{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:09:48Z","timestamp":1790881788774,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["01ZX2205B"],"award-info":[{"award-number":["01ZX2205B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lung cancer remains the leading cause of cancer-related mortality worldwide, with significant resistance to conventional therapies, highlighting the urgent need for novel therapeutic strategies. Moringa oleifera (M. oleifera), a medicinal plant rich in diverse bioactive compounds, has shown promising potential for anti-lung carcinoma activity. This study investigates the molecular mechanisms underlying the therapeutic effects of M. oleifera bioactive compounds for their anti-lung cancer activities through an integrated network modeling and molecular docking approach. By constructing comprehensive compound\u2013target\u2013lung cancer pathway networks, we aim to elucidate the multitarget pharmacology of M. oleifera compounds, providing valuable insights into their potential as therapeutic candidates. Computational pipeline was applied to identify 180 phytochemicals from M. oleifera, filtered using Lipinski\u2019s Rule of Five and ADMET properties, resulting in 10 lead compounds followed by their potential biological target proteins in regulating lung cancer progression. We identified 80 targeted proteins involved in lung cancer, with EGFR being the most enriched in pathway enrichment analysis. In the molecular docking analysis, caffeic acid showed the highest binding score (\u221228.97 kcal\/mol) with EGFR forming stable complex during molecular dynamics simulations compared to the known EGFR inhibitor \u2018erlotinib\u2019. The overall results suggest that caffeic acid, a key bioactive compound in M. oleifera, is an EGFR-mediated oncogenic signaling inhibitor for lung cancer therapy, warranting further experimental validation to translate these findings into clinical applications.<\/jats:p>","DOI":"10.3390\/ijms262010191","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:27:29Z","timestamp":1760963249000},"page":"10191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Therapeutic Potential of Moringa oleifera Against Lung Cancer Through Network Modeling and Molecular Docking Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3406-7587","authenticated-orcid":false,"given":"Anuj","family":"Singh","sequence":"first","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University, Lucknow 226028, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Ohri","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University, Lucknow 226028, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6105-2937","authenticated-orcid":false,"given":"Olaf","family":"Wolkenhauer","sequence":"additional","affiliation":[{"name":"Department of Systems Biology & Bioinformatics, University of Rostock, 18051 Rostock, Germany"},{"name":"Department of Biomedical Engineering & Bioinformatics, Chhattisgarh Swami Vivekananda Technical University, Bhilai 491107, India"},{"name":"Leibniz Institute for Food Systems Biology, Technical University of Munich, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen Kumar","family":"Gautam","sequence":"additional","affiliation":[{"name":"Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-3260","authenticated-orcid":false,"given":"Shailendra","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Systems Biology & Bioinformatics, University of Rostock, 18051 Rostock, Germany"},{"name":"Department of Biomedical Engineering & Bioinformatics, Chhattisgarh Swami Vivekananda Technical University, Bhilai 491107, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8789-615X","authenticated-orcid":false,"given":"Krishna P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Systems Biology & Bioinformatics, University of Rostock, 18051 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"45","article-title":"Epidemiology of lung cancer","volume":"25","author":"Thandra","year":"2021","journal-title":"Contemp. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccm.2019.10.001","article-title":"Lung Cancer 2020: Epidemiology, Etiology, and Prevention","volume":"41","author":"Bade","year":"2020","journal-title":"Clin. Chest Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.pulmoe.2020.02.005","article-title":"Conquering lung cancer: Current status and prospects for the future","volume":"26","author":"Pirker","year":"2020","journal-title":"Pulmonology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1053\/j.seminoncol.2022.06.013","article-title":"Impact of CT screening in lung cancer: Scientific evidence and literature review","volume":"49","author":"Kennedy","year":"2022","journal-title":"Semin. Oncol."},{"key":"ref_6","first-page":"1","article-title":"Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives","volume":"6","author":"Zhong","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1177\/2156587217696927","article-title":"Effective Medicinal Plant in Cancer Treatment, Part 2: Review Study","volume":"22","author":"Kooti","year":"2017","journal-title":"J. Evid.-Based Complement. Altern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dehelean, C.A., Marcovici, I., Soica, C., Mioc, M., Coricovac, D., Iurciuc, S., Cretu, O.M., and Pinzaru, I. (2021). Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy. Molecules, 26.","DOI":"10.3390\/molecules26041109"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Siddiqui, A.J., Jahan, S., Singh, R., Saxena, J., Ashraf, S.A., Khan, A., Choudhary, R.K., Balakrishnan, S., Badraoui, R., and Bardakci, F. (2022). Plants in Anticancer Drug Discovery: From Molecular Mechanism to Chemoprevention. BioMed Res. Int., 2022.","DOI":"10.1155\/2022\/5425485"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"184","DOI":"10.3390\/ddc3010011","article-title":"Plant-Derived Natural Products: A Source for Drug Discovery and Development","volume":"3","author":"Sezer","year":"2024","journal-title":"Drugs Drug Candidates"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1093\/ndt\/gfad208","article-title":"Natural product drug discovery and drug design: Two approaches shaping new pharmaceutical development","volume":"39","author":"Tzvetkov","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/ptr.2023","article-title":"Moringa oleifera: A food plant with multiple medicinal uses","volume":"21","author":"Anwar","year":"2007","journal-title":"Phyther. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s10722-010-9629-6","article-title":"\u201cDrumstick tree\u201d (Moringa oleifera Lam.): A multipurpose potential species in India","volume":"58","author":"Pandey","year":"2011","journal-title":"Genet. Resour. Crop Evol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6627265","DOI":"10.1155\/2021\/6627265","article-title":"Moringa oleifera is a Prominent Source of Nutrients with Potential Health Benefits","volume":"2021","author":"Islam","year":"2021","journal-title":"Int. J. Food Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S2221-1691(13)60126-4","article-title":"Estimation of total phenolic content, in\u2013vitro antioxidant and anti\u2013inflammatory activity of flowers of Moringa oleifera","volume":"3","author":"Alhakmani","year":"2013","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.livsci.2014.01.001","article-title":"Effect of Moringa oleifera leaf meal on growth performance, apparent digestibility, digestive organ size and carcass yield in broiler chickens","volume":"161","author":"Nkukwana","year":"2014","journal-title":"Livest. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kashyap, P., Kumar, S., Riar, C.S., Jindal, N., Baniwal, P., Guin\u00e9, R.P.F., Correia, P.M.R., Mehra, R., and Kumar, H. (2022). Recent Advances in Drumstick (Moringa oleifera) Leaves Bioactive Compounds: Composition, Health Benefits, Bioaccessibility, and Dietary Applications. Antioxidants, 11.","DOI":"10.3390\/antiox11020402"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.biopha.2018.09.060","article-title":"Moringa oleifera and their phytonanoparticles: Potential antiproliferative agents against cancer","volume":"108","author":"Tiloke","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s43088-021-00101-2","article-title":"Anticancer activities of phenolic compounds from Moringa oleifera leaves: In vitro and in silico mechanistic study","volume":"10","author":"Mumtaz","year":"2021","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wu, Y.-Y., Xu, Y.-M., Y Lau, A.T., Ferreira de Oliveira, P., Ribeiro, D., Ascenso, A., and Santos, C. (2021). Anti-Cancer and Medicinal Potentials of Moringa Isothiocyanate. Molecules, 26.","DOI":"10.3390\/molecules26247512"},{"key":"ref_22","first-page":"1483","article-title":"Moringa oleifera: Antioxidant, Anticancer, Anti-inflammatory, and Related Properties of Extracts in Cell Lines: A Review of Medicinal Effects, Phytochemistry, and Applications","volume":"22","author":"Ramamurthy","year":"2021","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/fft2.181","article-title":"Role of Moringa oleifera Lam. in cancer: Phytochemistry and pharmacological insights","volume":"4","author":"Singh","year":"2023","journal-title":"Food Front."},{"key":"ref_24","first-page":"2141","article-title":"Moringa oleifera Root Induces Cancer Apoptosis more Effectively than Leave Nanocomposites and Its Free Counterpart","volume":"18","author":"Abdalla","year":"2017","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bhadresha, K., Thakore, V., Brahmbhatt, J., Upadhyay, V., Jain, N., and Rawal, R. (2022). Anticancer effect of Moringa oleifera leaves extract against lung cancer cell line via induction of apoptosis. Adv. Cancer Biol.\u2014Metastasis, 6.","DOI":"10.1016\/j.adcanc.2022.100072"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5591687","DOI":"10.1155\/2021\/5591687","article-title":"Alkaloid Extract of Moringa oleifera Lam. Exerts Antitumor Activity in Human Non-Small-Cell Lung Cancer via Modulation of the JAK2\/STAT3 Signaling Pathway","volume":"2021","author":"Xie","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ji, H., Li, K., Xu, W., Li, R., Xie, S., and Zhu, X. (2022). Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Network Pharmacology Study and Experimental Validation. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.780387"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1021\/acsomega.3c05589","article-title":"Integrated Network Pharmacology Approach to Evaluate Bioactive Phytochemicals of Acalypha indica and Their Mechanistic Actions to Suppress Target Genes of Tuberculosis","volume":"9","author":"Harakeh","year":"2024","journal-title":"ACS Omega"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s13020-023-00853-2","article-title":"Network Pharmacology: A Bright Guiding Light on the Way to Explore the Personalized Precise Medication of Traditional Chinese Medicine","volume":"18","author":"Li","year":"2023","journal-title":"Chin. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mohanraj, K., Karthikeyan, B.S., Vivek-Ananth, R.P., Chand, R.P.B., Aparna, S.R., Mangalapandi, P., and Samal, A. (2018). IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry and Therapeutics. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22631-z"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lans, C., and van Asseldonk, T. (2020). Dr. Duke\u2019s Phytochemical and Ethnobotanical Databases, a Cornerstone in the Validation of Ethnoveterinary Medicinal Plants, as Demonstrated by Data on Pets in British Columbia. Medicinal and Aromatic Plants of North America, Springer.","DOI":"10.1007\/978-3-030-44930-8_10"},{"key":"ref_32","unstructured":"Ali, M. (2019, January 26). PCIDB\u2014PhytoChemical Interactions DataBase. Proceedings of the Training Workshop: Metabolic Engineering for Primary and Secondary Compounds Production from Medicinal, Aromatic and Economical Plants, Cairo, Egypt."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6001","DOI":"10.2147\/IJGM.S325398","article-title":"Poisoning of Butanol-Containing Products: Clinical Characteristics and Outcomes","volume":"14","author":"Trakulsrichai","year":"2021","journal-title":"Int. J. Gen. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0300-483X(88)90144-8","article-title":"Role of benzylamine oxidase in the cytotoxicity of allylamine toward aortic smooth muscle cells","volume":"51","author":"Hysmith","year":"1988","journal-title":"Toxicology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/j.fct.2004.03.014","article-title":"Subacute (28-day) toxicity of furfural in Fischer 344 rats: A comparison of the oral and inhalation route","volume":"42","author":"Arts","year":"2004","journal-title":"Food Chem. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.forsciint.2004.09.112","article-title":"Fatal workplace accident involving ethyl acetate: A distribution study","volume":"154","author":"Coopman","year":"2005","journal-title":"Forensic Sci. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2021\/9255305","article-title":"Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets of Astragalus Radix-Panax notoginseng Herb Pair on Treating Diabetic Nephropathy","volume":"2021","author":"Zhao","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yuan, Y., Wang, W., He, Y., Zhong, H., Zhou, X., Chen, Y., Cai, X.J., and Liu, L.Q. (2022). Mechanisms underlying the therapeutic effects of Qingfeiyin in treating acute lung injury based on GEO datasets, network pharmacology and molecular docking. Comput. Biol. Med., 145.","DOI":"10.1016\/j.compbiomed.2022.105454"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rah, B., Rather, R.A., Bhat, G.R., Baba, A.B., Mushtaq, I., Farooq, M., Yousuf, T., Dar, S.B., Parveen, S., and Hassan, R. (2022). JAK\/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.821344"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ebrahimnezhad, M., Natami, M., Bakhtiari, G.H., Tabnak, P., Ebrahimnezhad, N., Yousefi, B., and Majidinia, M. (2023). FOXO1, a tiny protein with intricate interactions: Promising therapeutic candidate in lung cancer. Biomed. Pharmacother., 169.","DOI":"10.1016\/j.biopha.2023.115900"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"793","DOI":"10.4155\/fmc-2018-0468","article-title":"MAPK Pathway: A Potential Target for the Treatment of Non-small-cell Lung Carcinoma","volume":"11","author":"Pradhan","year":"2019","journal-title":"Future Med. Chem."},{"key":"ref_42","first-page":"1","article-title":"Targeting the RAS\/RAF\/MAPK pathway for cancer therapy: From mechanism to clinical studies","volume":"8","author":"Bahar","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.trsl.2020.12.009","article-title":"Potentially functional variants of HBEGF and ITPR3 in GnRH signaling pathway genes predict survival of non-small cell lung cancer patients","volume":"233","author":"Wu","year":"2021","journal-title":"Transl. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101364","DOI":"10.1016\/j.tranon.2022.101364","article-title":"The PI3K\/Akt\/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles","volume":"18","author":"Sanaei","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_45","first-page":"724","article-title":"erbB in NSCLC as a molecular target: Current evidences and future directions","volume":"5","author":"Cucchiara","year":"2020","journal-title":"ESMO Open"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.gendis.2023.02.039","article-title":"HIF-1\u03b1 signaling: Essential roles in tumorigenesis and implications in targeted therapies","volume":"11","author":"Zhao","year":"2023","journal-title":"Genes Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"90","DOI":"10.20892\/j.issn.2095-3941.2016.0086","article-title":"Roles of Rap1 signaling in tumor cell migration and invasion","volume":"14","author":"Zhang","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Cui, J.W., Li, Y., Yang, Y., Yang, H.K., Dong, J.M., Xiao, Z.H., He, X., Guo, J.H., Wang, R.Q., and Dai, B. (2024). Tumor immunotherapy resistance: Revealing the mechanism of PD-1\/PD-L1-mediated tumor immune escape. Biomed. Pharmacother., 171.","DOI":"10.1016\/j.biopha.2024.116203"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s12935-024-03525-9","article-title":"Th17 cell function in cancers: Immunosuppressive agents or anti-tumor allies?","volume":"24","author":"Anvar","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100113","DOI":"10.1016\/j.medidd.2021.100113","article-title":"Wnt\/\u03b2-catenin signaling pathway in lung cancer","volume":"13","author":"Zhu","year":"2022","journal-title":"Med. Drug Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1093\/carcin\/bgm130","article-title":"Caffeic Acid and Its Synthetic Derivative CADPE Suppress Tumor Angiogenesis by Blocking STAT3-Mediated VEGF Expression in Human Renal Carcinoma Cells","volume":"28","author":"Jung","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7269","DOI":"10.3390\/molecules19067269","article-title":"Synthesis of Caffeic Acid Amides Bearing 2,3,4,5-Tetrahydrobenzo[b][1,4]dioxocine Moieties and Their Biological Evaluation as Antitumor Agents","volume":"19","author":"Yuan","year":"2014","journal-title":"Molecules"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Villota, H., Santa-Gonz\u00e1lez, G.A., Uribe, D., Henao, I.C., Arroyave-Ospina, J.C., Barrera-Causil, C.J., and Pedroza-D\u00edaz, J. (2022). Modulatory Effect of Chlorogenic Acid and Coffee Extracts on Wnt\/\u03b2-Catenin Pathway in Colorectal Cancer Cells. Nutrients, 14.","DOI":"10.3390\/nu14224880"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.31254\/phyto.2024.13103","article-title":"Identification of Hsp90 Inhibitors from Ananas comosus Potential Phytochemicals for Lung Cancer Treatment","volume":"13","author":"Alam","year":"2024","journal-title":"J. Phytopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e32623","DOI":"10.1016\/j.heliyon.2024.e32623","article-title":"Caffeic Acid and Diabetic Neuropathy: Investigating Protective Effects and Insulin-Like Growth Factor 1 (IGF-1)-Related Antioxidative and Anti-Inflammatory Mechanisms in Mice","volume":"10","author":"Hou","year":"2024","journal-title":"Heliyon"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1291\/hypres.28.369","article-title":"Caffeic Acid Inhibits Vascular Smooth Muscle Cell Proliferation Induced by Angiotensin II in Stroke-Prone Spontaneously Hypertensive Rats","volume":"28","author":"Li","year":"2005","journal-title":"Hypertens. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/carcin\/bgn282","article-title":"Caffeic Acid, a Phenolic Phytochemical in Coffee, Directly Inhibits Fyn Kinase Activity and UVB-Induced COX-2 Expression","volume":"30","author":"Kang","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ram\u00edrez, D., and Caballero, J. (2018). Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?. Molecules, 23.","DOI":"10.3390\/molecules23051038"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"509","DOI":"10.4103\/1735-5362.245963","article-title":"Exploring the interaction between epidermal growth factor receptor tyrosine kinase and some of the synthesized inhibitors using combination of in-silico and in-vitro cytotoxicity methods","volume":"13","author":"Nasab","year":"2018","journal-title":"Res. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1073\/pnas.0709662105","article-title":"The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP","volume":"105","author":"Yun","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7545","DOI":"10.1080\/07391102.2021.1900917","article-title":"Molecular interaction study of novel indoline derivatives with EGFR-kinase domain using multiple computational analysis","volume":"40","author":"Palanivel","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cell.2009.04.025","article-title":"Mechanism for activation of the EGF receptor catalytic domain by the juxtamembrane segment","volume":"137","author":"Jura","year":"2009","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Martin-Fernandez, M.L., Clarke, D.T., Roberts, S.K., Zanetti-Domingues, L.C., and Gervasio, F.L. (2019). Structure and Dynamics of the EGF Receptor as Revealed by Experiments and Simulations and Its Relevance to Non-Small Cell Lung Cancer. Cells, 8.","DOI":"10.3390\/cells8040316"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6203","DOI":"10.1080\/07391102.2022.2104375","article-title":"Molecular dynamics simulations reveal the inhibitory mechanism of Withanolide A against \u03b1-glucosidase and \u03b1-amylase","volume":"41","author":"Oyewusi","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Singh, K.P., Singh, A., Wolkenhauer, O., and Gupta, S.K. (2024). Regulatory Role of IL6 in Immune-Related Adverse Events during Checkpoint Inhibitor Treatment in Melanoma. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202409.0006.v1"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Yang, Y.A., Tang, W.J., Zhang, X., Yuan, J.W., Liu, X.H., and Zhu, H.L. (2014). Synthesis, Molecular Docking and Biological Evaluation of Glycyrrhizin Analogs as Anticancer Agents Targeting EGFR. Molecules, 19.","DOI":"10.3390\/molecules19056368"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1021\/jm400072p","article-title":"Protein kinase inhibitor design by targeting the Asp-Phe-Gly (DFG) motif: The role of the DFG motif in the design of epidermal growth factor receptor inhibitors","volume":"56","author":"Peng","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Vicidomini, G. (2023). Current Challenges and Future Advances in Lung Cancer: Genetics, Instrumental Diagnosis and Treatment. Cancers, 15.","DOI":"10.3390\/cancers15143710"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s13237-022-00405-3","article-title":"Plant-derived natural products for drug discovery: Current approaches and prospects","volume":"65","author":"Nasim","year":"2022","journal-title":"Nucleus"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1526-4637.2007.00300.x","article-title":"Analgesic efficacy and safety of morphine-chitosan nasal solution in patients with moderate to severe pain following orthopedic surgery","volume":"9","author":"Stoker","year":"2008","journal-title":"Pain Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"14","DOI":"10.2174\/157489208783478685","article-title":"Development of Taxol and Other Endophyte Produced Anti-Cancer Agents","volume":"3","author":"Sze","year":"2008","journal-title":"Recent Pat. Anticancer Drug Discov."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Rai, V., Tandon, P.K., and Khatoon, S. (2014). Effect of Chromium on Antioxidant Potential of Catharanthus roseus Varieties and Production of Their Anticancer Alkaloids: Vincristine and Vinblastine. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/934182"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Liang, X., Wang, P., Yang, C., Huang, F., Wu, H., Shi, H., and Wu, X. (2021). Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.646628"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yao, C., Dai, S., Wang, C., Fu, K., Wu, R., Zhao, X., Yao, Y., and Li, Y. (2023). Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115464"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Li, W., Yuan, G., Pan, Y., Wang, C., and Chen, H. (2017). Network Pharmacology Studies on the Bioactive Compounds and Action Mechanisms of Natural Products for the Treatment of Diabetes Mellitus: A Review. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00074"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"104206","DOI":"10.1016\/j.arabjc.2022.104206","article-title":"Moringa oleifera Leaves from Brazil: Influence of Seasonality, Regrowth Age, and Region on Biochemical Markers and Antioxidant Potential","volume":"15","author":"Oldoni","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"117372","DOI":"10.1016\/j.indcrop.2023.117372","article-title":"Extraction, Purification, and Applications of Vanillin: A Review of Recent Advances and Challenges","volume":"204","author":"Liaqat","year":"2023","journal-title":"Ind. Crops Prod."},{"key":"ref_78","first-page":"7","article-title":"Isolation and Structure Elucidation of Moringyne, a New Glycoside from Seeds of Moringa oleifera","volume":"28","author":"Memon","year":"1985","journal-title":"Pak. J. Sci. Ind. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.biortech.2005.11.003","article-title":"Anti-Fungal Activity of Crude Extracts and Essential Oil of Moringa oleifera Lam","volume":"98","author":"Chuang","year":"2007","journal-title":"Bioresour. Technol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Cirlini, M., Del Vecchio, L., Leto, L., Russo, F., Dellafiora, L., Guarrasi, V., and Chiancone, B. (2022). Sprouts of Moringa oleifera Lam.: Germination, Polyphenol Content and Antioxidant Activity. Molecules, 27.","DOI":"10.3390\/molecules27248774"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Uribe, M.L., Marrocco, I., and Yarden, Y. (2021). EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance. Cancers, 13.","DOI":"10.3390\/cancers13112748"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.semcancer.2019.09.015","article-title":"Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer","volume":"61","author":"Harrison","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Kim, M.K., Yee, J., Cho, Y.S., Jang, H.W., Han, J.M., and Gwak, H.S. (2018). Risk factors for erlotinib-induced hepatotoxicity: A retrospective follow-up study. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4891-7"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"154860","DOI":"10.1016\/j.phymed.2023.154860","article-title":"Caffeic acid phenethyl ester suppresses EGFR\/FAK\/Akt signaling, migration, and tumor growth of prostate cancer cells","volume":"116","author":"Tseng","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jnutbio.2018.02.016","article-title":"Caffeic acid phenethyl ester down-regulates claudin-2 expression at the transcriptional and post-translational levels and enhances chemosensitivity to doxorubicin in lung adenocarcinoma A549 cells","volume":"56","author":"Sonoki","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jab.2015.05.001","article-title":"Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells","volume":"13","author":"Mudjupa","year":"2015","journal-title":"J. Appl. Biomed."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0973-6883(11)60112-6","article-title":"Erlotinib-induced hepatotoxicity-clinical presentation and successful management: A case report","volume":"1","author":"Arora","year":"2011","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Liang, W., Wu, X., Fang, W., Zhao, Y., Yang, Y., Hu, Z., Xue, C., Zhang, J., Zhang, J., and Ma, Y. (2014). Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients with advanced non-small-cell lung cancer harboring EGFR mutations. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085245"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3106363","DOI":"10.1155\/2022\/3106363","article-title":"Virtual Screening and Network Pharmacology-Based Study to Explore the Pharmacological Mechanism of Clerodendrum Species for Anticancer Treatment","volume":"2022","author":"Gogoi","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.ddtec.2004.11.007","article-title":"Lead- and drug-like compounds: The rule-of-five revolution","volume":"1","author":"Lipinski","year":"2004","journal-title":"Drug Discov. Today Technol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1039\/C8MD00472B","article-title":"ADMET-score\u2014A comprehensive scoring function for evaluation of chemical drug-likeness","volume":"10","author":"Guan","year":"2019","journal-title":"Medchemcomm"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"W32","DOI":"10.1093\/nar\/gku293","article-title":"SwissTargetPrediction: A web server for target prediction of bioactive small molecules","volume":"42","author":"Gfeller","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_93","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Ronzano","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"115751","DOI":"10.1016\/j.jep.2022.115751","article-title":"Uncovering the molecular mechanisms of Curcumae Rhizoma against myocardial fibrosis using network pharmacology and experimental validation","volume":"300","author":"Zhang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Liu, J., Meng, J., Li, R., Jiang, H., Fu, L., Xu, T., Zhu, G.Y., Zhang, W., Gao, J., and Jiang, Z.H. (2022). Integrated network pharmacology analysis, molecular docking, LC-MS analysis and bioassays revealed the potential active ingredients and underlying mechanism of Scutellariae radix for COVID-19. Front. Plant Sci., 13.","DOI":"10.3389\/fpls.2022.988655"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1021\/ci800081s","article-title":"Fully automated molecular mechanics based induced fit protein\u2014Ligand docking method","volume":"48","author":"Koska","year":"2008","journal-title":"J. Chem. Inf. Model."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"71","DOI":"10.21037\/atm-21-6967","article-title":"Homology modeling and molecular docking simulation of martentoxin as a specific inhibitor of the BK channel","volume":"10","author":"Yang","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1021\/ct300400x","article-title":"Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone \u03c6, \u03c8 and side-chain \u03c71 and \u03c72 Dihedral Angles","volume":"8","author":"Best","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"9620","DOI":"10.7150\/thno.44176","article-title":"LncRNA-SLC16A1-AS1 induces metabolic reprogramming during Bladder Cancer progression as target and co-activator of E2F1","volume":"10","author":"Logotheti","year":"2020","journal-title":"Theranostics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10191\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:44:42Z","timestamp":1761054282000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":103,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010191"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010191","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]}}}