BC, Ahmed E, Khanal P, Chanu NR, Deka S, et al. Integration of network pharmacology, molecular docking, and simulations to evaluate phytochemicals from Drymaria cordata against cervical cancer. 2024 Jan 1 [cited 2025 Oct]; Available from: https://doi.org/10.1039/d3ra06297j
6. Jain S, Dubey PK. Butea monosperma (Lam.) Taub: Review on its chemistry, morphology, ethnomedical uses, phytochemistry and pharmacological activities. Journal of Drug Delivery and Therapeutics [Internet]. 2023 Apr 15 [cited 2025 Oct];13(4):137. Available from: https://doi.org/10.22270/jddt.v13i4.5782
7. Dua R, Bhardwaj T, Ahmad I, Somvanshi P. Investigating the potential of Juglans regia phytoconstituents for the treatment of cervical cancer utilizing network biology and molecular docking approach. 2024 Apr 16 [cited 2025 Oct]; Available from: https://doi.org/10.1371/journal.pone.0287864
8. Aarthy M, Muthuramalingam P, Ramesh M, Singh SK. Unraveling the multi-targeted curative potential of bioactive molecules against cervical cancer through integrated omics and systems pharmacology approach. 2022 Aug 21 [cited 2025 Oct]; Available from: https://doi.org/10.1038/s41598-022-18358-7
9. Bai X, Ma Y, Zhang G. Butein suppresses cervical cancer growth through the PI3K/AKT/mTOR pathway. 2015 Apr 24 [cited 2025 Aug]; Available from: https://doi.org/10.3892/or.2015.3922
10. Park S, Seo YJ, Kim LK, Kim HJ, Yoon KD, Heo T. Butein Inhibits Cell Growth by Blocking the IL-6/IL-6Rα Interaction in Human Ovarian Cancer and by Regulation of the IL-6/STAT3/FoxO3a Pathway. 2023 Mar 23 [cited 2026 Mar]; Available from: https://doi.org/10.3390/ijms24076038
11. Wu J, Jin Q, Zhang Y, Ji Y, Li J, Liu X, et al. Global burden of cervical cancer: current estimates, temporal trend and future projections based on the GLOBOCAN 2022. 2025 Jan 23 [cited 2025 Nov]; Available from: https://doi.org/10.1016/j.jncc.2024.11.006
12. Kamau SW, Jepkorir M, Kipkoech G, Lagu IJL, Kanda W, Kibunja S, et al. Antiproliferative activity of Grewia villosa ethyl acetate extract on cervical cancer HeLa cell line: Mechanistic insights through network pharmacology and functional assays approach. PLoS ONE [Internet]. 2025 Sep 24 [cited 2025 Sep];20(9). Available from: https://doi.org/10.1371/journal.pone.0331649
13. Yuan Z, Pan Y, Leng T, Yu C, Zhang H, Ma J, et al. Progress and Prospects of Research Ideas and Methods in the Network Pharmacology of Traditional Chinese Medicine. Journal of Pharmacy & Pharmaceutical Sciences [Internet]. Canadian Society for Pharmaceutical Sciences; 2022 Jun 21 [cited 2025 Oct];25:218. Available from: https://doi.org/10.18433/jpps32911
14. MT M, Ranjith D, Yaligar R, Jyothi R, Narappa G, Mv R. Swiss ADME prediction of phytochemicals present in Butea monosperma (Lam.) Taub. Journal of Pharmacognosy and Phytochemistry [Internet]. 2020 Jan 1 [cited 2025 Oct];9(3):1799. Available from: https://www.phytojournal.com/archives/2020/vol9issue3/PartAD/9-3-296-345.pdf
15. Yang P, Hu D, Kao YH, Lin I, Liu F. Butein induces apoptotic cell death of human cervical cancer cells. Oncology Letters [Internet]. 2018 Sep 7 [cited 2025 Sep]; Available from: https://doi.org/10.3892/ol.2018.9426
16. Chen Y, Yeh C, Lo H, Su S, Hseu Y, Hsu L. Generation of reactive oxygen species mediates butein-induced apoptosis in neuroblastoma cells. Oncology Reports [Internet]. 2012 Jan 12 [cited 2025 Jul];27(4):1233. Available from: https://doi.org/10.3892/or.2012.1632
17. Ralte L, Sailo H, Kumar R, Khiangte L, Kumar NS, Singh YT. Identification of novel AKT1 inhibitors from Sapria himalayana bioactive compounds using structure-based virtual screening and molecular dynamics simulations. BMC Complementary Medicine and Therapies [Internet]. 2024 Mar 7 [cited 2025 Oct];24(1). Available from: https://doi.org/10.1186/s12906-024-04415-3
18. Kong L, Deng Z, Shen H, Zhang Y. Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through down-regulating phospho-Src-Y416 and phospho-EGFR-Y1173. Molecular and Cellular Biochemistry [Internet]. 2010 Nov 3 [cited 2026 Jan];348:11. Available from: https://doi.org/10.1007/s11010-010-0632-1
19. Rahimi-Moghaddam A, Ghorbanmehr N, Gharbi S, Nili F, Korsching E. Interplay of miR-542, miR-126, miR-143 and miR-26b withPI3K-AKT is a diagnostic signal and putative regulatory target in HPV-Positive Cervical Cancer. Research Square (Research Square) [Internet]. 2024 Jan 5 [cited 2025 Sep]; Available from: https://doi.org/10.21203/rs.3.rs-3831690/v1
20. Meng M, Guo Y, Chen Y, Li X, Zhang B, Xie Z, et al. Cancer/testis-45A1 promotes cervical cancer cell tumorigenesis and drug resistance by activating oncogenic SRC and downstream signaling pathways. Cellular Oncology [Internet]. 2023 Nov 4 [cited 2025 Aug];47(2):657. Available from: https://doi.org/10.1007/s13402-023-00891-w
Published
2024-06-28
How to Cite
Suresh Kumar Gopal, Rakesh Kumar Jatt, & Abdul Mannan Khan. (2024). Deciphering the Molecular Mechanism of Butea monosperma Flowers Against Cervical Cancer: An Integrated Network Pharmacology, Molecular Docking, and MD Simulation Approach. Revista Electronica De Veterinaria, 25(1), 4583 - 4602. https://doi.org/10.69980/redvet.v25i1.2411
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