{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:13:49Z","timestamp":1753892029877,"version":"3.41.2"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The cortex mori comes from the white endothelium of the young root of Morus alba L., and its medical value was first described in Shen Nong Ben Cao Jing (Classic on Materia Medical of Shennong). It was originally intended to purge lung, relieve asthma and reduce swelling. More and more studies reported that its pharmacological effects include analgesic, anti-inflammatory, antitussive, antiasthmatic, hypoglycemic, hypolipidemic and anti-diabetic peripheral neuropathy. Accumulating clinical evidences exhibited that it can treat asthma, pneumonia and lung cancer. However, a comprehensive mechanism of cortex mori in the treatment of lung cancer needs to be further elucidated.To investigate the effect of cortex mori and its active components against lung cancer and explore its action and mechanism through network pharmacological analysis combined with biological experiments <jats:italic>in vitro<\/jats:italic> and <jats:italic>In vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>GeneCards database was searched for the disease targets of lung cancer, and a Chinese medicine database, Traditional Chinese Medicine Systems Pharmacology (TCMSP), was used to screen cortex mori for its active components and targets. Targets related to lung cancer and action targets related to cortex mori were crossed. Protein-protein interactions (PPI) and gene ontologies (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for intersection genes. In order to determine whether cortex mori affects lung cancer, MTS, wound healing, Western-blot, Hoechst assay, apoptosis assay and animal experiments were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>32 active ingredients and 434 targets of Chinese medicine cortex mori were obtained. Totally 2,3107 lung cancer related targets were collected, and 163 Chinese medicine-disease targets were derived from the intersection. The regulatory network of Chinese medicine-active ingredient-disease-targets showed that cortex mori acted on 163 disease targets of lung cancer mainly by cyclomolorusin, kuwanon D and Moracin A, etc. The core genes involving cortex mori treating lung cancer might consist of JUN, AKT1, etc. The core targets involved 162 biological processes, mainly including nuclear receptor activity, ligand-actived transcription factor activity, etc. The core study targeted 160 pathways, including AGE-RAGE signaling pathways associated with diabetes complications, fluid stress and atherosclerosis. Biologic cytological experiments showed that the effective active component cyclomorusin inhibited proliferation, inhibited migration and induced apoptosis of lung cancer through AKT-PI3K pathway. <jats:italic>In vivo<\/jats:italic> antitumor assay demonstrated that cyclomolorusin suppressed the tumor growth in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Cortex mori acts on AKT and other related disease targets of lung cancer cells through effective components such as cyclomolorusin, and plays a role in the treatment of lung cancer by inhibiting the signaling pathway associated with lung cancer occurrence and development.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1587856","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T05:24:45Z","timestamp":1748496285000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular targets and mechanisms of cortex mori for lung cancer treatment: a network pharmacology study, molecular docking and in vitro and in vivo experimental validation"],"prefix":"10.3389","volume":"15","author":[{"given":"Ying-Ying","family":"Shao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu-Hong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Fen","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Chao","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-Cheng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui-Rong","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Xin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e1422","DOI":"10.1002\/cnr2.1422","article-title":"Verification of the eighth edition of the UICC-TNM classification on surgically resected lung adenocarcinoma: Comparison with previous classification in a local center","volume":"5","author":"Minato","year":"2021","journal-title":"Cancer Rep"},{"key":"B2","doi-asserted-by":"publisher","first-page":"106805","DOI":"10.1016\/j.ejps.2024.106805","article-title":"Evaluation of drug resistance for EGFR-TKIs in lung cancer via multicellular lung-on-a-chip","volume":"199","author":"Tan","year":"2024","journal-title":"Eur J Pharm Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"37","DOI":"10.5588\/ijtld.23.0224","article-title":"Anti-tuberculosis activity of morusin: a promising flavonoid from white mulberry","volume":"28","author":"Yildirim","year":"2024","journal-title":"Int J Tuberc Lung Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.3390\/ijms20092244","article-title":"The Root Bark of Morus alba L. Suppressed the Migration of Human Non-Small-Cell Lung Cancer Cells through Inhibition of Epithelial- Mesenchymal Transition Mediated by STAT3 and Src","volume":"20","author":"Min","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1515\/hmbci-2021-0100","article-title":"Anti-migratory effect of curcumin on A-549 lung cancer cells via epigenetic reprogramming of RECK\/matrix metalloproteinase axis","volume":"43","author":"Mostofi","year":"2022","journal-title":"Horm Mol Biol Clin Investig"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/BF02976562","article-title":"Cortex mori extract induces cancer cell apoptosis through inhibition of microtubule assembly","volume":"25","author":"Nam","year":"2002","journal-title":"Arch Pharm Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1007279","article-title":"Cortex Mori extracts induce apoptosis and inhibit tumor invasion via blockage of the PI3K\/AKT signaling in melanoma cells","volume":"13","author":"Hu","year":"2022","journal-title":"Front Pharmacol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2012.1386","article-title":"Role of autophagy in apoptosis induction by methylene chloride extracts of Moil codex in NCI-H460 human lung carcinoma cell","volume":"40","author":"Park","year":"2012","journal-title":"Int J Oncol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"9420084","DOI":"10.26599\/fmh.2026.9420084","article-title":"Exploring anti-tumor potential of food and medicine homology substances: An in-silico evaluation of Citri Grandis Exocarpium against gallbladder cancer","volume":"3","author":"Li","year":"2026","journal-title":"FMH"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1525210","article-title":"Exploring manzamine a: a promising anti-lung cancer agent from marine sponge Haliclona sp","volume":"16","author":"Su","year":"2025","journal-title":"Front Pharmacol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"119696","DOI":"10.1016\/j.jep.2025.119696","article-title":"Exploring the mechanism of Sinisan in the treatment of ulcerative colitis with depression based on UPLC-Q-Orbitrap-MS combined with network pharmacology, molecular docking, and experimental validation","volume":"347","author":"Zheng","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e35404","DOI":"10.1097\/MD.0000000000035404","article-title":"Exploring traditional Chinese medicine as a potential treatment for sarcopenia: A network pharmacology and data mining analysis of drug selection and efficacy","volume":"102","author":"Zhou","year":"2023","journal-title":"Medicine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2013.02.004","article-title":"Systems approaches and polypharmacology for drug discovery from herbal medicines: An example using licorice","volume":"146","author":"Liu","year":"2013","journal-title":"J Ethnopharmacol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14675","article-title":"Tianfoshen oral liquid: A CFDA approved clini-cal traditional Chinese medicine, normalizes major cellular pathways disor-dered during colorectal carcinogenesis","volume":"8","author":"Wang","year":"2017","journal-title":"OT"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S1674-6384(16)60018-7","article-title":"Network pharmacology-based approaches capture essence of Chinese herbal medicines","volume":"8","author":"Zhang","year":"2016","journal-title":"Chin He Medi"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms13066964","article-title":"A novel chemometric method for the prediction of human oral bioavailability","volume":"13","author":"Xu","year":"2012","journal-title":"Int J Mol Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3949","DOI":"10.3390\/nu15183949","article-title":"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","volume":"15","author":"Elkhalifa","year":"2023","journal-title":"Nutrients"},{"key":"B18","doi-asserted-by":"publisher","first-page":"979","DOI":"10.3390\/plants10050979","article-title":"Deciphering the molecular mechanism responsible for efficiently inhibiting metastasis of human non-small cell lung and colorectal cancer cells targeting the matrix metalloproteinases by selaginella repanda","volume":"10","author":"Adnan","year":"2021","journal-title":"Plants"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.3390\/antiox11122491","article-title":"Antioxidant activities of natural polysaccharides and their derivatives for biomedical and medicinal applications","volume":"11","author":"Bai","year":"2022","journal-title":"Antioxidants"},{"key":"B20","doi-asserted-by":"publisher","first-page":"117768","DOI":"10.1016\/j.biopha.2024.117768","article-title":"Flavonoids and other constituents from Jacaranda mimosifolia: In vitro analysis, molecular docking, and molecular dynamic simulations of antioxidant and anti-inflammatory activities","volume":"182","author":"Leutcha","year":"2025","journal-title":"Biomed Pharmaco"},{"key":"B21","doi-asserted-by":"publisher","first-page":"102177","DOI":"10.1016\/j.fochx.2025.102177","article-title":"Preparation of flavonoids from Amomum tsaoko and evaluation of their antioxidant and \u03b1-glucosidase inhibitory activities","volume":"25","author":"Huang","year":"2025","journal-title":"FOCHX"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.092684","article-title":"The dual actions of morin (3, 5, 7, 2\u2019, 4-pentahydroxyflavone) as a hypouricemic agent: Uricosuric effect and xanthine oxidase inhibitory activity","volume":"316","author":"Yu","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.878726","article-title":"A bibliometric analysis of triptolide and the recent advances in treating non-small cell lung cancer","volume":"28","author":"Yang","year":"2018","journal-title":"Front Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-009-0853-2","article-title":"Associations of MDM2 SNP309, transcriptional activity, mRNA expression, and survival in stage I non-small-cell lung cancer patients with wild-type p53 tumors","volume":"17","author":"Chien","year":"2010","journal-title":"Ann Surg Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2022.26.6.511","article-title":"Neogambogic acid relieves myocardial injury induced by sepsis via p38 MAPK\/NF-\u03baB pathway","volume":"26","author":"Fu","year":"2022","journal-title":"Korean J Physiol Pharmacol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"113897","DOI":"10.1016\/j.biopha.2022.113897","article-title":"Systemic pharmacological verification of Salvia miltiorrhiza-Ginseng Chinese herb pair in inhibiting spontaneous breast cancer metastasis","volume":"26","author":"Han","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.06.146","article-title":"Downregulation of lncRNA ADAMTS9-AS2 contributes to gastric cancer development via activation of PI3K\/Akt pathway","volume":"107","author":"Cao","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2018.4371","article-title":"Circular RNA circCDK13 suppresses cell proliferation,migration and invasion by modulating the JAK\/STAT and PI3K\/Akt pathways in liver cancer","volume":"53","author":"Lin","year":"2018","journal-title":"Int J Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.08.119","article-title":"F-box and leucine-rich repeat protein 5 promotes colon cancer progression by modulating PTEN\/PI3K\/Akt signaling pathway","volume":"107","author":"Yao","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-013-1535-z","article-title":"Effects of AFP-activated PI3K\/Akt signaling pathway on cell proliferation of liver cancer","volume":"35","author":"Zheng","year":"2014","journal-title":"Tumor Biol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"599","DOI":"10.3892\/or.2018.6469","article-title":"Girdin regulates the proliferation and apoptosis of pancreatic cancer cells via the PI3K\/Akt signaling pathway","volume":"40","author":"Wang","year":"2018","journal-title":"Oncol Rep"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2972","DOI":"10.3390\/cancers12102972","article-title":"Therapeutic potential of PI3K\/AKT\/mTOR pathway in gastrointestinal stromal tumors: rationale and progress","volume":"12","author":"Duan","year":"2020","journal-title":"Cancers"},{"key":"B33","article-title":"Effect of PI3K-Akt signaling pathways on human Hct-8\/FU drug- resistant cell P-GP expression and drug resistant","volume":"32","author":"Zhang","year":"2013","journal-title":"J South Univer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.19852\/j.cnki.jtcm.20220408.003","article-title":"Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review","volume":"42","author":"Wu","year":"2022","journal-title":"JTCM"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1587856\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T05:24:47Z","timestamp":1748496287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1587856\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":34,"alternative-id":["10.3389\/fonc.2025.1587856"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1587856","relation":{},"ISSN":["2234-943X"],"issn-type":[{"type":"electronic","value":"2234-943X"}],"subject":[],"published":{"date-parts":[[2025,5,29]]},"article-number":"1587856"}}