Integrated network pharmacology and molecular docking analysis of Aerva sanguinolenta n-hexane extract against breast cancer
DOI:
https://doi.org/10.33503/ebio.v10i02.1609Keywords:
Aerva sanguinolenta, breast cancer, GC-MS, Network Pharmacology, Sambang colokAbstract
Breast cancer, particularly the estrogen receptor-positive (ER-positive) subtype, remains a significant global health challenge. Although Aerva sanguinolenta (AS) has shown Anti-cancer potential, its comprehensive mechanistic effects on breast cancer are still largely unknown. This study aims to uncover the pharmacological effects of AS bioactive compounds on breast cancer using an integrated network pharmacology and molecular docking approach. Bioactive compounds in AS were identified through GC-MS. Compound-target and breast cancer gene interactions were obtained from various databases, followed by protein-protein interaction, Gene Ontology, and KEGG pathway analyses. Molecular docking studies were then used to confirm key interactions. We found that 4 of 103 AS compounds met strict screening criteria, identifying 712 potential gene targets, 33 of which were directly related to breast cancer, including hormonal (ESR1) and apoptosis (AURKA) pathways. Further analysis and molecular docking confirmed the strong binding affinity of Bakuchiol and Afzelin compounds to their main targets, which are involved in critical biological processes such as estrogen receptor signaling, cell cycle regulation, and pathways related to cell proliferation and breast cancer development. In conclusion, this study provides a comprehensive understanding of the potential mechanisms of AS bioactive compounds Afzelin and Bakuchiol against breast cancer, demonstrating their therapeutic potential through Network Pharmacology and docking scores.
References
Agustini, K., Kusumaningrum, S., Firdayani, Sulfianti, A., & Wink, M. (2023a). Estrogenic activity of Bryonia dioica Jacq. through in silico and in vitro studies on pS2 gene expression in the breast cancer cell line MCF-7. Pharmacia, 70(4), 951–958. https://doi.org/10.3897/pharmacia.70.e103478
Anza, M., Endale, M., Cardona, L., Cortes, D., Eswaramoorthy, R., Cabedo, N., Abarca, B., Zueco, J., Rico, H., Domingo-Ortí, I., & Palomino-Schätzlein, M. (2022). Cytotoxicity, antimicrobial activity, molecular docking, drug likeness and dft analysis of benzo[c]phenanthridine alkaloids from roots of zanthoxylum chalybeum. Biointerface Research in Applied Chemistry, 12(2), 1569–1586. https://doi.org/10.33263/BRIAC122.15691586
Balamurugan, A., Evanjaline, M. R., B, P., & V R, M. (2022). Gc-ms analysis of bioactive compounds from the ethanol extract of leaves of neibuhria apetala dunn. International Research Journal of Pharmacy, 8(12), 72–78. https://doi.org/10.7897/2230-8407.0812253
Chakrabarty, N., Haque, Md. T., Ershad, Md., Kabir, Md. A., Shams, Md. R., Tahsin, F., Milonuzzaman, M., Al Haque, Md. M., Hasan, Md. Z., Al Mahabub, A., Rahman, M. M., & Patwary, M. R. U. (2019). Antidiarrheal activity of methanol extract of Piper sylvaticum (roxb.) stem in mice and in silico molecular docking of its isolated compounds. Discovery Phytomedicine, 6(3). https://doi.org/10.15562/phytomedicine.2019.97
Chen, F., Cai, Y., Chen, C., & Zhou, J. (2025). Network pharmacology integrated with molecular docking and experimental validation elucidates the therapeutic potential of Forsythiae Fructus extract against hepatitis B virus-related hepatocellular carcinoma. Frontiers in Oncology, 15. https://doi.org/10.3389/fonc.2025.1571537
Demirtürk, E., Ugur Kaplan, A. B., Cetin, M., Akıllıoğlu, K., Dönmez Kutlu, M., Köse, S., & Aksu, F. (2022). Assessment of Pharmacokinetic Parameters of Daidzein-Containing Nanosuspension and Nanoemulsion Formulations After Oral Administration to Rats. European Journal of Drug Metabolism and Pharmacokinetics, 47(2), 247–257. https://doi.org/10.1007/s13318-021-00746-5
Dewi, K. A., Kusumaningrum, S., Prasetya, N. B. A., Kusumastuti, S. A., Rismana, E., Ngatinem, N., Nuralih, N., & Wulansari, M. T. (2025). Potential of binahong (Anredera cordifolia (Ten.) Steenis) leaf extract as a wound healing agent that inhibits matrix metalloproteinases (MMPs) using in silico and stimulates NIH-3T3 cell proliferation by in vitro assay. Pharmacia, 72. https://doi.org/10.3897/PHARMACIA.72.E135811
Ding, J., Wu, J., Wei, H., Li, S., Huang, M., Wang, Y., & Fang, Q. (2022). Exploring the Mechanism of Hawthorn Leaves Against Coronary Heart Disease Using Network Pharmacology and Molecular Docking. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.804801
El-dien, R. T. M., Maher, S. A., Hisham, M., Saber, E. A., Khedr, A. I. M., Fouad, M. A., Kamel, M. S., & Mahmoud, B. K. (2024). Network pharmacology, molecular docking study, and in vivo validation of the wound healing activity of the Red Sea soft coral Paralemnalia thyrsoides (Ehrenberg 1834) ethanolic extract and bioactive metabolites. Beni-Suef University, Journal of Basic and Applied Sciences, 13(1). https://doi.org/10.1186/s43088-024-00512-x
Elkhalifa, A. E. O., Banu, H., Khan, M. I., & Ashraf, S. A. (2023). Integrated Network Pharmacology, Molecular Docking, Molecular Simulation, and In Vitro Validation Revealed the Bioactive Components in Soy-Fermented Food Products and the Underlying Mechanistic Pathways in Lung Cancer. Nutrients, 15(18). https://doi.org/10.3390/nu15183949
Harahap, A. M., Agustini, K., Nuralih, N., Ningsih, S., Widyastuti, Y., & Bahtiar, A. (2025). LC-HRMS profiling and in vitro total phenolics, total flavonoids, antioxidant and cytotoxicity evaluation on MCF7 breast cancer cell lines of the extracts and fractions of Aerva sanguinolenta from Java, Indonesia. Journal of Applied Pharmaceutical Science, 15(6), 265–276. https://doi.org/10.7324/JAPS.2025.227288
Hassanin, S. O., Hegab, A. M. M., Mekky, R. H., Said, M. A., Khalil, M. G., Hamza, A. A., & Amin, A. (2024). Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer. Marine Drugs, 22(7). https://doi.org/10.3390/md22070328
Jadhav, P. A., Thomas, A. B., Pathan, M. K., Chaudhari, S. Y., Wavhale, R. D., & Chitlange, S. S. (2025). Unlocking the therapeutic potential of unexplored phytocompounds as hepatoprotective agents through integration of network pharmacology and in-silico analysis. Scientific Reports, 15(1), 8425. https://doi.org/10.1038/s41598-025-92868-y
Kamau, S. W., Ngugi, M. P., Mwitari, P. G., & Njeru, S. N. (2024). Network pharmacology, molecular docking and experimental approaches of the anti-proliferative effects of Rhamnus prinoides ethyl-acetate extract in cervical cancer cells. Heliyon, 10(17). https://doi.org/10.1016/j.heliyon.2024.e37324
Kim, J. J., Kurita, T., & Bulun, S. E. (2013). Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer. https://doi.org/10.1210/er.2012-1043
Kristianingsih, A., Soetrisno, Reviono, R., & Wasita, B. (2024). Molecular Docking Study of Quercetin from Ethanol Extract of Mimosa pudica Linn on Asthma Biomarkers. Tropical Journal of Natural Product Research, 8(10), 8640–8645. https://doi.org/10.26538/tjnpr/v8i10.4
Liu, H., Mohammed, S. A. D., Lu, F., Chen, P., Wang, Y., & Liu, S. (2022). Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal Antihypertensive Effect of Gedan Jiangya Decoction. BioMed Research International, 2022. https://doi.org/10.1155/2022/3353464
Liu, M., Wang, Y., Deng, W., Xie, J., He, Y., Wang, L., Zhang, J., & Cui, M. (2024). Combining network pharmacology, machine learning, molecular docking and molecular dynamic to explore the mechanism of Chufeng Qingpi decoction in treating schistosomiasis. Frontiers in Cellular and Infection Microbiology, 14. https://doi.org/10.3389/fcimb.2024.1453529
Łukasiewicz, S., Czeczelewski, M., Forma, A., Baj, J., Sitarz, R., & Stanisławek, A. (2021). Breast cancer—epidemiology, risk factors, classification, prognostic markers, and current treatment strategies—An updated review. In Cancers (Vol. 13, Issue 17). MDPI. https://doi.org/10.3390/cancers13174287
Mouttet, D., Laé, M., Caly, M., Gentien, D., Carpentier, S., Peyro-Saint-Paul, H., Vincent-Salomon, A., Rouzier, R., Sigal-Zafrani, B., Sastre-Garau, X., & Reyal, F. (2016). Estrogen-Receptor, Progesterone-Receptor and HER2 Status Determination in Invasive Breast Cancer. Concordance between Immuno-Histochemistry and MapQuantTM Microarray Based Assay. PLoS ONE, 11(2). https://doi.org/10.1371/journal.pone.0146474
Muslikh, F. A., Samudra, R. R., Ma’arif, B., Ulhaq, Z. S., Hardjono, S., & Agil, M. (2022). In Silico Molecular Docking and ADMET Analysis for Drug Development of Phytoestrogens Compound with Its Evaluation of Neurodegenerative Diseases. Borneo Journal of Pharmacy, 5(4), 357–366. https://doi.org/10.33084/bjop.v5i4.3801
Pinipay, F., Rokkam, R., Botcha, S., & Tamanam, R. R. (2023). Evaluating the anti-urolithiasis potential of Ficus religiosa seed GC MS evaluated phytoconstituents based on their in-vitro antioxidant properties and in-silico ADMET and molecular docking studies. Clinical Phytoscience, 9(1). https://doi.org/10.1186/s40816-023-00359-2
Rosdianto, A. M., Kurniawan, A., Gunadi, J. W., Mahendra, I., Setiawan, I., Goenawan, H., Sylviana, N., Pratiwi, Y. S., Syamsunarno, M. R. A. A., Wahyudianingsih, R., Supratman, U., & Lesmana, R. (2022). DMBA-induced Modulate Estrogen Receptors α and β Breast Cancer’s Animal Model. Majalah Kedokteran Bandung, 54(1), 37–42. https://doi.org/10.15395/mkb.v54n1.2479
Safitri, A., Fatchiyah, F., Sari, D. R. T., & Roosdiana, A. (2020). Phytochemical screening, in vitro anti-oxidant activity, and in silico anti-diabetic activity of aqueous extracts of Ruellia tuberosa L. Journal of Applied Pharmaceutical Science, 10(3), 101–108. https://doi.org/10.7324/JAPS.2020.103013
Sellami, A., Montes, M., & Lagarde, N. (2021). Predicting potential endocrine disrupting chemicals binding to estrogen receptor α (Erα) using a pipeline combining structure-based and ligand-based in silico methods. International Journal of Molecular Sciences, 22(6), 1–28. https://doi.org/10.3390/ijms22062846
Shrihastini, V., Muthuramalingam, P., Adarshan, S., Sujitha, M., Chen, J. T., Shin, H., & Ramesh, M. (2021). Plant derived bioactive compounds, their anti‐cancer effects and in silico approaches as an alternative target treatment strategy for breast cancer: An updated overview. In Cancers (Vol. 13, Issue 24). MDPI. https://doi.org/10.3390/cancers13246222
Smolarz, B., Zadrożna Nowak, A., & Romanowicz, H. (2022a). Breast Cancer—Epidemiology, Classification, Pathogenesis and Treatment (Review of Literature). In Cancers (Vol. 14, Issue 10). MDPI. https://doi.org/10.3390/cancers14102569
Subhan, M., Sanachai, K., Sungthong, B., Datham, S., Ratha, J., & Puthongking, P. (2025). Comparison in vitro and in silico studies of phenolic acids and flavonoids on α-glucosidase inhibition. Journal of Pharmacy and Pharmacognosy Research, 13(1), 311–323. https://doi.org/10.56499/jppres24.2081_13.1.311
Susianti, S., Bahri, S., Hadi, S., Setiawansyah, A., Rachmadi, L., Fadilah, I., & Ratna, M. G. (2025). Integrating The Network Pharmacology and Molecular Docking Confirmed with In Vitro Toxicity to Reveal Potential Mechanism of Non–Polar Fraction of Cyperus rotundus Linn as Anti-Cancer Candidate. Journal of Multidisciplinary Applied Natural Science, 5(1), 56–73. https://doi.org/10.47352/jmans.2774-3047.228
Sympli, H. D. (2021). Estimation of drug-likeness properties of GC–MS separated bioactive compounds in rare medicinal Pleione maculata using molecular docking technique and SwissADME in silico tools. Network Modeling Analysis in Health Informatics and Bioinformatics, 10(1). https://doi.org/10.1007/s13721-020-00276-1
Yan, K., Zhang, R. K., Wang, J. X., Chen, H. F., Zhang, Y., Cheng, F., Jiang, Y., Wang, M., Wu, Z., Chen, X. G., Chen, Z. N., Li, G. J., & Yao, X. M. (2025). Using network pharmacology and molecular docking technology, proteomics and experiments were used to verify the effect of Yigu decoction (YGD) on the expression of key genes in osteoporotic mice. Annals of Medicine, 57(1). https://doi.org/10.1080/07853890.2024.2449225
Downloads
Published
How to Cite
Issue
Section
Citation Check
License
Copyright (c) 2025 Edubiotik : Jurnal Pendidikan, Biologi dan Terapan
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
