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Current treatments mainly target differentiated hematopoietic progenitor cells, which may accelerate their depletion. Astragaloside IV (AS-IV), derived from Astragalus membranaceus, shows potential in hematopoiesis, but its direct effects on HSC remain unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The study employed both in vitro and in vivo approaches. In vitro experiments utilized K562 cells and mouse bone marrow nucleated cells (BMNCs) to evaluate AS-IV's effects on cell proliferation and mitochondrial function. In vivo studies involved a 4.0\u00a0Gy total body irradiation mouse model treated with different doses of AS-IV (50\u00a0mg\/kg and 100\u00a0mg\/kg). The mechanism of action was investigated through Western blot, flow cytometry, and metabolomics analyses. The AMPK\/PGC1\u03b1 pathway regulation was verified using AMPK inhibitors and mutant\u00a0plasmid, with molecular docking confirming AS-IV\u2019s direct binding to AMPK.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In vitro studies demonstrated that AS-IV significantly promoted the proliferation of K562 cells and BMNC while enhancing their mitochondrial membrane potential, mitochondrial mass, and ATP production. In the irradiated mouse model, AS-IV treatment led to significant improvements in peripheral blood cell counts, including white blood cells, red blood cells, and hemoglobin levels. Further investigation revealed that AS-IV increased the proportion of HSC in both bone marrow and spleen while improving their mitochondrial function. Transcriptomic sequencing and Western blot analysis identified the AMPK\/PGC1\u03b1 signaling pathway as the key mechanism  underlying AS-IV-mediated mitochondrial enhancement. These findings were validated through pharmacological inhibition of AMPK and AMPK<jats:sup>K45R<\/jats:sup> mutation experiments.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>AS-IV accelerates hematopoietic reconstruction following radiation injury via activation of the AMPK\/PGC1\u03b1 signaling pathway, which enhances HSC mitochondrial function.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13020-025-01092-3","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T18:05:10Z","timestamp":1743617110000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Astragaloside IV accelerates hematopoietic reconstruction by improving the AMPK\/PGC1\u03b1-mediated mitochondrial function in hematopoietic stem cells"],"prefix":"10.1186","volume":"20","author":[{"given":"Ling","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueying","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiesi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qibing","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalian","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9850-7576","authenticated-orcid":false,"given":"Anguo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feihong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"issue":"1","key":"1092_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21147\/j.issn.1000-9604.2017.01.01","volume":"29","author":"W Chen","year":"2017","unstructured":"Chen W, Zheng R, Zhang S, et al. 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