{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:34:07Z","timestamp":1793345647284,"version":"4.5.0"},"reference-count":178,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The BCR-ABL fusion oncoprotein, a constitutively active tyrosine kinase, plays a central role in the pathogenesis of chronic myeloid leukemia (CML). While tyrosine kinase inhibitors (TKIs) have transformed CML treatment, issues such as drug resistance, particularly involving mutations like T315I, and adverse effects underscore the need for alternative or complementary therapeutic strategies. Natural products derived from plants have long served as a reservoir for anticancer agents, offering structural diversity and multi-targeted bioactivity. Notably, many plant-based compounds exhibit anticancer effects with comparatively lower toxicity and fewer side effects than synthetic TKIs, making them attractive candidates for safer long-term use. This review explores the recent advances in plant-based natural compounds that directly or indirectly inhibit BCR-ABL kinase activity and its downstream signaling pathways. Key compounds are discussed with respect to their mechanisms of action, structure\u2013activity relationships, and potential to overcome TKI resistance. Several of these compounds directly target BCR-ABL or promote its degradation, while others inhibit downstream effectors such as STAT5 and PI3K\/Akt, leading to apoptosis and growth inhibition of leukemic cells. The synergistic potential of these natural products with existing TKIs and their promise to target drug-resistant CML cells further highlight their translational value. By integrating insights from molecular pharmacology, medicinal chemistry, and leukemia biology, this review supports the continued investigation of plant-derived agents as novel or adjunctive therapies against BCR-ABL-driven leukemias.<\/jats:p>","DOI":"10.3390\/molecules30214160","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T02:03:48Z","timestamp":1761185028000},"page":"4160","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Natural Products Targeting BCR-ABL: A Plant-Based Approach to Chronic Myeloid Leukemia Treatment"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3003-9497","authenticated-orcid":false,"given":"Louisa","family":"Pechlivani","sequence":"first","affiliation":[{"name":"Neurosurgical Institute, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-9979","authenticated-orcid":false,"given":"Alexandros","family":"Giannakis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2184-4945","authenticated-orcid":false,"given":"Chrissa","family":"Sioka","sequence":"additional","affiliation":[{"name":"Neurosurgical Institute, University of Ioannina, 45500 Ioannina, Greece"},{"name":"Nuclear Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0257-4481","authenticated-orcid":false,"given":"Georgios A.","family":"Alexiou","sequence":"additional","affiliation":[{"name":"Neurosurgical Institute, University of Ioannina, 45500 Ioannina, Greece"},{"name":"Department of Neurosurgery, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-1024","authenticated-orcid":false,"given":"Athanassios P.","family":"Kyritsis","sequence":"additional","affiliation":[{"name":"Neurosurgical Institute, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1001\/jama.2025.0220","article-title":"Chronic Myeloid Leukemia","volume":"333","author":"Jabbour","year":"2025","journal-title":"JAMA"},{"key":"ref_2","unstructured":"Eden, R.E., and Coviello, J.M. (2025, September 04). Chronic Myelogenous Leukemia, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK531459."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s13045-018-0624-2","article-title":"Past, Present, and Future of Bcr-Abl Inhibitors: From Chemical Development to Clinical Efficacy","volume":"11","author":"Rossari","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pechlivani, L., Ntemou, N., Pantazi, D., Alivertis, D., Skobridis, K., and Tselepis, A.D. (2024). Synthesis of Novel Nilotinib Analogues and Biological Evaluation of Their Antiplatelet Activity and Functionality towards Cancer Cell Proliferation In Vitro. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030349"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s43046-025-00263-5","article-title":"Current and Future of Targeted Therapies against BCR::ABL Kinases","volume":"37","author":"Jayavel","year":"2025","journal-title":"J. Egypt. Natl. Cancer Inst."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cytogfr.2025.05.001","article-title":"BCR-ABL: The Molecular Mastermind behind Chronic Myeloid Leukemia","volume":"83","author":"Shammas","year":"2025","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/ajh.27443","article-title":"Chronic Myeloid Leukemia: 2025 Update on Diagnosis, Therapy, and Monitoring","volume":"99","author":"Jabbour","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1080\/17474086.2021.1990034","article-title":"Novel BCR-ABL1 Tyrosine Kinase Inhibitors in the Treatment of Chronic Myeloid Leukemia","volume":"14","author":"Malik","year":"2021","journal-title":"Expert Rev. Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/14740338.2024.2331190","article-title":"A Safety Review of Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia","volume":"23","year":"2024","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Jurkovicova, D., Neophytou, C.M., Ga\u0161parovi\u0107, A.\u010c., and Gon\u00e7alves, A.C. (2022). DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314672"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, R., Sun, Y., Li, C., Xue, Y., and Ba, X. (2023). Targeting the DNA Damage Response for Cancer Therapy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115907"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"155161","DOI":"10.1016\/j.prp.2024.155161","article-title":"The Impact of the BCR-ABL Oncogene in the Pathology and Treatment of Chronic Myeloid Leukemia","volume":"254","author":"Nsairat","year":"2024","journal-title":"Pathol.-Res. Pract."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.hoc.2017.04.007","article-title":"Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Kinase Inhibitors","volume":"31","author":"Patel","year":"2017","journal-title":"Hematol.\/Oncol. Clin. N. Am."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s40291-016-0208-1","article-title":"Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy","volume":"20","author":"Ali","year":"2016","journal-title":"Mol. Diagn. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bavaro, L., Martelli, M., Cavo, M., and Soverini, S. (2019). Mechanisms of Disease Progression and Resistance to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: An Update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20246141"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7374","DOI":"10.1158\/1078-0432.CCR-06-1516","article-title":"Contribution of ABL Kinase Domain Mutations to Imatinib Resistance in Different Subsets of Philadelphia-Positive Patients: By the GIMEMA Working Party on Chronic Myeloid Leukemia","volume":"12","author":"Soverini","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_17","first-page":"412","article-title":"T315I\u2014A Gatekeeper Point Mutation and Its Impact on the Prognosis of Chronic Myeloid Leukemia","volume":"5","author":"Kaleem","year":"2024","journal-title":"Adv. Lab. Med.\/Av. Med. Lab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.21873\/anticanres.14215","article-title":"ABL1-Directed Inhibitors for CML: Efficacy, Resistance and Future Perspectives","volume":"40","author":"Massimino","year":"2020","journal-title":"Anticancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mandal\u00e0, M., and Romano, E. (2018). Mechanisms of Drug Resistance in Cancer Therapy, Springer.","DOI":"10.1007\/978-3-030-10507-5"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2120165","DOI":"10.1001\/jamanetworkopen.2021.20165","article-title":"Comparison of Hepatotoxicity Associated With New BCR-ABL Tyrosine Kinase Inhibitors vs Imatinib Among Patients With Chronic Myeloid Leukemia","volume":"4","author":"Wang","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yu, Z., Lei, Z., Yao, X., Wang, H., Zhang, M., Hou, Z., Li, Y., Zhao, Y., Li, H., and Liu, D. (2022). Potential Drug-Drug Interaction of Olverembatinib (HQP1351) Using Physiologically Based Pharmacokinetic Models. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1065130"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e35832","DOI":"10.1002\/cncr.35832","article-title":"Olverembatinib in Chronic Myeloid Leukemia\u2014Review of Historical Development, Current Status, and Future Research","volume":"131","author":"Kantarjian","year":"2025","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13045-022-01334-z","article-title":"Olverembatinib (HQP1351), a Well-Tolerated and Effective Tyrosine Kinase Inhibitor for Patients with T315I-Mutated Chronic Myeloid Leukemia: Results of an Open-Label, Multicenter Phase 1\/2 Trial","volume":"15","author":"Jiang","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1182\/blood-2022-166452","article-title":"Efficacy and Safety of Vodobatinib in Patients (Pts) with Chronic Phase Philadelphia Positive Chronic Myeloid Leukemia (Ph+ CML): A Sub Group Analysis By Lines of Tyrosine Kinase Inhibitor (TKI) Therapy","volume":"140","author":"Cortes","year":"2022","journal-title":"Blood"},{"key":"ref_25","unstructured":"(2025, October 18). Vodobatinib, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Vodobatinib."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.1007\/s00277-025-06239-8","article-title":"Phase-1 Study of Vamotinib (PF-114), a 3rd Generation BCR::ABL1 Tyrosine Kinase-Inhibitor, in Chronic Myeloid Leukaemia","volume":"104","author":"Turkina","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_27","unstructured":"(2025, October 18). Vamotinib (PF-114), Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Vamotinib."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1007\/s40262-024-01428-6","article-title":"Clinical Pharmacology of Asciminib: A Review","volume":"63","author":"Hoch","year":"2024","journal-title":"Clin. Pharmacokinet."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhu, L.-X., Zhang, H.-Z., Zhang, C., and Zhou, C.-H. (2025). Comprehensive Insights into Emodin Compounds Research in Medicinal Chemistry. Bioorg. Med. Chem., 128.","DOI":"10.1016\/j.bmc.2025.118262"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Min, H., Niu, M., Zhang, W., Yan, J., Li, J., Tan, X., Li, B., Su, M., Di, B., and Yan, F. (2017). Emodin Reverses Leukemia Multidrug Resistance by Competitive Inhibition and Downregulation of P-Glycoprotein. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187971"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1177\/1534735416664784","article-title":"Emodin Exerts an Antiapoptotic Effect on Human Chronic Myelocytic Leukemia K562 Cell Lines by Targeting the PTEN\/PI3K-AKT Signaling Pathway and Deleting BCR-ABL","volume":"16","author":"Wang","year":"2017","journal-title":"Integr. Cancer Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00432-014-1820-2","article-title":"Inhibition of 32Dp210 Cells Harboring T315I Mutation by a Novel Derivative of Emodin Correlates with Down-Regulation of BCR-ABL and Its Downstream Signaling Pathways","volume":"141","author":"Li","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_33","first-page":"1","article-title":"Effect of A Novel Emodin Derivative on Chronic Myelogenous Leukemia K562 Cells and Imatinib-Resistant K562\/G01 Cells","volume":"24","author":"Li","year":"2016","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1248\/bpb.b20-00325","article-title":"Emodin Inhibits Resistance to Imatinib by Downregulation of Bcr-Abl and STAT5 and Allosteric Inhibition in Chronic Myeloid Leukemia Cells","volume":"43","author":"Wang","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_35","first-page":"260","article-title":"Emodin and AZT Synergistically Inhibit the Proliferation and Induce the Apoptosis of Leukemia K562 Cells through the EGR1 and the Wnt\/\u0392-catenin Pathway","volume":"43","author":"Ma","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhou, L., Hu, X., Han, C., Niu, X., Han, L., Yu, H., Pan, G., and Fu, Z. (2023). Comprehensive Investigation on the Metabolism of Emodin Both in Vivo and in Vitro. J. Pharm. Biomed. Anal., 223.","DOI":"10.1016\/j.jpba.2022.115122"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e33631","DOI":"10.1016\/j.heliyon.2024.e33631","article-title":"Advances in the Mechanism of Emodin-Induced Hepatotoxicity","volume":"10","author":"Wang","year":"2024","journal-title":"Heliyon"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1002\/ptr.5631","article-title":"Emodin: A Review of Its Pharmacology, Toxicity and Pharmacokinetics","volume":"30","author":"Dong","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1002\/fsn3.3986","article-title":"Oridonin from Rabdosia Rubescens: An Emerging Potential in Cancer Therapy\u2014A Comprehensive Review","volume":"12","author":"Ali","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Huang, H., Weng, H., Dong, B., Zhao, P., Zhou, H., and Qu, L. (2017). Oridonin Triggers Chaperon-Mediated Proteasomal Degradation of BCR-ABL in Leukemia. Sci. Rep., 7.","DOI":"10.1038\/srep41525"},{"key":"ref_41","first-page":"1378","article-title":"Anti-Leukemia Effect and Mechanism of Oridonin on Imatinib-Sensitive and Imatinib-Resistant K562 Cells","volume":"25","author":"Shan","year":"2017","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.gendis.2020.06.010","article-title":"Oridonin and Its Derivatives for Cancer Treatment and Overcoming Therapeutic Resistance","volume":"8","author":"Liu","year":"2021","journal-title":"Genes Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.4161\/cbt.21460","article-title":"Oridonin in Combination with Imatinib Exerts Synergetic Anti-Leukemia Effect in Ph+ Acute Lymphoblastic Leukemia Cells in Vitro by Inhibiting Activation of LYN\/MTOR Signaling Pathway","volume":"13","author":"Guo","year":"2012","journal-title":"Cancer Biol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.7150\/jca.83219","article-title":"Differentiation of Imatinib -Resistant Chronic Myeloid Leukemia Cells with BCR-ABL-T315I Mutation Induced by Jiyuan Oridonin A","volume":"14","author":"Xu","year":"2023","journal-title":"J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Xu, J., Wold, E., Ding, Y., Shen, Q., and Zhou, J. (2018). Therapeutic Potential of Oridonin and Its Analogs: From Anticancer and Antiinflammation to Neuroprotection. Molecules, 23.","DOI":"10.3390\/molecules23020474"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1111\/j.1745-7254.2006.00440.x","article-title":"Pharmacokinetic Behaviors and Oral Bioavailability of Oridonin in Rat Plasma","volume":"27","author":"Xu","year":"2006","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wang, S., Dai, M., Nai, J., Zhu, L., and Sheng, H. (2020). Solubility and Bioavailability Enhancement of Oridonin: A Review. Molecules, 25.","DOI":"10.3390\/molecules25020332"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Su, Y., Liu, L., Lin, C., Deng, D., Li, Y., Huang, M., Wang, Y., Ling, K., Wang, H., and Chen, Q. (2024). Enhancing Cancer Therapy: Advanced Nanovehicle Delivery Systems for Oridonin. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1476739"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3899","DOI":"10.1158\/1078-0432.CCR-20-0829","article-title":"\u201cAll Our Wisdom Is Stored in the Trees\u201d\u2014Degrading BCR-ABL with Berberis Vulgaris","volume":"26","author":"Elf","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_50","first-page":"384","article-title":"Effect of Berberine on the Differentiation and Apoptosis of K562 Cell Line","volume":"32","author":"Jin","year":"2009","journal-title":"J. Chin. Med. Mater."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1158\/1078-0432.CCR-19-2460","article-title":"Discovery of Berberine That Targetedly Induces Autophagic Degradation of Both BCR-ABL and BCR-ABL T315I through Recruiting LRSAM1 for Overcoming Imatinib Resistance","volume":"26","author":"Yin","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.2174\/1871520622666220324092302","article-title":"Effects of Berberine on Leukemia with a Focus on Its Molecular Targets","volume":"22","author":"Mazandaranian","year":"2022","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1039\/D2FO03331C","article-title":"Berberine Hydrochloride Alleviates Imatinib Mesylate\u2014Induced Cardiotoxicity through the Inhibition of Nrf2-Dependent Ferroptosis","volume":"14","author":"Song","year":"2023","journal-title":"Food Funct."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8485","DOI":"10.1007\/s00210-024-03199-0","article-title":"Research Progress on Pharmacological Effects and Bioavailability of Berberine","volume":"397","author":"Cui","year":"2024","journal-title":"Naunyn.-Schmiedeberg\u2019s. Arch. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Solnier, J., Zhang, Y., Kuo, Y., Du, M., Roh, K., Gahler, R., Wood, S., and Chang, C. (2023). Characterization and Pharmacokinetic Assessment of a New Berberine Formulation with Enhanced Absorption In Vitro and in Human Volunteers. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15112567"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"157030","DOI":"10.1016\/j.phymed.2025.157030","article-title":"Multiple Target and Regulatory Pathways of Berberine","volume":"146","author":"Zhou","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1182\/blood-2003-11-4065","article-title":"Chlorogenic Acid Inhibits Bcr-Abl Tyrosine Kinase and Triggers P38 Mitogen-Activated Protein Kinase\u2013Dependent Apoptosis in Chronic Myelogenous Leukemic Cells","volume":"104","author":"Bandyopadhyay","year":"2004","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.bcp.2010.08.013","article-title":"Involvement of ROS in Chlorogenic Acid-Induced Apoptosis of Bcr-Abl+ CML Cells","volume":"80","author":"Rakshit","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"979414","DOI":"10.1155\/2014\/979414","article-title":"Pharmacokinetics and Tissue Distribution Study of Chlorogenic Acid from Lonicerae Japonicae Flos Following Oral Administrations in Rats","volume":"2014","author":"Zhou","year":"2014","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/jn\/133.6.1853","article-title":"Chlorogenic Acid Bioavailability Largely Depends on Its Metabolism by the Gut Microflora in Rats","volume":"133","author":"Gonthier","year":"2003","journal-title":"J. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.abb.2010.03.005","article-title":"Bioavailability of Chlorogenic Acids Following Acute Ingestion of Coffee by Humans with an Ileostomy","volume":"501","author":"Stalmach","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Nguyen, V., Taine, E.G., Meng, D., Cui, T., and Tan, W. (2024). Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials. Nutrients, 16.","DOI":"10.3390\/nu16070924"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e70017","DOI":"10.1111\/bcpt.70017","article-title":"Effect of Acute Exposure of Swiss Mice to Chlorogenic Acid","volume":"136","author":"Afolabi","year":"2025","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/leu.2008.74","article-title":"Effective Killing of Gleevec-Resistant CML Cells with T315I Mutation by a Natural Compound PEITC through Redox-Mediated Mechanism","volume":"22","author":"Zhang","year":"2008","journal-title":"Leukemia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"543","DOI":"10.3892\/mmr.2014.2167","article-title":"Phenethyl Isothiocyanate Inhibits Growth of Human Chronic Myeloid Leukemia K562 Cells via Reactive Oxygen Species Generation and Caspases","volume":"10","author":"Wang","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.1158\/0008-5472.CAN-15-1544","article-title":"Naturally Occurring Isothiocyanates Exert Anticancer Effects by Inhibiting Deubiquitinating Enzymes","volume":"75","author":"Lawson","year":"2015","journal-title":"Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cbi.2015.10.004","article-title":"Inhibition of Crosstalk between Bcr-Abl and PKC Signaling by PEITC, Augments Imatinib Sensitivity in Chronic Myelogenous Leukemia Cells","volume":"242","author":"Roy","year":"2015","journal-title":"Chem.-Biol. Interact."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1007\/s11095-005-7097-z","article-title":"Pharmacokinetics of Dietary Phenethyl Isothiocyanate in Rats","volume":"22","author":"Ji","year":"2005","journal-title":"Pharm. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Coscueta, E.R., Sousa, A.S., Reis, C.A., and Pintado, M.M. (2022). Phenylethyl Isothiocyanate: A Bioactive Agent for Gastrointestinal Health. Molecules, 27.","DOI":"10.3390\/molecules27030794"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lam-Ubol, A., Sukhaboon, J., Rasio, W., Tupwongse, P., Tangshewinsirikul, T., and Trachootham, D. (2023). Nutri-PEITC Jelly Significantly Improves Progression-Free Survival and Quality of Life in Patients with Advanced Oral and Oropharyngeal Cancer: A Blinded Randomized Placebo-Controlled Trial. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097824"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.tiv.2011.12.018","article-title":"Anti-Leukemic Effects of Gallic Acid on Human Leukemia K562 Cells: Downregulation of COX-2, Inhibition of BCR\/ABL Kinase and NF-\u039aB Inactivation","volume":"26","author":"Aparna","year":"2012","journal-title":"Toxicol. Vitr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1002\/mnfr.201200167","article-title":"Gallic Acid Downregulates Matrix Metalloproteinase-2 (MMP-2) and MMP-9 in Human Leukemia Cells with Expressed Bcr\/Abl","volume":"56","author":"Chen","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.compbiolchem.2018.04.001","article-title":"Computational Study of Molecular Electrostatic Potential, Docking and Dynamics Simulations of Gallic Acid Derivatives as ABL Inhibitors","volume":"74","author":"Raghi","year":"2018","journal-title":"Comput. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Xiang, W., Sng, C., Lam, Y.-H., Kok, Z.-H., Linn, Y.-C., Neo, S.-Y., Siew, Y.-Y., Singh, D., Koh, H.-L., and Chuah, C. (2024). Gallic Acid Enhances the Efficacy of BCR::ABL1 Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia through Inhibition of Mitochondrial Respiration and Modulation of Oncogenic Signaling Pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147958"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jchromb.2013.11.007","article-title":"Simultaneous Detection of Green Tea Catechins and Gallic Acid in Human Serum after Ingestion of Green Tea Tablets Using Ion-Pair High-Performance Liquid Chromatography with Electrochemical Detection","volume":"945\u2013946","author":"Narumi","year":"2014","journal-title":"J. Chromatogr. B"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"114068","DOI":"10.1016\/j.foodres.2024.114068","article-title":"Dietary Gallic Acid as an Antioxidant: A Review of Its Food Industry Applications, Health Benefits, Bioavailability, Nano-Delivery Systems, and Drug Interactions","volume":"180","author":"Xiang","year":"2024","journal-title":"Food Res. Int."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Chen, P., Zou, F., and Liu, W. (2025). Recent Advancement in Prevention against Hepatotoxicity, Molecular Mechanisms, and Bioavailability of Gallic Acid, a Natural Phenolic Compound: Challenges and Perspectives. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1549526"},{"key":"ref_78","first-page":"225","article-title":"Pharmacological Effects of Gallic Acid in Health and Diseases: A Mechanistic Review","volume":"22","author":"Kahkeshani","year":"2019","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Truzzi, F., Valerii, M.C., Tibaldi, C., Zhang, Y., Abduazizova, V., Spisni, E., and Dinelli, G. (2020). Are Supplements Safe? Effects of Gallic and Ferulic Acids on In Vitro Cell Models. Nutrients, 12.","DOI":"10.3390\/nu12061591"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chi, H., and Ly, B. (2022). Artemisia Vulgaris Inhibits BCR\/ABL and Promotes Apoptosis in Chronic Myeloid Leukemia Cells. Biomed. Rep., 17.","DOI":"10.3892\/br.2022.1575"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.vph.2007.05.002","article-title":"Artesunate Inhibits Angiogenesis and Downregulates Vascular Endothelial Growth Factor Expression in Chronic Myeloid Leukemia K562 Cells","volume":"47","author":"Zhou","year":"2007","journal-title":"Vasc. Pharmacol."},{"key":"ref_82","first-page":"5416","article-title":"Effects of Imatinib and Artemisia Vulgaris Extracts in Combination on Leukemia Cell Proliferation","volume":"16","year":"2023","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s12936-024-05085-9","article-title":"Safety and Pharmacokinetic Properties of a New Formulation of Parenteral Artesunate in Healthy Thai Volunteers","volume":"23","author":"Tarning","year":"2024","journal-title":"Malar. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1093\/cid\/ciab570","article-title":"Safety and Effectiveness of Intravenous Artesunate for Treatment of Severe Malaria in the United States\u2014April 2019 Through December 2020","volume":"73","author":"Abanyie","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_85","unstructured":"National Institute of Diabetes and Digestive and Kidney Diseases (2012). Artesunate."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1080\/03639045.2022.2050751","article-title":"Aloe Vera and Artemisia Vulgaris Hydrogels: Exploring the Toxic Effects of Structural Transformation of the Biocompatible Materials","volume":"47","author":"Frasat","year":"2021","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"58","DOI":"10.5187\/jast.2021.e8","article-title":"Artemisia Vulgaris Extract Causes Precocious Acrosome Reaction and Viability Loss but Low Rate of Membrane Damage in Mouse Spermatozoa","volume":"63","author":"Bhandari","year":"2021","journal-title":"J. Anim. Sci. Technol."},{"key":"ref_88","unstructured":"Famurewa Oluwatoyin, O.A.U. (2025, September 15). Improving Treatment Outcomes in Chronic Myeloid Leukaemia Patients Using Imatinib and Artesunate Combination Therapy, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07022743?intr=Artesunate&rank=9&utm_source=chatgpt.com."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Malik, V., Radhakrishnan, N., Kaul, S.C., Wadhwa, R., and Sundar, D. (2022). Computational Identification of BCR-ABL Oncogenic Signaling as a Candidate Target of Withaferin A and Withanone. Biomolecules, 12.","DOI":"10.3390\/biom12020212"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.2147\/DDDT.S422512","article-title":"Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment\u2014Pharmacology and Mechanisms","volume":"17","author":"Xing","year":"2023","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.toxrep.2022.05.012","article-title":"Safety, Toxicity and Pharmacokinetic Assessment of Oral Withaferin-A in Mice","volume":"9","author":"Gupta","year":"2022","journal-title":"Toxicol. Rep."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1158\/1078-0432.CCR-08-2141","article-title":"Triptolide Inhibits Bcr-Abl Transcription and Induces Apoptosis in STI571-Resistant Chronic Myelogenous Leukemia Cells Harboring T315I Mutation","volume":"15","author":"Shi","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_93","first-page":"1148","article-title":"Triptolide Inhibits Proliferation and Induces Apoptosis of Imatinib Resistant K562\/G01 Cells","volume":"21","author":"Wen","year":"2013","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1016\/j.bmc.2010.01.052","article-title":"Design, Synthesis, and Biological Evaluation of Novel Water-Soluble Triptolide Derivatives: Antineoplastic Activity against Imatinib-Resistant CML Cells Bearing T315I Mutant Bcr-Abl","volume":"18","author":"Xu","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2231765","DOI":"10.1080\/16078454.2023.2231765","article-title":"The Roles of TPL in Hematological Malignancies","volume":"28","author":"Xu","year":"2023","journal-title":"Hematology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1158\/1535-7163.MCT-09-0386","article-title":"Triptolide Induces Cell Death Independent of Cellular Responses to Imatinib in Blast Crisis Chronic Myelogenous Leukemia Cells Including Quiescent CD34+ Primitive Progenitor Cells","volume":"8","author":"Mak","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1007\/s13346-020-00827-z","article-title":"Therapeutic Applications and Delivery Systems for Triptolide","volume":"10","author":"Viegas","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Cui, D., Xu, D., Yue, S., Yan, C., Liu, W., Fu, R., Ma, W., and Tang, Y. (2023). Recent Advances in the Pharmacological Applications and Liver Toxicity of Triptolide. Chem.-Biol. Interact., 382.","DOI":"10.1016\/j.cbi.2023.110651"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Song, J., He, G.-N., and Dai, L. (2023). A Comprehensive Review on Celastrol, Triptolide and Triptonide: Insights on Their Pharmacological Activity, Toxicity, Combination Therapy, New Dosage Form and Novel Drug Delivery Routes. Biomed. Pharmacother., 162.","DOI":"10.1016\/j.biopha.2023.114705"},{"key":"ref_100","first-page":"10181","article-title":"Pharmacological Activity and Clinical Progress of Triptolide and Its Derivatives LLDT-8, PG490-88Na, and Minnelide: A Narrative Review","volume":"27","author":"Zeng","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1158\/1078-0432.CCR-13-1063","article-title":"Gambogic Acid Induces Apoptosis in Imatinib-Resistant Chronic Myeloid Leukemia Cells via Inducing Proteasome Inhibition and Caspase-Dependent Bcr-Abl Downregulation","volume":"20","author":"Shi","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.3109\/10428194.2015.1018251","article-title":"Gambogic Acid Induces Death of K562 Cells through Autophagy and Apoptosis Mechanisms","volume":"56","author":"Chen","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.ejps.2018.10.001","article-title":"Development of a Safety and Efficacy Nanoemulsion Delivery System Encapsulated Gambogic Acid for Acute Myeloid Leukemia in Vitro and in Vivo","volume":"125","author":"Feng","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1021\/acsabm.9b00419","article-title":"Next-Generation Noncompetitive Nanosystems Based on Gambogic Acid: In Silico Identification of Transferrin Receptor Binding Sites, Regulatory Shelf Stability, and Their Preliminary Safety in Healthy Rodents","volume":"2","author":"Arora","year":"2019","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Hatami, E., Jaggi, M., Chauhan, S.C., and Yallapu, M.M. (2020). Gambogic Acid: A Shining Natural Compound to Nanomedicine for Cancer Therapeutics. Biochim. Biophys. Acta (BBA)-Rev. Cancer, 1874.","DOI":"10.1016\/j.bbcan.2020.188381"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.canlet.2009.09.006","article-title":"Celastrol, a Novel HSP90 Inhibitor, Depletes Bcr\u2013Abl and Induces Apoptosis in Imatinib-Resistant Chronic Myelogenous Leukemia Cells Harboring T315I Mutation","volume":"290","author":"Lu","year":"2010","journal-title":"Cancer Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"155937","DOI":"10.1016\/j.phymed.2024.155937","article-title":"Celastrol Induces DNA Damage and Cell Death in BCR-ABL T315I-Mutant CML by Targeting YY1 and HMCES","volume":"134","author":"Yang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_108","first-page":"465","article-title":"Celastrol and an EGCG Pro-Drug Exhibit Potent Chemosensitizing Activity in Human Leukemia Cells","volume":"25","author":"Davenport","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.2147\/DDDT.S389977","article-title":"Celastrol: A Potential Natural Lead Molecule for New Drug Design, Development and Therapy for Memory Impairment","volume":"17","author":"Sekar","year":"2023","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhang, J., Duan, X., Zhao, G., and Zhang, M. (2022). Celastrol: A Promising Agent Fighting against Cardiovascular Diseases. Antioxidants, 11.","DOI":"10.3390\/antiox11081597"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Shi, J., Li, J., Xu, Z., Chen, L., Luo, R., Zhang, C., Gao, F., Zhang, J., and Fu, C. (2020). Celastrol: A Review of Useful Strategies Overcoming Its Limitation in Anticancer Application. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.558741"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Sun, Y., Wang, C., Li, X., Lu, J., and Wang, M. (2024). Recent Advances in Drug Delivery of Celastrol for Enhancing Efficiency and Reducing the Toxicity. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1137289"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Zhan, S., Paik, A., Onyeabor, F., Ding, B., Prabhu, S., and Wang, J. (2020). Oral Bioavailability Evaluation of Celastrol-Encapsulated Silk Fibroin Nanoparticles Using an Optimized LC-MS\/MS Method. Molecules, 25.","DOI":"10.3390\/molecules25153422"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bcp.2019.02.028","article-title":"Andrographolide and Its Potent Derivative Exhibit Anticancer Effects against Imatinib-Resistant Chronic Myeloid Leukemia Cells by Downregulating the Bcr-Abl Oncoprotein","volume":"163","author":"Liao","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.bcp.2013.10.014","article-title":"Andrographolide Downregulates the V-Src and Bcr-Abl Oncoproteins and Induces Hsp90 Cleavage in the ROS-Dependent Suppression of Cancer Malignancy","volume":"87","author":"Liu","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Hsu, Y.-H., Hsu, Y.-L., Liu, S.-H., Liao, H.-C., Lee, P.-X., Lin, C.-H., Lo, L.-C., and Fu, S.-L. (2016). Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152770"},{"key":"ref_117","first-page":"1","article-title":"Andrographolide: Its Pharmacology, Natural Bioavailability and Current Approaches to Increase Its Content in Andrographispaniculata","volume":"11","author":"Pandey","year":"2018","journal-title":"Int. J. Complement. Altern. Med."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Songvut, P., Suriyo, T., Panomvana, D., Rangkadilok, N., and Satayavivad, J. (2022). A Comprehensive Review on Disposition Kinetics and Dosage of Oral Administration of Andrographis Paniculata, an Alternative Herbal Medicine, in Co-Treatment of Coronavirus Disease. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.952660"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1080\/13880209.2024.2444446","article-title":"Non-Linear Oral Bioavailability and Clinical Pharmacokinetics of High-Dose Andrographis Paniculata Ethanolic Extract: Relevant Dosage Implications for COVID-19 Treatment","volume":"63","author":"Songvut","year":"2025","journal-title":"Pharm. Biol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/13880209.2024.2311201","article-title":"Enhancing Oral Bioavailability of Andrographolide Using Solubilizing Agents and Bioenhancer: Comparative Pharmacokinetics of Andrographis Paniculata Formulations in Beagle Dogs","volume":"62","author":"Songvut","year":"2024","journal-title":"Pharm. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Songvut, P., Rangkadilok, N., Pholphana, N., Suriyo, T., Panomvana, D., Puranajoti, P., Akanimanee, J., and Satayavivad, J. (2023). Comparative Pharmacokinetics and Safety Evaluation of High Dosage Regimens of Andrographis Paniculata Aqueous Extract after Single and Multiple Oral Administration in Healthy Participants. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1230401"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/ptr.7324","article-title":"Andrographolide: A Review of Its Pharmacology, Pharmacokinetics, Toxicity and Clinical Trials and Pharmaceutical Researches","volume":"36","author":"Zeng","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1111\/bph.13146","article-title":"A Derivative of Epigallocatechin-3-gallate Induces Apoptosis via SHP-1-mediated Suppression of BCR-ABL and STAT3 Signalling in Chronic Myelogenous Leukaemia","volume":"172","author":"Jung","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.3892\/or.2015.4086","article-title":"Green Tea Polyphenol Epigallocatechin-O-Gallate Induces Cell Death by Acid Sphingomyelinase Activation in Chronic Myeloid Leukemia Cells","volume":"34","author":"Huang","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1089\/omi.2024.0074","article-title":"S1P Signaling Genes as Prominent Drivers of BCR-ABL1-Independent Imatinib Resistance and Six Herbal Compounds as Potential Drugs for Chronic Myeloid Leukemia","volume":"28","author":"Morang","year":"2024","journal-title":"OMICS A J. Integr. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ejphar.2018.09.005","article-title":"Epigallocatechin-3-Gallate and BIX-01294 Have Different Impact on Epigenetics and Senescence Modulation in Acute and Chronic Myeloid Leukemia Cells","volume":"838","author":"Vitkeviciene","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_127","first-page":"992","article-title":"Synergistic Effect of Ponatinib and Epigallocatechin-3-Gallate Induces Apoptosis in Chronic Myeloid Leukemia Cells through Altering Expressions of Cell Cycle Regulatory Genes","volume":"19","author":"Goker","year":"2014","journal-title":"J. BUON"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/1440-1681.13037","article-title":"(\u2212)-Epigallocatechin-3-gallate Induces Cell Apoptosis in Chronic Myeloid Leukaemia by Regulating Bcr\/Abl-mediated P38-MAPK\/JNK and JAK 2\/STAT 3\/AKT Signalling Pathways","volume":"46","author":"Xiao","year":"2019","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Andreu Fern\u00e1ndez, V., Almeida Toledano, L., Pizarro Lozano, N., Navarro Tapia, E., G\u00f3mez Roig, M.D., De la Torre Fornell, R., and Garc\u00eda Algar, \u00d3. (2020). Bioavailability of Epigallocatechin Gallate Administered with Different Nutritional Strategies in Healthy Volunteers. Antioxidants, 9.","DOI":"10.3390\/antiox9050440"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Ferrari, E., and Naponelli, V. (2025). Catechins and Human Health: Breakthroughs from Clinical Trials. Molecules, 30.","DOI":"10.3390\/molecules30153128"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Dusemund, B., Filipi\u010d, M., Frutos, M.J., Galtier, P., and Gott, D. (2018). Scientific Opinion on the Safety of Green Tea Catechins. EFSA J., 16, e05239.","DOI":"10.2903\/j.efsa.2018.5239"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/ejcn.2016.78","article-title":"Liver-Related Safety Assessment of Green Tea Extracts in Humans: A Systematic Review of Randomized Controlled Trials","volume":"70","author":"Isomura","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"70794","DOI":"10.18632\/oncotarget.12222","article-title":"Randomized, Placebo-Controlled Trial Evaluating the Safety of One-Year Administration of Green Tea Catechins","volume":"7","author":"Kumar","year":"2016","journal-title":"Oncotarget"},{"key":"ref_134","first-page":"572","article-title":"Effect of Curcumin on STAT5 Signaling Pathway in Primary CML Cells","volume":"12","author":"Chen","year":"2004","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1179\/102453308X343437","article-title":"Curcumin Inhibits Proliferation and Induces Apoptosis of Leukemic Cells Expressing Wild-Type or T315I-BCR-ABL and Prolongs Survival of Mice with Acute Lymphoblastic Leukemia","volume":"13","author":"William","year":"2008","journal-title":"Hematology"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Feriotto, G., Marchetti, P., Rondanin, R., Tagliati, F., Aguzzi, S., Beninati, S., Casciano, F., Tabolacci, C., and Mischiati, C. (2023). Cytotoxicity of Isoxazole Curcumin Analogs on Chronic Myeloid Leukemia-Derived K562 Cell Lines Sensitive and Resistant to Imatinib. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032356"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/01635581.2018.1380208","article-title":"Synergistic Induction of Apoptosis by Quercetin and Curcumin in Chronic Myeloid Leukemia (K562) Cells","volume":"70","author":"Taga","year":"2018","journal-title":"Nutr. Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.1182\/blood.V110.11.4537.4537","article-title":"Combined Treatment of STI571 (Glivec) and Curcumin Synergistically Suppresses the Growth of K562 Cells Via Inhibition of Bcr-Abl Pathway","volume":"110","author":"Park","year":"2007","journal-title":"Blood"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biocel.2015.05.003","article-title":"Curcumin Potentiates the Anti-Leukemia Effects of Imatinib by Downregulation of the AKT\/MTOR Pathway and BCR\/ABL Gene Expression in Ph+ Acute Lymphoblastic Leukemia","volume":"65","author":"Guo","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4143\/crt.2014.46.1.2","article-title":"Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: The Golden Pigment from Golden Spice","volume":"46","author":"Prasad","year":"2014","journal-title":"Cancer Res. Treat."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3477","DOI":"10.1007\/s00210-023-02825-7","article-title":"Clinical Trials on Curcumin in Relation to Its Bioavailability and Effect on Malignant Diseases: Critical Analysis","volume":"397","author":"Khosravi","year":"2024","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1021\/acsomega.2c07326","article-title":"Curcumin Formulations for Better Bioavailability: What We Learned from Clinical Trials Thus Far?","volume":"8","author":"Hegde","year":"2023","journal-title":"ACS Omega"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1007\/s12325-022-02081-w","article-title":"Superior Bioavailability of a Novel Curcumin Formulation in Healthy Humans Under Fasting Conditions","volume":"39","author":"Kothaplly","year":"2022","journal-title":"Adv. Ther."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1208\/s12248-012-9432-8","article-title":"Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials","volume":"15","author":"Gupta","year":"2013","journal-title":"AAPS J."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Hewlings, S., and Kalman, D. (2017). Curcumin: A Review of Its Effects on Human Health. Foods, 6.","DOI":"10.3390\/foods6100092"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1177\/1078155211416530","article-title":"Effect of Imatinib Therapy with and without Turmeric Powder on Nitric Oxide Levels in Chronic Myeloid Leukemia","volume":"18","author":"Ghalaut","year":"2012","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1096\/fj.07-101394","article-title":"Imatinib Mesylate-resistant Human Chronic Myelogenous Leukemia Cell Lines Exhibit High Sensitivity to the Phytoalexin Resveratrol","volume":"22","author":"Puissant","year":"2008","journal-title":"FASEB J."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1097\/CAD.0000000000000635","article-title":"Resveratrol Inhibits STAT5 Activation through the Induction of SHP-1 and SHP-2 Tyrosine Phosphatases in Chronic Myelogenous Leukemia Cells","volume":"29","author":"Li","year":"2018","journal-title":"Anticancer Drugs"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/aps.2014.132","article-title":"Resveratrol Induces Apoptosis of Human Chronic Myelogenous Leukemia Cells in Vitro through P38 and JNK-Regulated H2AX Phosphorylation","volume":"36","author":"Wu","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Banerjee Mustafi, S., Chakraborty, P.K., and Raha, S. (2010). Modulation of Akt and ERK1\/2 Pathways by Resveratrol in Chronic Myelogenous Leukemia (CML) Cells Results in the Downregulation of Hsp70. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008719"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"118599","DOI":"10.1016\/j.ijpharm.2019.118599","article-title":"Targeted Cancer Treatment Using a Combination of SiRNA-Liposomes and Resveratrol-Electrospun Fibers in Co-Cultures","volume":"569","author":"Madihally","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.4238\/2015.June.11.17","article-title":"Inhibition of Human Chronic Myelogenous Leukemia K562 Cell Growth Following Combination Treatment with Resveratrol and Imatinib Mesylate","volume":"14","author":"Wang","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"164","DOI":"10.3892\/etm.2015.2895","article-title":"Bioavailability and Safety Study of Resveratrol 500 Mg Tablets in Healthy Male and Female Volunteers","volume":"11","author":"Sergides","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"140475","DOI":"10.1016\/j.foodchem.2024.140475","article-title":"Recent Advances in Encapsulation of Resveratrol for Enhanced Delivery","volume":"460","author":"Dikmetas","year":"2024","journal-title":"Food Chem."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Salla, M., Karaki, N., El Kaderi, B., Ayoub, A.J., Younes, S., Abou Chahla, M.N., Baksh, S., and El Khatib, S. (2024). Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16040569"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Cavalcante de Freitas, P.G., Rodrigues Arruda, B., Ara\u00fajo Mendes, M.G., Barroso de Freitas, J.V., da Silva, M.E., Sampaio, T.L., Petrilli, R., and Eloy, J.O. (2023). Resveratrol-Loaded Polymeric Nanoparticles: The Effects of D-\u03b1-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) on Physicochemical and Biological Properties against Breast Cancer In Vitro and In Vivo. Cancers, 15.","DOI":"10.3390\/cancers15102802"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Montalesi, E., Cracco, P., Acconcia, F., Fiocchetti, M., Iucci, G., Battocchio, C., Orlandini, E., Ciccone, L., Nencetti, S., and Muzzi, M. (2023). Resveratrol Analogs and Prodrugs Differently Affect the Survival of Breast Cancer Cells Impairing Estrogen\/Estrogen Receptor \u03b1\/Neuroglobin Pathway. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032148"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Radeva, L., and Yoncheva, K. (2025). Resveratrol\u2014A Promising Therapeutic Agent with Problematic Properties. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17010134"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Ruparelia, K.C., Zeka, K., Beresford, K.J.M., Wilsher, N.E., Potter, G.A., Androutsopoulos, V.P., Brucoli, F., and Arroo, R.R.J. (2024). CYP1-Activation and Anticancer Properties of Synthetic Methoxylated Resveratrol Analogues. Molecules, 29.","DOI":"10.3390\/molecules29020423"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Shaito, A., Posadino, A.M., Younes, N., Hasan, H., Halabi, S., Alhababi, D., Al-Mohannadi, A., Abdel-Rahman, W.M., Eid, A.H., and Nasrallah, G.K. (2020). Potential Adverse Effects of Resveratrol: A Literature Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062084"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Wang, J., Liu, T., Chen, P., Yin, D., Zhang, H., Qiu, X., Zou, S., and Li, W. (2025). Pharmacokinetic Evaluation of Two Oral Resveratrol Formulations in a Randomized, Open-Label, Crossover Study in Healthy Fasting Subjects. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-08665-0"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Sarno, F., Pepe, G., Termolino, P., Carafa, V., Massaro, C., Merciai, F., Campiglia, P., Nebbioso, A., and Altucci, L. (2020). Trifolium Repens Blocks Proliferation in Chronic Myelogenous Leukemia via the BCR-ABL\/STAT5 Pathway. Cells, 9.","DOI":"10.3390\/cells9020379"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"4468","DOI":"10.1080\/14786419.2023.2299319","article-title":"Investigation of Trifolium Repens L. from the Indian Himalayan Region as a Phyto-Therapeutic Agent","volume":"38","author":"Ngangom","year":"2024","journal-title":"Nat. Prod. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3390\/foods4030338","article-title":"Trifolium Pratense and T. Repens (Leguminosae): Edible Flower Extracts as Functional Ingredients","volume":"4","author":"Tundis","year":"2015","journal-title":"Foods"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"20200015","DOI":"10.1515\/jbcpp-2020-0015","article-title":"Phytochemical Profile and Pharmacological Properties of Trifolium Repens","volume":"32","author":"Ahmad","year":"2021","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Tjeerdsma, A.M., van Hunsel, F.P.A.M., van de Koppel, S., Ekhart, C., Vitalone, A., and Woerdenbag, H.J. (2023). Analysis of Safety Concerns on Herbal Products with Assumed Phytoestrogenic Activity. Pharmaceuticals, 16.","DOI":"10.3390\/ph16081137"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Lu, X., Geng, J., Zhang, J., Miao, J., and Liu, M. (2019). Xanthohumol, a Prenylated Flavonoid from Hops, Induces Caspase-Dependent Degradation of Oncoprotein BCR-ABL in K562 Cells. Antioxidants, 8.","DOI":"10.3390\/antiox8090402"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1158\/1535-7163.MCT-08-0132","article-title":"Antileukemia Effects of Xanthohumol in Bcr\/Abl-Transformed Cells Involve Nuclear Factor-\u039aB and P53 Modulation","volume":"7","author":"Monteghirfo","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/mnfr.201300333","article-title":"Human Pharmacokinetics of Xanthohumol, an Antihyperglycemic Flavonoid from Hops","volume":"58","author":"Legette","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Zugravu, C.-A., Bohiltea, R.-E., Salmen, T., Pogurschi, E., and Otelea, M.R. (2022). Antioxidants in Hops: Bioavailability, Health Effects and Perspectives for New Products. Antioxidants, 11.","DOI":"10.3390\/antiox11020241"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2100831","DOI":"10.1002\/mnfr.202100831","article-title":"Bioavailability and Cardiometabolic Effects of Xanthohumol: Evidence from Animal and Human Studies","volume":"66","author":"Neumann","year":"2022","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"21918","DOI":"10.18632\/oncotarget.4204","article-title":"Curcumin Inhibits in Vitro and in Vivo Chronic Myelogenous Leukemia Cells Growth: A Possible Role for Exosomal Disposal of MiR-21","volume":"6","author":"Taverna","year":"2015","journal-title":"Oncotarget"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"100484","DOI":"10.4251\/wjgo.v17.i4.100484","article-title":"Natural Products and Cancer: The Urgent Need to Bridge the Gap between Preclinical and Clinical Research","volume":"17","author":"Rojas","year":"2025","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"e34462","DOI":"10.1016\/j.heliyon.2024.e34462","article-title":"Plant Natural Compounds in the Cancer Treatment: A Systematic Bibliometric Analysis","volume":"10","author":"Wang","year":"2024","journal-title":"Heliyon"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Cotoraci, C., Ciceu, A., Sasu, A., Miutescu, E., and Hermenean, A. (2021). The Anti-Leukemic Activity of Natural Compounds. Molecules, 26.","DOI":"10.3390\/molecules26092709"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"100215","DOI":"10.1016\/j.wds.2025.100215","article-title":"Sustainable Healing: Natural Compounds Facilitating the Future Cancer Treatment","volume":"6","author":"Mir","year":"2025","journal-title":"World Dev. Sustain."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s43094-023-00465-5","article-title":"Anticancer Plant-Derivatives: Deciphering Their Oncopreventive and Therapeutic Potential in Molecular Terms","volume":"9","author":"Gahtori","year":"2023","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Moriello, C., De Rosa, C., D\u2019Angelo, S., and Pasquale, P. (2025). Polyphenols and Chronic Myeloid Leukemia: Emerging Therapeutic Opportunities. Hemato, 6.","DOI":"10.3390\/hemato6030028"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/21\/4160\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T08:14:47Z","timestamp":1761207287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/21\/4160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,22]]},"references-count":178,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["molecules30214160"],"URL":"https:\/\/doi.org\/10.3390\/molecules30214160","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,22]]}}}