{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:57:03Z","timestamp":1793163423387,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"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":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endothelial dysfunction under high-glucose conditions is a key pathological process contributing to the development and progression of diabetic osteoporosis (DOP). High glucose-induced damage to H-type vascular endothelial cells (H-type ECs), including mitochondrial dysfunction, increased lipid peroxidation, and activation of ferroptosis, is considered a potential mechanism underlying bone loss and dysregulated bone metabolism in DOP. Diabetic osteoporosis is a common and severe complication in patients with diabetes, and current clinical treatment options remain limited. Ginsenoside Rg1 (Rg1), one of the main active components of ginseng, has been shown to possess antioxidant and anti-osteoporotic effects, but its underlying mechanisms in DOP remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, spontaneously diabetic GK rats and high-glucose-treated H-type ECs were used to establish\n                      <jats:italic>in vivo<\/jats:italic>\n                      diabetic osteoporosis models and\n                      <jats:italic>in vitro<\/jats:italic>\n                      cell models, respectively. The effects of Rg1 on bone loss in GK rats as well as on mitochondrial function and lipid peroxidation in H-type ECs were evaluated.\n                      <jats:italic>In vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments were conducted to investigate the potential mechanisms of Rg1 in regulating mitochondrial function and the SLC3A2\/SLC7A11-GPX4 signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our results showed that, compared with the model group, Rg1 at different doses effectively reduced systemic bone loss, with no significant difference between medium and high doses. Compared with the ferroptosis activator and inhibitor groups, Rg1 inhibited ferroptosis and promoted H-type vessel formation. Furthermore,\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments confirmed these findings and demonstrated that Rg1 activated the SLC3A2\/SLC7A11-GPX4 signaling pathway, while modulating H-type ECs mitochondrial membrane potential, decreasing mitochondrial reactive oxygen species (mtROS), and increasing lipid peroxidation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study demonstrated that Rg1 promotes vessel\u2013osteoblast coupling and regulates bone metabolism, thereby delaying the progression of diabetic osteoporosis (DOP). The underlying mechanism may involve activation of GPX4 expression in coordination with the regulation of H-type ECs mitochondrial membrane potential, leading to decreased mtROS levels and increased lipid peroxidation, ultimately intervening in ferroptosis. These findings highlight the GPX4\u2013mitochondria cooperative regulation of H-type ECs ferroptosis by Rg1 and provide a new potential avenue for DOP therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fragi.2026.1736263","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:38:23Z","timestamp":1773758303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Ginsenoside Rg1 antagonizes diabetic osteoporosis by regulating ferroptosis via mitochondrial membrane potential in H-type vascular endothelial cells"],"prefix":"10.3389","volume":"7","author":[{"given":"Mi","family":"Chen","sequence":"first","affiliation":[{"name":"School of Graduate, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Bai","sequence":"additional","affiliation":[{"name":"Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Graduate, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Pang","sequence":"additional","affiliation":[{"name":"School of Graduate, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Graduate, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxin","family":"Yi","sequence":"additional","affiliation":[{"name":"School of Graduate, Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Guangxi University of Chinese Medicine","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fnut.2023.1178573","article-title":"Iron metabolism and ferroptosis in diabetic bone loss: from mechanism to therapy","volume":"10","author":"Bao","year":"2023","journal-title":"Front. 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