{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:46:02Z","timestamp":1792197962954,"version":"4.4.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"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. Pharmacol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>\u03b2-thalassemia is a genetic hemoglobinopathy characterized by defective \u03b2-globin synthesis and ineffective erythropoiesis. Pharmacological induction of fetal hemoglobin (HbF) via \u03b3-globin gene activation represents a promising therapeutic strategy. Total ginsenosides (TG), the principal active constituents of <jats:italic>Panax ginseng<\/jats:italic>, have shown epigenetic and transcriptional modulatory properties, yet their role in HbF induction remains unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated the HbF-inducing potential of TG using human erythroleukemia cell line (K562), primary erythroid precursor cells (ErPCs) derived from CD34<jats:sup>+<\/jats:sup> umbilical cord blood, and Townes transgenic mice. TG was administered at varying concentrations in vitro (25\u2013400 \u03bcg\/mL) and in vivo (50\u2013800 mg\/kg\/day for 14 days). HbF and \u03b3-globin expression were quantified by flow cytometry, immunofluorescence, and RT-qPCR. Hemoglobin content, cell viability, and hepatic histology were also assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TG significantly induced HbF production and \u03b3-globin gene expression in both cellular models in a dose-dependent manner. In K562 cells, 200 \u03bcg\/mL TG elevated \u03b3-globin mRNA by 4.29-fold; in ErPCs, the increase was 1.46-fold. HbF-positive cell populations rose markedly without impairing cell viability or morphology. In vivo, TG treatment at 200 and 400 mg\/kg led to 2.8- and 3.1-fold increases in F-cell proportions, respectively, surpassing hydroxyurea controls. No hepatotoxicity was observed upon histopathological examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings establish TG as a potent, well-tolerated inducer of HbF through transcriptional activation of the \u03b3-globin gene. Its efficacy across erythroid cell lines, primary progenitor cells, and transgenic mouse models underscores its translational potential as a natural therapeutic agent for \u03b2-thalassemia.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1578237","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T05:28:05Z","timestamp":1755754085000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Total ginsenosides enhance \u03b3-globin expression and fetal hemoglobin production in \u03b2-thalassemia models"],"prefix":"10.3389","volume":"16","author":[{"given":"Dongling","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiqi","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baosheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1080\/08880018.2017.1354948","article-title":"Hydroxyurea for lifelong transfusion-dependent \u03b2-thalassemia: a meta-analysis","volume":"34","author":"Algiraigri","year":"2017","journal-title":"Pediatr. 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