{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:30:50Z","timestamp":1787956250316,"version":"build-2784847793"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"TALENTA USU 2022"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Doxorubicin (DOX) has been extensively utilized in cancer treatment. However, DOX administration has adverse effects, such as cardiac injury. This study intends to analyze the expression of TGF, cytochrome c, and apoptosis on the cardiac histology of rats induced with doxorubicin, since the prevalence of cardiotoxicity remains an unpreventable problem due to a lack of understanding of the mechanism underlying the cardiotoxicity result. Vernonia amygdalina ethanol extract (VAEE) was produced by soaking dried Vernonia amygdalina leaves in ethanol. Rats were randomly divided into seven groups: K- (only given doxorubicin 15 mg\/kgbw), KN (water saline), P100, P200, P400, P4600, and P800 (DOX 15 mg\/kgbw + 100, 200, 400, 600, and 800 mg\/kgbw extract); at the end of the study, rats were scarified, and blood was taken directly from the heart; the heart was then removed. TGF, cytochrome c, and apoptosis were stained using immunohistochemistry, whereas SOD, MDA, and GR concentration were evaluated using an ELISA kit. In conclusion, ethanol extract might protect the cardiotoxicity produced by doxorubicin by significantly reducing the expression of TGF, cytochrome c, and apoptosis in P600 and P800 compared to untreated control K- (p &lt; 0.001). These findings suggest that Vernonia amygdalina may protect cardiac rats by reducing the apoptosis, TGF, and cytochrome c expression while not producing the doxorubicinol as doxorubicin metabolite. In the future, Vernonia amygdalina could be used as herbal preventive therapy for patient administered doxorubicin to reduce the incidence of cardiotoxicity.<\/jats:p>","DOI":"10.3390\/molecules28114305","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T02:30:06Z","timestamp":1684981806000},"page":"4305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Vernonia amygdalina Ethanol Extract Protects against Doxorubicin-Induced Cardiotoxicity via TGF\u03b2, Cytochrome c, and Apoptosis"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2016-0151","authenticated-orcid":false,"given":"Rony Abdi","family":"Syahputra","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urip","family":"Harahap","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahdiana","family":"Harahap","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universitas Indonesia, Depok 16424, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andayana Puspitasari","family":"Gani","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aminah","family":"Dalimunthe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan 20155, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0503-4045","authenticated-orcid":false,"given":"Amer","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Biotechnology and Environment, University of Bari, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8559-9224","authenticated-orcid":false,"given":"Satirah","family":"Zainalabidin","sequence":"additional","affiliation":[{"name":"Biomedical Science, Centre of Toxicology and Health Risk Study, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.toxlet.2019.02.013","article-title":"Oxidative stress injury in doxorubicin-induced cardiotoxicity","volume":"307","author":"Mei","year":"2019","journal-title":"Toxicol. 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