{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:02:27Z","timestamp":1779778947686,"version":"3.53.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["grant number 82300441"],"award-info":[{"award-number":["grant number 82300441"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cardiac hypertrophy drives heart failure progression, with cardiomyocyte apoptosis playing a central role. Platycodin D (PLD), a bioactive saponin derived from Platycodon grandiflorum, exhibits cardioprotective properties, but its therapeutic potential and mechanisms in heart failure remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we employed a mouse model of isoprenaline (ISO)-induced heart failure to investigate the therapeutic potential of PLD. Mice were administered PLD at doses of 12.5, 25, or 50\u00a0mg\/kg\/d for 4\u00a0weeks to evaluate its effects on cardiac function and hypertrophy. To elucidate the underlying mechanisms, we performed network pharmacology analysis, which identified p53 as a candidate target of PLD. The functional role of p53 was further assessed through pharmacological interventions, comparing the effects of PLD with those of the p53 inhibitor pifithrin-\u03b1 (PFT-\u03b1) and examining whether p53 activation could abrogate PLD-mediated cardioprotection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PLD dose-dependently improved cardiac function and attenuated cardiac hypertrophy in ISO-induced HF mice. Network pharmacology and molecular docking identified p53 as a direct binding partner of PLD. PLD alleviated the apoptosis of cardiomyocyte by inhibition p53 depended on Bcl-2\/Bax\/caspase-3 signaling pathway. The cardioprotective effects of PLD were comparable to those of the p53 inhibitor pifithrin-\u03b1 (PFT-\u03b1). But, these benefits were abolished upon p53 activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that PLD attenuates ISO-induced cardiac hypertrophy and heart failure by inhibiting the p53-mediated Bcl-2\/Bax\/caspase-3 apoptotic pathway. These findings establish PLD as a promising therapeutic candidate for heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1832803","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:04:22Z","timestamp":1779775462000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Platycodin D alleviates cardiac hypertrophy in the treatment of heart failure by inhibiting p53-dependent BCL-2\/Bax\/caspase-3 signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingrui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Intervention, Guiyang Public Health Treatment Center","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"113380","DOI":"10.1016\/j.expneurol.2020.113380","article-title":"TTDA inhibited apoptosis by regulating the p53-Bax\/Bcl2 axis in glioma","volume":"331","author":"Bai","year":"2020","journal-title":"Exp. 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