{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T19:27:42Z","timestamp":1782934062525,"version":"3.54.5"},"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Vernolac is a commercially available polyherbal nutraceutical capsule containing\n                    <jats:italic>Vernonia zeylanica<\/jats:italic>\n                    aerial parts,\n                    <jats:italic>Nigella sativa<\/jats:italic>\n                    seeds,\n                    <jats:italic>Hemidesmus indicus<\/jats:italic>\n                    roots,\n                    <jats:italic>Leucas zeylanica<\/jats:italic>\n                    aerial parts, and\n                    <jats:italic>Smilax glabra<\/jats:italic>\n                    rhizome. Herbal formulations, organic extracts, and isolated phytochemicals from these plants have demonstrated anticancer properties. However, the mechanisms underlying Vernolac\u2019s anticancer activity as a polyherbal formulation remain largely unexplored. This study utilized an integrative network pharmacology-based approach, supported by\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments, to investigate Vernolac\u2019s anticancer potential. Phytochemicals were retrieved from databases, screened for drug-likeness and oral bioavailability using SwissADME, yielding 155 drug-like compounds, and their protein targets were predicted using SwissTargetPrediction. The intersection of phytochemical targets with cancer-related targets from GeneCards identified 137 common targets. Protein-protein interaction analysis using STRING and Cytoscape revealed fourteen key hub nodes, including AKT1, BCL2, CASP3, CTNNB1, EGFR, ESR1, GAPDH, HSP90AA1, HSP90AB1, IL6, JUN, SRC, STAT3, and TNF. Network analyses highlighted key phytochemicals, including vernolactone, thymoquinone, quercetin, nigellidine, \u03b1-hederin, and carvacrol. GC\u2013MS profiling of the supercritical CO\n                    <jats:sub>2<\/jats:sub>\n                    extract of Vernolac revealed a diverse phytochemical composition enriched with terpenes, fatty acids, and sterols, including the key constituents stigmasterol, thymoquinone, and carvacrol. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed significant enrichment of the identified targets across multiple cancer pathways. Molecular docking and dynamics simulations identified novel target-ligand interactions, such as vernolactone-\u03b2-catenin and \u03b1-hederin-CDK4. The Sulforhodamine B assay demonstrated selective antiproliferative activity of Vernolac extract against cancerous cell lines MCF-7 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200954.01\u2009\u00b1\u20090.02 \u03bcg\/mL), Caco-2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200985.52\u2009\u00b1\u20090.13 \u03bcg\/mL), NTERA-2 cl.D1 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200942.41\u2009\u00b1\u20090.06 \u03bcg\/mL), and non-cancerous MCF-10A (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u2009803.5\u2009\u00b1\u20090.03 \u03bcg\/mL). Collectively, network analysis suggests that phytochemicals in Vernolac may exert anticancer effects through multiple cancer-related pathways, including those associated with apoptosis, immune modulation, oxidative stress, inflammation, and cell proliferation. Furthermore, the identified targets and enriched pathways suggest a potential role in modulating drug resistance and treatment response, providing a computational basis for its application as an adjunct to conventional cancer therapies and warranting further investigation in preclinical and clinical settings.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352420","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:44:16Z","timestamp":1782927856000},"page":"e0352420","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A network pharmacology-based approach and molecular docking study to explore the therapeutic potential of a nutraceutical formula (Vernolac) in the treatment of cancer"],"prefix":"10.1371","volume":"21","author":[{"given":"Sandani De","family":"Vass Gunawardane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1115-9902","authenticated-orcid":true,"given":"Matheen Muhammadh","family":"Milhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poorni Chanuka","family":"Rathnayake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabudhi S.","family":"Garusinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavishka S.","family":"Gunaratne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusha","family":"Kanagasundaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. M. D.","family":"Darshanamala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duvinika Chalani","family":"Senevirathne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini Kaushalya","family":"Wijerathne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4795-9306","authenticated-orcid":true,"given":"R. P. C. D.","family":"Perera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanishka Sithira","family":"Senathilake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umapriyatharshini","family":"Rajagopalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0608-4340","authenticated-orcid":true,"given":"Kamani Hemamala","family":"Tennakoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5278-4770","authenticated-orcid":true,"given":"Sameera Ranganath","family":"Samarakoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"issue":"1","key":"pone.0352420.ref001","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13045-024-01640-8","article-title":"Global burden of cancer and associated risk factors in 204 countries and territories, 1980\u20132021: a systematic analysis for the GBD 2021","volume":"17","author":"Z Wu","year":"2024","journal-title":"J Hematol Oncol"},{"issue":"3","key":"pone.0352420.ref002","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"F Bray","year":"2024","journal-title":"Cancer J Clin"},{"issue":"1","key":"pone.0352420.ref003","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s12672-025-02198-8","article-title":"Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy","volume":"16","author":"A Zafar","year":"2025","journal-title":"Discov Oncol"},{"issue":"13","key":"pone.0352420.ref004","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.3390\/cancers16132478","article-title":"Emerging therapeutic strategies to overcome drug resistance in cancer cells","volume":"16","author":"P Garg","year":"2024","journal-title":"Cancers (Basel)"},{"issue":"5","key":"pone.0352420.ref005","doi-asserted-by":"crossref","DOI":"10.1002\/cam4.7010","article-title":"Integrating natural compounds and nanoparticle-based drug delivery systems: a novel strategy for enhanced efficacy and selectivity in cancer therapy","volume":"13","author":"A Manzari-Tavakoli","year":"2024","journal-title":"Cancer Med"},{"key":"pone.0352420.ref006","doi-asserted-by":"crossref","first-page":"5919453","DOI":"10.1155\/2022\/5919453","article-title":"The chemotherapeutic potentials of compounds isolated from the plant, marine, fungus, and microorganism: their mechanism of action and prospects","volume":"2022","author":"AK Shakya","year":"2022","journal-title":"J Trop Med"},{"key":"pone.0352420.ref007","doi-asserted-by":"crossref","first-page":"176","DOI":"10.29228\/ijpbp.30","article-title":"Emerging insights of nutraceuticals as anticancer","volume":"3","author":"S Pant","year":"2023","journal-title":"Int J Plant Based Pharm"},{"issue":"14","key":"pone.0352420.ref008","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.3390\/nu15143249","article-title":"What is the role of nutraceutical products in cancer patients? 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