{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:59:56Z","timestamp":1785387596021,"version":"3.55.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infancy, and propranolol is the first-line standard pharmacotherapy for high-risk IH. The clinically used formulation of propranolol is an equimolar 1:1 racemic mixture of two enantiomers, S-(\u2212)-propranolol and R-(+)-propranolol. The traditional mechanistic hypothesis is centered on the\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -adrenoceptor blockade pathway mediated by the S-enantiomer, yet this framework fails to fully explain the dose\u2013response relationship and long-term involution effect of propranolol in IH treatment. Recent studies have revealed that R-(+)-propranolol, which exhibits negligible\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -adrenoceptor blocking activity, exerts a remarkable and independent anti-IH effect, indicating the existence of a core\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -adrenoceptor-independent mechanism of action. This review systematically integrates the preclinical evidence for the \u03b2-independent anti-IH activity of R-(+)-propranolol, elucidates the discovery logic of SOX18 as the core molecular target, identifies key translational gaps (zero clinical trials, lack of infant enantiomer-specific PK data, chiral formulation challenges), and proposes a dual-track model of propranolol action in IH. The authors further clarify the critical gaps in clinical translation in this field and provide a theoretical basis for the precision therapy of IH and the development of novel chiral pharmaceuticals.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1863768","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:21:04Z","timestamp":1785385264000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["R-(+)-propranolol for infantile hemangioma: \u03b2-adrenoceptor-independent mechanisms and clinical translation prospects"],"prefix":"10.3389","volume":"13","author":[{"given":"Wei","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, China"]},{"name":"Department of Clinical Research Center of Vascular Abnormalities of Jiangxi Province","place":["Ganzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, China"]},{"name":"Department of Clinical Research Center of Vascular Abnormalities of Jiangxi Province","place":["Ganzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyang","family":"Zheng","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Gannan Medical University","place":["Ganzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, China"]},{"name":"Department of Clinical Research Center of Vascular Abnormalities of Jiangxi Province","place":["Ganzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Gannan Medical University","place":["Ganzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Center of Vascular Abnormalities of Jiangxi Province","place":["Ganzhou, China"]},{"name":"Jiangxi Provincial Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Hemangioma, Jiangxi University of Chinese Medicine","place":["Nanchang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, First Affiliated Hospital of Gannan Medical University","place":["Ganzhou, China"]},{"name":"Department of Clinical Research Center of Vascular Abnormalities of Jiangxi Province","place":["Ganzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1111\/j.1525-1470.2008.00626.x","article-title":"Infantile hemangiomas: how common are they? A systematic review of the medical literature","volume":"25","author":"Kilcline","year":"2008","journal-title":"Pediatr Dermatol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.det.2022.06.004","article-title":"Infantile hemangiomas","volume":"40","author":"Hasbani","year":"2022","journal-title":"Dermatol Clin"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3261","DOI":"10.21037\/tp-21-554","article-title":"Development and validation of psychological status questionnaire for parents of infantile hemangiomas","volume":"10","author":"Peng","year":"2021","journal-title":"Transl Pediatr"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0140-6736(16)00645-0","article-title":"Infantile 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Pharmacol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00431-015-2570-0","article-title":"Treatment of infantile haemangiomas: recommendations of a European expert group","volume":"174","author":"Hoeger","year":"2015","journal-title":"Eur J Pediatr"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1097\/PRS.0b013e31821b63a0","article-title":"Pharmacologic therapies for infantile hemangioma: is there a rational basis?","volume":"128","author":"Itinteang","year":"2011","journal-title":"Plast Reconstr Surg"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1111\/bjd.13048","article-title":"Propranolol targets the contractility of infantile haemangioma-derived pericytes","volume":"171","author":"Lee","year":"2014","journal-title":"Br J Dermatol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s10456-026-10057-5","article-title":"HDAC inhibition reprograms stem cell fate 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