{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:35:17Z","timestamp":1777624517194,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3500100"],"award-info":[{"award-number":["2022YFC3500100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82230126"],"award-info":[{"award-number":["82230126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20800"],"award-info":[{"award-number":["U24A20800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project of the Ministry of Science and Technology of China","doi-asserted-by":"publisher","award":["2023ZD0502600"],"award-info":[{"award-number":["2023ZD0502600"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014717","name":"National Science Fund for Excellent Young Scholars","doi-asserted-by":"publisher","award":["82222075"],"award-info":[{"award-number":["82222075"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory","award":["HQL2024PZ045"],"award-info":[{"award-number":["HQL2024PZ045"]}]},{"name":"Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory","award":["HQCML-C-2024003"],"award-info":[{"award-number":["HQCML-C-2024003"]}]},{"name":"National TCM Heritage and Innovation Team Project","award":["ZYYCXTD-C-202201"],"award-info":[{"award-number":["ZYYCXTD-C-202201"]}]},{"name":"Guangdong Provincial Key Laboratory of Syndrome and Formula","award":["2022B1212010012"],"award-info":[{"award-number":["2022B1212010012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Pressure overload-induced heart failure (HF) involves cardiac remodeling, ferroptosis, and impaired mitophagy. Yixinjiedu formula (YXJDF), a traditional Chinese medicine, shows cardiovascular protective effects, but its underlying mechanisms remain largely unclear. This study aims to evaluate the cardioprotective effect of YXJDF in pressure overload-induced HF and explore its regulatory role in ferroptosis and mitophagy. Methods: A transverse aortic constriction (TAC) mouse model and angiotensin II-induced HL-1 cardiomyocytes were used to assess the therapeutic effects of YXJDF. Cardiac function, ferroptosis, and mitophagy were evaluated using histological, biochemical, molecular, and imaging analyses. Autophagic flux was assessed using lysosomal inhibition. Network pharmacology was applied to identify potential targets, while LC-MS\/MS profiling and molecular docking were used to characterize major constituents of YXJDF and predict target interactions. Results: In TAC mice, YXJDF significantly improved cardiac function and attenuated myocardial hypertrophy and fibrosis. YXJDF suppressed ferroptotic injury, as evidenced by reduced lipid peroxidation, restoration of GPX4 and FTH1 expression, and normalization of antioxidant capacity. Mitophagy was restored, as indicated by increased PINK1 and Parkin expression, enhanced LC3-II accumulation, and reduced p62 and TOM20 levels, and as confirmed by autophagic flux analysis. Consistent protective effects on ferroptosis and mitophagy were observed in angiotensin II-induced cardiomyocytes. Network pharmacology analysis identified PINK1 as a key target, which was validated by in vivo and in vitro experiments. LC-MS\/MS identified 20 major chemical constituents in YXJDF, and molecular docking showed strong binding affinity between several compounds (e.g., calycosin, salvianolic acid A) and PINK1. Conclusions: YXJDF ameliorates pressure overload-induced cardiac injury by restoring PINK1\/Parkin-mediated mitophagy and suppressing ferroptosis. These findings reveal a multi-target mechanism underlying the therapeutic potential of YXJDF in HF.<\/jats:p>","DOI":"10.3390\/ph19030360","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T13:37:37Z","timestamp":1772026657000},"page":"360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Yixinjiedu Formula Attenuates Pressure Overload-Induced Cardiac Dysfunction by Suppressing Ferroptosis and Restoring Mitophagy via the PINK1\/Parkin Axis"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1390-1565","authenticated-orcid":false,"given":"Kang","family":"Xie","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Guangdong Provincial Key Laboratory of Syndrome and Formula, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2484-4235","authenticated-orcid":false,"given":"Haowen","family":"Zhuang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Dong","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4697-2647","authenticated-orcid":false,"given":"Yulin","family":"Ouyang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Guangdong Provincial Key Laboratory of Syndrome and Formula, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Syndrome and Formula, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongzheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8665-1351","authenticated-orcid":false,"given":"Jinhong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinmeng","family":"Teng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Guangdong Provincial Laboratory of Traditional Chinese Medicine, Hengqin, Zhuhai 519031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Guangdong Provincial Laboratory of Traditional Chinese Medicine, Hengqin, Zhuhai 519031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-2225","authenticated-orcid":false,"given":"Junyan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Writing Committee Members, and ACC\/AHA Joint Committee Members (2022). 2022 AHA\/ACC\/HFSA Guideline for the Management of Heart Failure. 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