{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:02:16Z","timestamp":1785427336402,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"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":"crossref","award":["81903927"],"award-info":[{"award-number":["81903927"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["81903927"],"award-info":[{"award-number":["81903927"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Heart transplantation remains the definitive therapy for end-stage heart failure, but its success critically depends on optimal donor heart preservation. Although the University of Wisconsin (UW) solution is the clinical gold standard, its safe storage window for hearts is limited to 4\u20136 h. Extending this static cold storage (SCS) window represents a critical challenge. We hypothesized that Salvianolic acid B (SalB), a primary bioactive compound in Salvia miltiorrhiza with potent antioxidant and cardioprotective properties, could serve as an effective pharmacological additive to UW solution. Methods: Isolated mouse hearts were subjected to SCS at 4 \u00b0C for varying durations (4, 8, and 10 h) in either standard UW solution or UW solution supplemented with 0.8 mg\/mL SalB. Myocardial injury was assessed via cardiac enzyme leakage (BNP, CK-MB, LDH), oxidative stress markers, sterile inflammation, and histopathology. The regulatory roles of SalB on apoptosis and autophagic flux were further evaluated, utilizing the autophagy inhibitor 3-methyladenine (3-MA) to establish mechanistic causality. Results: Hearts preserved in SalB-supplemented UW solution exhibited significantly ameliorated histopathological damage, reduced cold ischemia-induced enzyme efflux, and suppressed oxidative stress compared to standard UW solution. Notably, hearts preserved for 8 h with SalB maintained structural and biochemical integrity comparable to those stored for only 4 h in standard UW solution. Mechanistic investigations revealed that SalB treatment orchestrates a pro-survival shift by significantly reducing cardiomyocyte apoptosis and robustly enhancing autophagic flux to maintain cellular homeostasis. The abrogation of autophagy by 3-MA effectively reversed these cardioprotective benefits. Conclusions: Supplementing UW solution with SalB effectively prolongs the structural and biochemical preservation of donor hearts during cold storage up to 8\u201310 h. By mitigating ischemia\u2013reperfusion injury via the targeted modulation of autophagic flux, SalB highlights its strong translational potential as a robust pharmacological additive for heart transplantation.<\/jats:p>","DOI":"10.3390\/ph19071082","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T01:05:58Z","timestamp":1784077558000},"page":"1082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salvianolic Acid B Preserves Myocardial Viability and Extends the Preservation Window of Mouse Hearts During Static Cold Storage"],"prefix":"10.3390","volume":"19","author":[{"given":"Junyi","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyi","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"602597","DOI":"10.1155\/2015\/602597","article-title":"Mesenchymal stromal cell therapy in ischemia\/reperfusion injury","volume":"2015","author":"Rowart","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Li, J., Peng, Q., Yang, R., Li, K., Zhu, P., Zhu, Y., Zhou, P., Szab\u00f3, G., and Zheng, S. (2021). Application of mesenchymal stem cells during machine perfusion: An emerging novel strategy for organ preservation. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.713920"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e202","DOI":"10.1097\/TP.0000000000003679","article-title":"Advances in Kidney Preservation Techniques and Their Application in Clinical Practice","volume":"105","author":"Hosgood","year":"2021","journal-title":"Transplantation"},{"key":"ref_4","first-page":"CD011671","article-title":"Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation","volume":"7","author":"Tingle","year":"2024","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e148","DOI":"10.1097\/TP.0000000000005185","article-title":"Investigating cardiac temperature during heart transplantation using the static cold storage paradigm","volume":"109","author":"Paez","year":"2025","journal-title":"Transplantation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1016\/j.cryobiol.2009.06.004","article-title":"Hypothermic organ preservation by static storage methods: Current status and a view to the future","volume":"60","author":"McAnulty","year":"2010","journal-title":"Cryobiology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Verstraeten, L., Den Abt, R., Ghesqui\u00e8re, B., and Jochmans, I. (2023). Current Insights into the Metabolome during Hypothermic Kidney Perfusion-A Scoping Review. J. Clin. Med., 12.","DOI":"10.3390\/jcm12113613"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/ajt.13062","article-title":"UW solution: Still the \u201cgold standard\u201d for liver transplantation","volume":"15","author":"Stewart","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e00978","DOI":"10.14309\/ctg.0000000000000978","article-title":"Machine Perfusion Ameliorates Nonanastomotic Strictures After Liver Transplantation: A Systematic Review and Meta-analysis of Randomized Controlled Trials","volume":"17","author":"Wang","year":"2026","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000499610","article-title":"Organ preservation into the 2020s: The era of dynamic intervention","volume":"46","author":"Petrenko","year":"2019","journal-title":"Transfus. Med. Hemother."},{"key":"ref_11","first-page":"149","article-title":"Research progress on the application and mechanism of traditional Chinese medicine in organ preservation solution","volume":"51","author":"Zhong","year":"2022","journal-title":"J. Med. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yang, S., Chen, H., Su, W., Luo, Y., Liao, J., Wang, Y., Xiong, L., Zhang, C., Li, F., and Chen, Z.-S. (2023). Protective effects of Salvianic acid A against multiple-organ ischemia-reperfusion injury: A review. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1297124"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106794","DOI":"10.1016\/j.fbio.2025.106794","article-title":"Salvianolic acid B ameliorates lipopolysaccharide-induced inflammatory liver injury via deacetylation of NF-\u03baB RelA","volume":"68","author":"Wang","year":"2025","journal-title":"Food Biosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121780","DOI":"10.1016\/j.jep.2026.121780","article-title":"Multitargeted synergistic mechanisms of Salvia miltiorrhiza and its bioactive compounds: A review","volume":"368","author":"Wang","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","first-page":"77","article-title":"Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia\/Reperfusion- and Lipopolysaccharide-Induced Disturbances: Mechanistic and Therapeutic Views","volume":"38","author":"Han","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_16","first-page":"1195","article-title":"Salvia polyphenolate reduces the intestinal ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress","volume":"38","author":"Li","year":"2021","journal-title":"Tianjin Univ. Tradit. Chin. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4925035","DOI":"10.1155\/mi\/4925035","article-title":"Research Progress on Salvia miltiorrhiza Bioactive Components Regulating P-Selectin for Microcirculatory Improvement: Potential Implications in Acute Pancreatitis","volume":"2026","author":"Liu","year":"2026","journal-title":"Mediat. Inflamm."},{"key":"ref_18","first-page":"727","article-title":"Effect and mechanism of Danshen injection in improving intestinal mucosal barrier function in rats with adhesive intestinal obstruction","volume":"34","author":"Zhou","year":"2025","journal-title":"Chin. J. Gen. Surg."},{"key":"ref_19","first-page":"74","article-title":"Research progress on chemical constituents and pharmacological effects of salvianolic acid B","volume":"48","author":"Ren","year":"2019","journal-title":"Shandong Chem. Ind."},{"key":"ref_20","first-page":"17","article-title":"Analysis of clinical significance of myocardial enzyme profiling in patients with acute myocardial infarction","volume":"21","author":"Zhang","year":"2021","journal-title":"Mod. Health"},{"key":"ref_21","first-page":"70","article-title":"Analysis of BNP, cTnI and myocardial enzyme index detection in the clinical diagnosis of patients with acute heart failure","volume":"50","author":"Sun","year":"2021","journal-title":"Heilongjiang J. Tradit. Chin. Med."},{"key":"ref_22","first-page":"28","article-title":"Correlation between the expression of proinflammatory factor and anti-inflammatory factor in peripheral blood of patients with sepsis and myocardial injury","volume":"47","author":"Li","year":"2020","journal-title":"Chin. J. Pract. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The biological basis for cardiac repair after myocardial infarction: From inflammation to fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bbamem.2017.05.018","article-title":"Intracellular trafficking pathways of Cx43 gap junction channels","volume":"1860","author":"Epifantseva","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_25","first-page":"1192","article-title":"Mechanism of salvianolic acid B activation of autophagy to improve calcification of vascular smooth muscle cells induced by high phosphorus","volume":"42","author":"Lin","year":"2022","journal-title":"Chin. J. Hosp. Pharm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.healun.2011.11.023","article-title":"A novel method of measuring cardiac preservation injury demonstrates University of Wisconsin solution is associated with less ischemic necrosis than Celsior in early cardiac allograft biopsy specimens","volume":"31","author":"George","year":"2012","journal-title":"J. Heart Lung Transplant."},{"key":"ref_27","first-page":"297","article-title":"Advancements in Donor Heart Preservation Methods: A Review of Approaches","volume":"42","author":"Hassanzadeh","year":"2026","journal-title":"Can. J. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.healun.2011.05.005","article-title":"Organ storage with University of Wisconsin solution is associated with improved outcomes after orthotopic heart transplantation","volume":"30","author":"George","year":"2011","journal-title":"J. Heart Lung Transplant."},{"key":"ref_29","first-page":"1143","article-title":"Preservation solutions for cardiac and pulmonary donor grafts: A review of the current literature","volume":"6","author":"Latchana","year":"2014","journal-title":"J. Thorac. Dis."},{"key":"ref_30","first-page":"449","article-title":"Advances in pharmacological effects of salvianolic acid B on cardiovascular diseases","volume":"31","author":"Lin","year":"2015","journal-title":"Chin. Pharmacol. Bull."},{"key":"ref_31","first-page":"501","article-title":"Protective effect of salvianolic acid B on isolated donor lung in rats","volume":"35","author":"Xu","year":"2014","journal-title":"Chin. J. Organ. Transplant."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.3892\/etm.2013.964","article-title":"Early diagnosis of rats with acute myocardial infarction by measurement of brain natriuretic peptide","volume":"5","author":"Li","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_33","first-page":"2048","article-title":"Protective Effect and Mechanism of Raffinose-low Potassium Dextran Added Salvianolic Acid B on Isolated Lung in Rats","volume":"15","author":"Sun","year":"2015","journal-title":"Prog. Mod. Biomed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/7\/1082\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:21:55Z","timestamp":1784175715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/7\/1082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":34,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ph19071082"],"URL":"https:\/\/doi.org\/10.3390\/ph19071082","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]}}}