Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models
Introductionβ-thalassemia is a genetic hemoglobinopathy characterized by defective β-globin synthesis and ineffective erythropoiesis. Pharmacological induction of fetal hemoglobin (HbF) via γ-globin gene activation represents a promising therapeutic strategy. Total ginsenosides (TG), the principal a...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1578237/full |
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| author | Dongling Cai Dongling Cai Dongling Cai Ying Chan Guangyu He Yamin Kong Yamin Kong Yamin Kong Aiqi Cai Aiqi Cai Aiqi Cai Yan Guo Yan Guo Baosheng Zhu Baosheng Zhu Baosheng Zhu |
| author_facet | Dongling Cai Dongling Cai Dongling Cai Ying Chan Guangyu He Yamin Kong Yamin Kong Yamin Kong Aiqi Cai Aiqi Cai Aiqi Cai Yan Guo Yan Guo Baosheng Zhu Baosheng Zhu Baosheng Zhu |
| author_sort | Dongling Cai |
| collection | DOAJ |
| description | Introductionβ-thalassemia is a genetic hemoglobinopathy characterized by defective β-globin synthesis and ineffective erythropoiesis. Pharmacological induction of fetal hemoglobin (HbF) via γ-globin gene activation represents a promising therapeutic strategy. Total ginsenosides (TG), the principal active constituents of Panax ginseng, have shown epigenetic and transcriptional modulatory properties, yet their role in HbF induction remains unexplored.MethodsWe evaluated the HbF-inducing potential of TG using human erythroleukemia cell line (K562), primary erythroid precursor cells (ErPCs) derived from CD34+ umbilical cord blood, and Townes transgenic mice. TG was administered at varying concentrations in vitro (25–400 μg/mL) and in vivo (50–800 mg/kg/day for 14 days). HbF and γ-globin expression were quantified by flow cytometry, immunofluorescence, and RT-qPCR. Hemoglobin content, cell viability, and hepatic histology were also assessed.ResultsTG significantly induced HbF production and γ-globin gene expression in both cellular models in a dose-dependent manner. In K562 cells, 200 μg/mL TG elevated γ-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.DiscussionThese findings establish TG as a potent, well-tolerated inducer of HbF through transcriptional activation of the γ-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 β-thalassemia. |
| format | Article |
| id | doaj-art-ff35b379b8bf4991a83622823de75c39 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-ff35b379b8bf4991a83622823de75c392025-08-21T05:27:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.15782371578237Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia modelsDongling Cai0Dongling Cai1Dongling Cai2Ying Chan3Guangyu He4Yamin Kong5Yamin Kong6Yamin Kong7Aiqi Cai8Aiqi Cai9Aiqi Cai10Yan Guo11Yan Guo12Baosheng Zhu13Baosheng Zhu14Baosheng Zhu15Department of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People’s Hospital of Yunnan Province, Kunming, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming, ChinaSchool of Life Sciences, Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People’s Hospital of Yunnan Province, Kunming, ChinaDepartment of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People’s Hospital of Yunnan Province, Kunming, ChinaDepartment of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People’s Hospital of Yunnan Province, Kunming, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming, ChinaSchool of Life Sciences, Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People’s Hospital of Yunnan Province, Kunming, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming, ChinaSchool of Life Sciences, Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People’s Hospital of Yunnan Province, Kunming, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming, ChinaDepartment of Medical Genetics, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, The First People’s Hospital of Yunnan Province, Kunming, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming, ChinaSchool of Life Sciences, Kunming University of Science and Technology, Kunming, Yunnan, ChinaIntroductionβ-thalassemia is a genetic hemoglobinopathy characterized by defective β-globin synthesis and ineffective erythropoiesis. Pharmacological induction of fetal hemoglobin (HbF) via γ-globin gene activation represents a promising therapeutic strategy. Total ginsenosides (TG), the principal active constituents of Panax ginseng, have shown epigenetic and transcriptional modulatory properties, yet their role in HbF induction remains unexplored.MethodsWe evaluated the HbF-inducing potential of TG using human erythroleukemia cell line (K562), primary erythroid precursor cells (ErPCs) derived from CD34+ umbilical cord blood, and Townes transgenic mice. TG was administered at varying concentrations in vitro (25–400 μg/mL) and in vivo (50–800 mg/kg/day for 14 days). HbF and γ-globin expression were quantified by flow cytometry, immunofluorescence, and RT-qPCR. Hemoglobin content, cell viability, and hepatic histology were also assessed.ResultsTG significantly induced HbF production and γ-globin gene expression in both cellular models in a dose-dependent manner. In K562 cells, 200 μg/mL TG elevated γ-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.DiscussionThese findings establish TG as a potent, well-tolerated inducer of HbF through transcriptional activation of the γ-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 β-thalassemia.https://www.frontiersin.org/articles/10.3389/fphar.2025.1578237/fullβ-thalassemiafetal hemoglobinreactivationγ-globin genetotal ginsenosides |
| spellingShingle | Dongling Cai Dongling Cai Dongling Cai Ying Chan Guangyu He Yamin Kong Yamin Kong Yamin Kong Aiqi Cai Aiqi Cai Aiqi Cai Yan Guo Yan Guo Baosheng Zhu Baosheng Zhu Baosheng Zhu Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models Frontiers in Pharmacology β-thalassemia fetal hemoglobin reactivation γ-globin gene total ginsenosides |
| title | Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models |
| title_full | Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models |
| title_fullStr | Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models |
| title_full_unstemmed | Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models |
| title_short | Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models |
| title_sort | total ginsenosides enhance γ globin expression and fetal hemoglobin production in β thalassemia models |
| topic | β-thalassemia fetal hemoglobin reactivation γ-globin gene total ginsenosides |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1578237/full |
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