{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T11:41:24Z","timestamp":1793619684766,"version":"4.5.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-11643-1","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:21:09Z","timestamp":1759242069000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vitamin B17 alleviates Sorafenib-induced cardiotoxicity in Ehrlich Ascites Carcinoma mice via modulation of inflammatory and fibrotic pathways"],"prefix":"10.1038","volume":"15","author":[{"given":"Afrah Fatthi","family":"Salama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Elmetwalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyaa","family":"Elmalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Abu","family":"El-Magd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hewida Hassan","family":"Fadel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"11643_CR1","doi-asserted-by":"crossref","unstructured":"Sapna, F. N. U. et al. Advancements in heart failure management: a comprehensive narrative review of emerging therapies, Cureus, vol. 15, no. 10, (2023).","DOI":"10.7759\/cureus.46486"},{"issue":"11","key":"11643_CR2","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.cardfail.2014.08.004","volume":"20","author":"FY Anthony","year":"2014","unstructured":"Anthony, F. Y., Steingart, R. M. & Fuster, V. Cardiomyopathy associated with cancer therapy. J. Card Fail. 20 (11), 841\u2013852 (2014).","journal-title":"J. Card Fail."},{"key":"11643_CR3","doi-asserted-by":"crossref","unstructured":"Li, J. et al. Understanding Sorafenib-Induced cardiovascular toxicity: mechanisms and treatment implications. Drug Des. Devel Ther. 18 (12), 829\u2013843 (2024).","DOI":"10.2147\/DDDT.S443107"},{"issue":"1","key":"11643_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-022-10517-0","volume":"12","author":"AA Attia","year":"2022","unstructured":"Attia, A. A. et al. Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich Ascites carcinoma and ameliorates the associated liver damage. Sci. Rep. 12 (1), 1\u20139 (2022).","journal-title":"Sci. Rep."},{"issue":"1","key":"11643_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12906-023-04142-1","volume":"23","author":"T El-Sewedy","year":"2023","unstructured":"El-Sewedy, T. et al. Hepatocellular carcinoma cells: activity of amygdalin and Sorafenib in targeting ampk\/mtor and BCL-2 for anti-angiogenesis and apoptosis cell death. BMC Complement. Med. Ther. 23 (1), 1\u201317 (2023).","journal-title":"BMC Complement. Med. Ther."},{"issue":"5","key":"11643_CR6","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1080\/03601234.2017.1421841","volume":"53","author":"J Kop ekov","year":"2018","unstructured":"Kop ekov, J. et al. Influence of long-term consumption of bitter apricot seeds on risk factors for cardiovascular diseases. J. Environ. Sci. Heal Part. B. 53 (5), 298\u2013303 (2018).","journal-title":"J. Environ. Sci. Heal Part. B"},{"issue":"6","key":"11643_CR7","doi-asserted-by":"publisher","first-page":"8171","DOI":"10.3892\/mmr.2017.7609","volume":"16","author":"J Lv","year":"2017","unstructured":"Lv, J. et al. Amygdalin ameliorates the progression of atherosclerosis in LDL receptor\u2013deficient mice. mol. Med. Rep. 16 (6), 8171\u20138179 (2017).","journal-title":"mol. Med. Rep."},{"issue":"18","key":"11643_CR8","doi-asserted-by":"publisher","first-page":"14270","DOI":"10.3390\/ijms241814270","volume":"24","author":"M Spanoudaki","year":"2023","unstructured":"Spanoudaki, M. et al. Amygdalin as a promising Anti-cancer agent: molecular mechanisms and future perspectives for the development of new nanoformulations for its delivery. Int. J. Mol. Sci. 24 (18), 14270 (2023).","journal-title":"Int. J. Mol. Sci."},{"issue":"15","key":"11643_CR9","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.4161\/cc.21193","volume":"11","author":"M Cervello","year":"2012","unstructured":"Cervello, M. et al. Molecular mechanisms of Sorafenib action in liver cancer cells. Cell. Cycle. 11 (15), 2843\u20132855 (2012).","journal-title":"Cell. Cycle"},{"issue":"6","key":"11643_CR10","doi-asserted-by":"publisher","first-page":"535","DOI":"10.3109\/02841867909129082","volume":"18","author":"J Egawa","year":"1979","unstructured":"Egawa, J., Ishioka, K. & Ogata, T. Effect of irradiation and chemotherapeutic agents on the capillaries of Ehrlich Ascites carcinoma of mice. Acta Radiol. Oncol. Radiat. Phys. Biol. 18 (6), 535\u2013543 (1979).","journal-title":"Acta Radiol. Oncol. Radiat. Phys. Biol."},{"key":"11643_CR11","doi-asserted-by":"crossref","unstructured":"Vudatha, V. et al. Review of mechanisms and treatment of cancer-induced cardiac cachexia, Cells, vol. 11, no. 6, p. 1040, (2022).","DOI":"10.3390\/cells11061040"},{"issue":"1","key":"11643_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-23669-9","volume":"8","author":"S Mishra","year":"2018","unstructured":"Mishra, S. et al. Subcutaneous Ehrlich Ascites carcinoma mice model for studying cancer-induced cardiomyopathy. Sci. Rep. 8 (1), 1\u201311 (2018).","journal-title":"Sci. Rep."},{"issue":"2","key":"11643_CR13","first-page":"81","volume":"43","author":"A Ameen","year":"2023","unstructured":"Ameen, A. et al. Doxorubicin-Induced cardiotoxicity in adult male albino rats and the ameliorative effects of Achillea fragrantissima crude extract, its combined Ethyl acetate\/n. Butanol fraction, and vitamin E. Bull. Egypt. Soc. Physiol. Sci. 43 (2), 81\u2013107 (2023).","journal-title":"Bull. Egypt. Soc. Physiol. Sci."},{"key":"11643_CR14","doi-asserted-by":"crossref","unstructured":"Dubois-Deruy, E., Peugnet, V., Turkieh, A. & Pinet, F. Oxidative stress in cardiovascular diseases, Antioxidants, vol. 9, no. 9, p. 864, (2020).","DOI":"10.3390\/antiox9090864"},{"issue":"5","key":"11643_CR15","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1007\/s00018-020-03694-6","volume":"78","author":"H Men","year":"2021","unstructured":"Men, H. et al. The regulatory roles of p53 in cardiovascular health and disease. Cell. Mol. Life Sci. 78 (5), 2001\u20132018 (2021).","journal-title":"Cell. Mol. Life Sci."},{"key":"11643_CR16","doi-asserted-by":"crossref","unstructured":"Patil, P. P. et al. Effect of theobroma cacao L. On the efficacy and toxicity of doxorubicin in mice bearing ehrlich ascites carcinoma, Antioxidants, vol. 11, no. 6, p. 1094, (2022).","DOI":"10.3390\/antiox11061094"},{"issue":"1","key":"11643_CR17","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.pharmthera.2013.03.009","volume":"139","author":"GV Halade","year":"2013","unstructured":"Halade, G. V., Jin, Y. F. & Lindsey, M. L. Matrix metalloproteinase (MMP)-9: a proximal biomarker for cardiac remodeling and a distal biomarker for inflammation. Pharmacol. Ther. 139 (1), 32\u201340 (2013).","journal-title":"Pharmacol. Ther."},{"issue":"1","key":"11643_CR18","doi-asserted-by":"publisher","first-page":"40","DOI":"10.21608\/blj.2021.184392","volume":"17","author":"HM Nasser","year":"2021","unstructured":"Nasser, H. M., El-Naggar, S. A., El-Sayed Rizk, M. E. S. R., Elmetwalli, A. & Salama, A. F. Effect of Sorafenib on liver biochemistry prior to vitamin B17 coadministration in Ehrlich Ascites carcinoma mice model: preliminary phase study. Biochem. Lett. 17 (1), 40\u201349 (2021).","journal-title":"Biochem. Lett."},{"issue":"3","key":"11643_CR19","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1080\/01635581.2018.1508731","volume":"71","author":"MM Abboud","year":"2019","unstructured":"Abboud, M. M., Al Awaida, W., Alkhateeb, H. H. & Abu-Ayyad, A. N. Anti-tumor action of amygdalin on human breast cancer cells by selective sensitization to oxidative stress. Nutr. Cancer. 71 (3), 483\u2013490 (2019).","journal-title":"Nutr. Cancer"},{"issue":"05","key":"11643_CR20","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1142\/S0192415X22500586","volume":"50","author":"S Lin","year":"2022","unstructured":"Lin, S. et al. Amygdalin induced Mitochondria-Mediated apoptosis of lung Cancer cells via regulating NF \u03ba B-1\/NF \u03ba B signaling cascade in vitro and in vivo. Am. J. Chin. Med. 50 (05), 1361\u20131386 (2022).","journal-title":"Am. J. Chin. Med."},{"key":"11643_CR21","doi-asserted-by":"crossref","unstructured":"Elmetwalli, A. et al. Diarylheptanoids\/sorafenib as a potential anti-cancer combination against hepatocellular carcinoma: the p53\/MMP9 axis of action. Naunyn Schmiedebergs Arch. Pharmacol. 396 (10), 1\u201317 (2023).","DOI":"10.1007\/s00210-023-02470-0"},{"key":"11643_CR22","doi-asserted-by":"crossref","unstructured":"Besse, S., Nadaud, S., Balse, E. & Pavoine, C. Early protective role of inflammation in cardiac remodeling and heart failure: Focus on TNF\u03b1 and resident macrophages, Cells, vol. 11, no. 7, p. 1249, (2022).","DOI":"10.3390\/cells11071249"},{"issue":"11","key":"11643_CR23","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.2174\/1389450122666210203194036","volume":"22","author":"AR Kumar","year":"2021","unstructured":"Kumar, A. R., Devan, A. R., Nair, B. & Nath, L. R. Anti-VEGF mediated Immunomodulatory role of phytochemicals: scientific exposition for plausible HCC treatment. Curr. Drug Targets. 22 (11), 1288\u20131316 (2021).","journal-title":"Curr. Drug Targets"},{"issue":"2","key":"11643_CR24","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s12032-023-02284-3","volume":"41","author":"AF Salama","year":"2024","unstructured":"Salama, A. F. et al. Gingerol and\/or Sorafenib attenuates the DAB-induced HCC and hepatic portal vein dilatation via ATG4\/CASP3 and COIIV\/COX-2\/NF-\u03baB expression. Med. Oncol. 41 (2), 57 (2024).","journal-title":"Med. Oncol."},{"key":"11643_CR25","doi-asserted-by":"publisher","first-page":"615131","DOI":"10.3389\/fcell.2020.615131","volume":"8","author":"I Jridi","year":"2021","unstructured":"Jridi, I., Cant\u00e9-Barrett, K., Pike-Overzet, K. & Staal, F. J. T. Inflammation and Wnt signaling: target for Immunomodulatory therapy? Front. Cell. Dev. Biol. 8, 615131 (2021).","journal-title":"Front. Cell. Dev. Biol."},{"issue":"8","key":"11643_CR26","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.4314\/tjpr.v22i8.15","volume":"22","author":"WM Salama","year":"2023","unstructured":"Salama, W. M., El-Naggar, S. A. & ALRashdi, B. M. In vivo anti-tumor effect of Egyptian Scorpion Leiurus quinquestriatus venom in Ehrlich Ascites carcinomabearing mice. Trop. J. Pharm. Res. 22 (8), 1635\u20131643 (2023).","journal-title":"Trop. J. Pharm. Res."},{"issue":"1","key":"11643_CR27","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.jep.2010.03.010","volume":"129","author":"A Bala","year":"2010","unstructured":"Bala, A., Kar, B., Haldar, P. K., Mazumder, U. K. & Bera, S. Evaluation of anti-cancer activity of Cleome gynandra on ehrlich\u2019s Ascites carcinoma treated mice. J. Ethnopharmacol. 129 (1), 131\u2013134 (2010).","journal-title":"J. Ethnopharmacol."},{"issue":"1","key":"11643_CR28","doi-asserted-by":"publisher","first-page":"69","DOI":"10.21608\/blj.2021.198557","volume":"17","author":"A Elmalla","year":"2021","unstructured":"Elmalla, A., Elmetwalli, A., Rizk, M. E. S. & Salama, A. F. The effect of vitamin B17 on cardiomyopathy against Ehrlich tumor development in female mice. Biochem. Lett. 17 (1), 69\u201376 (2021).","journal-title":"Biochem. Lett."},{"issue":"1","key":"11643_CR29","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s12032-023-02236-x","volume":"41","author":"A Elmetwalli","year":"2023","unstructured":"Elmetwalli, A. et al. Novel phloretin-based combinations targeting glucose metabolism in hepatocellular carcinoma through GLUT2\/PEPCK axis of action: in Silico molecular modelling and in vivo studies. Med. Oncol. 41 (1), 12 (2023).","journal-title":"Med. Oncol."},{"key":"11643_CR30","doi-asserted-by":"crossref","unstructured":"Elmetwalli, A. et al. Modulation of the oxidative damage, inflammation, and apoptosis-related genes by dicinnamoyl-L-tartaric acid in liver cancer. Naunyn Schmiedebergs Arch. Pharmacol. 396 (11), 1\u201313 (2023).","DOI":"10.1007\/s00210-023-02511-8"},{"issue":"4","key":"11643_CR31","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.athoracsur.2020.01.025","volume":"110","author":"HN Al","year":"2020","unstructured":"Al, H. N. et al. Cor triatriatum sinister (divided left atrium): histopathologic features and clinical management. Ann. Thorac. Surg. 110 (4), 1380\u20131386 (2020).","journal-title":"Ann. Thorac. Surg."},{"key":"11643_CR32","doi-asserted-by":"crossref","unstructured":"Izzo, C. et al. The role of oxidative stress in cardiovascular aging and cardiovascular diseases, Life 11 (1),  60 (2021).","DOI":"10.3390\/life11010060"},{"issue":"4","key":"11643_CR33","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41569-021-00624-2","volume":"19","author":"M Mehdizadeh","year":"2022","unstructured":"Mehdizadeh, M., Aguilar, M., Thorin, E., Ferbeyre, G. & Nattel, S. The role of cellular senescence in cardiac disease: basic biology and clinical relevance. Nat. Rev. Cardiol. 19 (4), 250\u2013264 (2022).","journal-title":"Nat. Rev. Cardiol."},{"key":"11643_CR34","doi-asserted-by":"crossref","unstructured":"Congdon, J. M. Cardiovascular disease. Canine Feline Anesth. Co-Existing Dis. 1 (1), 1\u201385 (2022).","DOI":"10.1002\/9781119604075.ch1"},{"issue":"8","key":"11643_CR35","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1002\/ejhf.1858","volume":"22","author":"A Groenewegen","year":"2020","unstructured":"Groenewegen, A., Rutten, F. H., Mosterd, A. & Hoes, A. W. Epidemiology of heart failure. Eur. J. Heart Fail. 22 (8), 1342\u20131356 (2020).","journal-title":"Eur. J. Heart Fail."},{"key":"11643_CR36","doi-asserted-by":"publisher","first-page":"105253","DOI":"10.1016\/j.archger.2023.105253","volume":"117","author":"H Zhang","year":"2024","unstructured":"Zhang, H. et al. High serum lactate dehydrogenase as a predictor of cardiac insufficiency at follow-up in elderly patients with acute myocardial infarction. Arch. Gerontol. Geriatr. 117, 105253 (2024).","journal-title":"Arch. Gerontol. Geriatr."},{"key":"11643_CR37","doi-asserted-by":"crossref","unstructured":"Babuin, L. & Jaffe, A. S. Troponin: the biomarker of choice for the detection of cardiac injury, Cmaj, vol. 173, no. 10, pp. 1191\u20131202, (2005).","DOI":"10.1503\/cmaj\/051291"},{"issue":"9","key":"11643_CR38","doi-asserted-by":"publisher","first-page":"e0310253","DOI":"10.1371\/journal.pone.0310253","volume":"19","author":"Z Wang","year":"2024","unstructured":"Wang, Z., Du, H., Wan, H., Yang, J. & Wan, H. Amygdalin prevents multidrug-resistant Staphylococcus aureus-induced lung epithelial cell injury by regulating inflammation and oxidative stress. PLoS One. 19 (9), e0310253 (2024).","journal-title":"PLoS One"},{"key":"11643_CR39","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.ctim.2019.03.002","volume":"43","author":"J Mani","year":"2019","unstructured":"Mani, J. et al. Cyanide and lactate levels in patients during chronic oral amygdalin intake followed by intravenous amygdalin administration. Complement. Ther. Med. 43, 295\u2013299 (2019).","journal-title":"Complement. Ther. Med."},{"key":"11643_CR40","doi-asserted-by":"publisher","first-page":"110635","DOI":"10.1016\/j.colsurfb.2019.110635","volume":"185","author":"W Bei","year":"2020","unstructured":"Bei, W., Jing, L. & Chen, N. Cardio protective role of Wogonin loaded nanoparticle against isoproterenol induced myocardial infarction by moderating oxidative stress and inflammation. Colloids Surf. B Biointerfaces. 185, 110635 (2020).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"11643_CR41","doi-asserted-by":"crossref","unstructured":"Aldubayan, M. A. Evaluation of the cardiac protection conferred by proanthocyanidins in grape seeds against development of ehrlich solid tumors in mice, Biomed Res. Int., vol. 2020. (2020).","DOI":"10.1155\/2020\/3530296"},{"key":"11643_CR42","doi-asserted-by":"publisher","first-page":"110234","DOI":"10.1016\/j.biopha.2020.110234","volume":"127","author":"T Farkhondeh","year":"2020","unstructured":"Farkhondeh, T., Folgado, S. L., Pourbagher-Shahri, A. M., Ashrafizadeh, M. & Samarghandian, S. The therapeutic effect of resveratrol: focusing on the Nrf2 signaling pathway. Biomed. Pharmacother. 127, 110234 (2020).","journal-title":"Biomed. Pharmacother"},{"key":"11643_CR43","doi-asserted-by":"publisher","first-page":"1174867","DOI":"10.3389\/fphar.2023.1174867","volume":"14","author":"PP Patil","year":"2023","unstructured":"Patil, P. P. et al. Computational and experimental Pharmacology to Decode the efficacy of Theobroma cacao L. against doxorubicin-induced organ toxicity in EAC-mediated solid tumor-induced mice. Front. Pharmacol. 14, 1174867 (2023).","journal-title":"Front. Pharmacol."},{"issue":"1","key":"11643_CR44","doi-asserted-by":"publisher","first-page":"128","DOI":"10.3390\/ijms24010128","volume":"24","author":"VZ Lankin","year":"2022","unstructured":"Lankin, V. Z., Tikhaze, A. K. & Melkumyants, A. M. Malondialdehyde as an important key factor of molecular mechanisms of vascular wall damage under heart diseases development. Int. J. Mol. Sci. 24 (1), 128 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"11643_CR45","doi-asserted-by":"crossref","unstructured":"Islam, M. S. et al. In vivo anti-cancer activity of Basella alba leaf and seed extracts against Ehrlich\u2019s ascites carcinoma (EAC) cell line, Evidence-Based Complement. Altern. Med., vol. 2018. (2018).","DOI":"10.1155\/2018\/1537896"},{"issue":"12","key":"11643_CR46","doi-asserted-by":"publisher","first-page":"e0167536","DOI":"10.1371\/journal.pone.0167536","volume":"11","author":"AHMK Alam","year":"2016","unstructured":"Alam, A. H. M. K. et al. The antioxidative fraction of white mulberry induces apoptosis through regulation of p53 and NF\u03baB in EAC cells. PLoS One. 11 (12), e0167536 (2016).","journal-title":"PLoS One"},{"key":"11643_CR47","doi-asserted-by":"crossref","unstructured":"Aydin, S., Ugur, K., Aydin, S., Sahin & Yardim, M. Biomarkers in acute myocardial infarction: current perspectives. Vasc Health Risk Manag. 2 (15), 1\u201310 (2019).","DOI":"10.2147\/VHRM.S166157"},{"issue":"9","key":"11643_CR48","doi-asserted-by":"publisher","first-page":"9236","DOI":"10.1007\/s11356-019-06528-6","volume":"27","author":"E Tousson","year":"2020","unstructured":"Tousson, E., Hafez, E., Gazia, M. M. A., Salem, S. B. & Mutar, T. F. Hepatic ameliorative role of vitamin B17 against Ehrlich Ascites carcinoma\u2013induced liver toxicity. Environ. Sci. Pollut Res. 27 (9), 9236\u20139246 (2020).","journal-title":"Environ. Sci. Pollut Res."},{"key":"11643_CR49","unstructured":"El-Masry, T., Al-Shaalan, N., Tousson, E., Buabeid, M. & Al-Ghadeer, A. Potential therapy of vitamin B17 against Ehrlich solid tumor induced changes in interferon gamma, nuclear factor kappa B, DNA fragmentation, p53, Bcl2, survivin, VEGF and TNF-\u03b1 expressions in mice. Pak J. Pharm. Sci. 33, 393\u2013401 (2020)."},{"issue":"6","key":"11643_CR50","first-page":"2801","volume":"32","author":"TA El-Masry","year":"2019","unstructured":"El-Masry, T. A., Al-Shaalan, N. H., Tousson, E., Buabeid, M. & Alyousef, A. M. The therapeutic and antineoplastic effects of vitamin B17 against the growth of solid-form Ehrlich tumours and the associated changes in oxidative stress, DNA damage, apoptosis and proliferation in mice. Pak J. Pharm. Sci. 32 (6), 2801\u20132810 (2019).","journal-title":"Pak J. Pharm. Sci."},{"key":"11643_CR51","doi-asserted-by":"crossref","unstructured":"Khan, T. et al. Anti-cancer plants: A review of the active phytochemicals, applications in animal models, and regulatory aspects, Biomolecules, vol. 10, no. 1, p. 47, (2019).","DOI":"10.3390\/biom10010047"},{"key":"11643_CR52","doi-asserted-by":"crossref","unstructured":"Hare, J. M. Oxidative stress and apoptosis in heart failure progression, Circulation research, vol. 89, no. 3. Am Heart Assoc, pp. 198\u2013200, (2001).","DOI":"10.1161\/res.89.3.198"},{"issue":"2","key":"11643_CR53","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.jacc.2017.05.035","volume":"70","author":"T M\u00fcnzel","year":"2017","unstructured":"M\u00fcnzel, T. et al. Impact of oxidative stress on the heart and vasculature: part 2 of a 3-part series. J. Am. Coll. Cardiol. 70 (2), 212\u2013229 (2017).","journal-title":"J. Am. Coll. Cardiol."},{"key":"11643_CR54","doi-asserted-by":"crossref","unstructured":"Panth, N., Paudel, K. R. & Parajuli, K. Reactive oxygen species: a key hallmark of cardiovascular disease, Adv. Med., vol. 2016. (2016).","DOI":"10.1155\/2016\/9152732"},{"issue":"1","key":"11643_CR55","first-page":"29","volume":"35","author":"M Abbas","year":"2022","unstructured":"Abbas, M. & Mahmoud, A. H. Evaluation of antioxidant and Anti-tumor activities of Moringa extract in mice. Egypt. J. Radiat. Sci. Appl. 35 (1), 29\u201337 (2022).","journal-title":"Egypt. J. Radiat. Sci. Appl."},{"key":"11643_CR56","doi-asserted-by":"publisher","first-page":"105912","DOI":"10.1016\/j.phrs.2021.105912","volume":"173","author":"SK Goswami","year":"2021","unstructured":"Goswami, S. K., Ranjan, P., Dutta, R. K. & Verma, S. K. Management of inflammation in cardiovascular diseases. Pharmacol. Res. 173, 105912 (2021).","journal-title":"Pharmacol. Res."},{"issue":"24","key":"11643_CR57","doi-asserted-by":"publisher","first-page":"9739","DOI":"10.3390\/ijms21249739","volume":"21","author":"GA Cabral-Pacheco","year":"2020","unstructured":"Cabral-Pacheco, G. A. et al. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int. J. Mol. Sci. 21 (24), 9739 (2020).","journal-title":"Int. J. Mol. Sci."},{"issue":"11","key":"11643_CR58","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1161\/01.ATV.20.11.2394","volume":"20","author":"R Dewberry","year":"2000","unstructured":"Dewberry, R., Holden, H., Crossman, D. & Francis, S. Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis. Arterioscler. Thromb. Vasc Biol. 20 (11), 2394\u20132400 (2000).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"11643_CR59","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s00005-009-0024-y","volume":"57","author":"M Bujak","year":"2009","unstructured":"Bujak, M. & Frangogiannis, N. G. The role of IL-1 in the pathogenesis of heart disease. Arch. Immunol. Ther. Exp. (Warsz). 57, 165\u2013176 (2009).","journal-title":"Arch. Immunol. Ther. Exp. (Warsz)"},{"issue":"5","key":"11643_CR60","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.3892\/etm.2017.4246","volume":"13","author":"G Liu","year":"2017","unstructured":"Liu, G., Ma, C., Yang, H. & Zhang, P. Y. Transforming growth factor and its role in heart disease. Exp. Ther. Med. 13 (5), 2123\u20132128 (2017).","journal-title":"Exp. Ther. Med."},{"issue":"2","key":"11643_CR61","doi-asserted-by":"publisher","first-page":"195","DOI":"10.7150\/ijbs.8.195","volume":"8","author":"E Pardali","year":"2012","unstructured":"Pardali, E. & Ten Dijke, P. TGF signaling and cardiovascular diseases. Int. J. Biol. Sci. 8 (2), 195 (2012).","journal-title":"Int. J. Biol. Sci."},{"issue":"3","key":"11643_CR62","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.ajpath.2011.11.007","volume":"180","author":"S Gaspar-Pereira","year":"2012","unstructured":"Gaspar-Pereira, S. et al. The NF- B subunit c-Rel stimulates cardiac hypertrophy and fibrosis. Am. J. Pathol. 180 (3), 929\u2013939 (2012).","journal-title":"Am. J. Pathol."},{"issue":"5","key":"11643_CR63","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1161\/CIRCRESAHA.108.189746","volume":"104","author":"L Timmers","year":"2009","unstructured":"Timmers, L. et al. Targeted deletion of nuclear factor B p50 enhances cardiac remodeling and dysfunction following myocardial infarction. Circ. Res. 104 (5), 699\u2013706 (2009).","journal-title":"Circ. Res."},{"issue":"3","key":"11643_CR64","doi-asserted-by":"publisher","first-page":"H1337","DOI":"10.1152\/ajpheart.01175.2005","volume":"291","author":"S Kawano","year":"2006","unstructured":"Kawano, S. et al. Blockade of NF- B improves cardiac function and survival after myocardial infarction. Am. J. Physiol. Circ. Physiol. 291 (3), H1337\u2013H1344 (2006).","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"11643_CR65","doi-asserted-by":"crossref","unstructured":"Li, J. et al. p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities, Proc. Natl. Acad. Sci., vol. 116, no. 39, pp. 19626\u201319634, (2019).","DOI":"10.1073\/pnas.1904979116"},{"issue":"478","key":"11643_CR66","doi-asserted-by":"publisher","first-page":"eaau8866","DOI":"10.1126\/scitranslmed.aau8866","volume":"11","author":"B Saleme","year":"2019","unstructured":"Saleme, B. et al. Tissue-specific regulation of p53 by PKM2 is redox dependent and provides a therapeutic target for anthracycline-induced cardiotoxicity. Sci. Transl Med. 11 (478), eaau8866 (2019).","journal-title":"Sci. Transl Med."},{"issue":"4","key":"11643_CR67","doi-asserted-by":"publisher","first-page":"e0175195","DOI":"10.1371\/journal.pone.0175195","volume":"12","author":"A Riba","year":"2017","unstructured":"Riba, A. et al. Doxycycline protects against ROS-induced mitochondrial fragmentation and ISO-induced heart failure. PLoS One. 12 (4), e0175195 (2017).","journal-title":"PLoS One"},{"key":"11643_CR68","doi-asserted-by":"publisher","first-page":"105684","DOI":"10.1016\/j.jff.2023.105684","volume":"107","author":"Y Boshen","year":"2023","unstructured":"Boshen, Y. et al. Cardioprotective effects of amygdalin, a promising antioxidant, on acute myocardial infarction and underlying mechanisms. J. Funct. Foods. 107, 105684 (2023).","journal-title":"J. Funct. Foods"},{"key":"11643_CR69","doi-asserted-by":"publisher","unstructured":"Liczbi\u0144ski, P., Bukowska, B. Molecular mechanism of amygdalin action in vitro: review of the latest research. Immunopharmacol Immunotoxicol, 40 (3), 212\u2013218. https:\/\/doi.org\/10.1080\/08923973.2018.1441301 (2018).","DOI":"10.1080\/08923973.2018.1441301"},{"issue":"13","key":"11643_CR70","doi-asserted-by":"publisher","first-page":"10649","DOI":"10.3390\/ijms241310649","volume":"24","author":"S Moli\u00e8re","year":"2023","unstructured":"Moli\u00e8re, S., Jaulin, A., Tomasetto, C. L. & Dali-Youcef, N. Roles of matrix metalloproteinases and their natural inhibitors in metabolism: insights into health and disease. Int. J. Mol. Sci. 24 (13), 10649 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"11643_CR71","doi-asserted-by":"publisher","first-page":"110235","DOI":"10.1016\/j.cbi.2022.110235","volume":"369","author":"A Zhang","year":"2023","unstructured":"Zhang, A. et al. Amygdalin alleviated TGF- -induced epithelial-mesenchymal transition in bronchial epithelial cells. Chem. Biol. Interact. 369, 110235 (2023).","journal-title":"Chem. Biol. Interact."},{"key":"11643_CR72","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.2147\/JIR.S475347","volume":"17","author":"Q Zeng","year":"2024","unstructured":"Zeng, Q. et al. Amygdalin [corrigendum]elays cartilage [corrigendum]ndplate [corrigendum]egeneration and [corrigendum]mproves [corrigendum]ntervertebral [corrigendum]isc [corrigendum]egeneration by [corrigendum]nhibiting NF- B signaling pathway and [corrigendum]nflammatory [corrigendum]esponse [Corrigendum]. J. Inflamm. Res. 17, 2655\u20132656 (2024).","journal-title":"J. Inflamm. Res."},{"issue":"4","key":"11643_CR73","doi-asserted-by":"publisher","first-page":"486","DOI":"10.2174\/1871520620666200120095525","volume":"20","author":"MA El-Desouky","year":"2020","unstructured":"El-Desouky, M. A., Fahmi, A. A., Abdelkader, I. Y. & Nasraldin, K. M. Anti-cancer effect of amygdalin (Vitamin B-17) on hepatocellular carcinoma cell line (HepG2) in the presence and absence of zinc. Anti-Cancer Agents Med. Chem. (Formerly Curr. Med. Chem. Agents). 20 (4), 486\u2013494 (2020).","journal-title":"Anti-Cancer Agents Med. Chem. (Formerly Curr. Med. Chem. Agents)"},{"issue":"3","key":"11643_CR74","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1080\/08923973.2018.1441301","volume":"40","author":"P Liczbi\u0144ski","year":"2018","unstructured":"Liczbi\u0144ski, P. & Bukowska, B. Molecular mechanism of amygdalin action in vitro: review of the latest research. Immunopharmacol. Immunotoxicol. 40 (3), 212\u2013218 (2018).","journal-title":"Immunopharmacol. Immunotoxicol"},{"key":"11643_CR75","doi-asserted-by":"publisher","first-page":"613170","DOI":"10.3389\/fimmu.2020.613170","volume":"11","author":"K Pyrillou","year":"2020","unstructured":"Pyrillou, K., Burzynski, L. C. & Clarke, M. C. H. Alternative pathways of IL-1 activation, and its role in health and disease. Front. Immunol. 11, 613170 (2020).","journal-title":"Front. Immunol."},{"issue":"10","key":"11643_CR76","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1016\/j.intimp.2010.07.002","volume":"10","author":"JP Edwards","year":"2010","unstructured":"Edwards, J. P. & Emens, L. A. The multikinase inhibitor Sorafenib reverses the suppression of IL-12 and enhancement of IL-10 by PGE2 in murine macrophages. Int. Immunopharmacol. 10 (10), 1220\u20131228 (2010).","journal-title":"Int. Immunopharmacol."},{"key":"11643_CR77","unstructured":"Guadagni, F. et al. TNF\/VEGF cross-talk in chronic inflammation-related cancer initiation and progression: an early target in anti-cancer therapeutic strategy, In Vivo (Brooklyn)., vol. 21, no. 2, pp. 147\u2013161, (2007)."},{"issue":"8","key":"11643_CR78","doi-asserted-by":"publisher","first-page":"e0271631","DOI":"10.1371\/journal.pone.0271631","volume":"17","author":"D Zaafar","year":"2022","unstructured":"Zaafar, D., Khalil, H. M. A., Rasheed, R. A., Eltelbany, R. F. A. & Zaitone, S. A. Hesperetin mitigates sorafenib-induced cardiotoxicity in mice through Inhibition of the TLR4\/NLRP3 signaling pathway. PLoS One. 17 (8), e0271631 (2022).","journal-title":"PLoS One"},{"issue":"1","key":"11643_CR79","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1042\/BST20190357","volume":"48","author":"N Varej\u00e3o","year":"2020","unstructured":"Varej\u00e3o, N., Lascorz, J., Li, Y. & Reverter, D. Molecular mechanisms in SUMO conjugation. Biochem. Soc. Trans. 48 (1), 123\u2013135 (2020).","journal-title":"Biochem. Soc. Trans."},{"issue":"16","key":"11643_CR80","doi-asserted-by":"publisher","first-page":"4395","DOI":"10.1080\/07391102.2018.1552623","volume":"37","author":"VS Silva","year":"2019","unstructured":"Silva, V. S. et al. Thiophenacetamide as a potential modulator to NF-\u03baB: structure and dynamics study using in Silico and molecular biology assays. J. Biomol. Struct. Dyn. 37 (16), 4395\u20134406 (2019).","journal-title":"J. Biomol. Struct. Dyn."},{"issue":"4","key":"11643_CR81","doi-asserted-by":"publisher","first-page":"368","DOI":"10.22205\/sijbs\/2016\/v2\/i4\/103443","volume":"2","author":"M Serasanambati","year":"2016","unstructured":"Serasanambati, M. & Chilakapati, S. R. Function of nuclear factor kappa B (NF-kB) in human diseases-a review. South. Indian J. Biol. Sci. 2 (4), 368\u2013387 (2016).","journal-title":"South. Indian J. Biol. Sci."},{"issue":"10","key":"11643_CR82","doi-asserted-by":"publisher","first-page":"918","DOI":"10.2174\/1570159X18666200207120949","volume":"18","author":"S Singh","year":"2020","unstructured":"Singh, S. & Singh, T. G. Role of nuclear factor kappa B (NF-\u03baB) signalling in neurodegenerative diseases: an mechanistic approach. Curr. Neuropharmacol. 18 (10), 918\u2013935 (2020).","journal-title":"Curr. Neuropharmacol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11643-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11643-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11643-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:06:46Z","timestamp":1759244806000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-11643-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["11643"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-11643-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,30]]},"assertion":[{"value":"9 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experimental procedures follow Tanta University\u2019s animal care guidelines and the National Science Council\u2019s Guide for the Care and Use of Laboratory Animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33980"}}