{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:08:56Z","timestamp":1790870936562,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bone marrow mesenchymal stem cells (BMSCs) are multipotent cells that play a critical role in bone formation and are vulnerable to oxidative stress\u2010induced dysfunction in osteoporosis (OP). This study investigates the pro\u2010osteogenic potential of ajugoside, a naturally occurring iridoid monoterpene from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Ajuga reptans<\/jats:italic>\n                    <\/jats:styled-content>\n                    , through a two\u2010phase experimental design involving both in\u00a0vitro and in\u00a0vivo models. In the in\u00a0vitro phase, an oxidative stress model was established in BMSCs using H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    , followed by ajugoside treatment or lentiviral overexpression of solute carrier family 5 member 1 (Slc5a1). Cell viability, osteogenic differentiation, oxidative stress,\u00a0and mitophagy were assessed. In the in\u00a0vivo phase, an ovariectomy\u2010induced OP mouse model was utilized to examine the therapeutic effects of ajugoside, resveratrol (a positive control), or adeno\u2010associated virus\u2010mediated Slc5a1 overexpression. Ajugoside inhibited Slc5a1 expression and activated AMPK signalling, leading to enhanced mitophagy and reduced oxidative stress. Ajugoside demonstrated a significant capacity to alleviate H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced injury in BMSCs, exhibiting a comparable mitigating effect on oxidative stress and mitophagy impairment in OP mice. However, the reactivation of Slc5a1 led to the reversal of these effects. Collectively, these findings demonstrate that ajugoside promotes osteogenic differentiation by suppressing Slc5a1 and activating AMPK\u2010mediated mitophagy, offering a promising therapeutic strategy for OP.\n                  <\/jats:p>","DOI":"10.1111\/1440-1681.70114","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:35:19Z","timestamp":1773005719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ajugoside Promotes the Repair of Osteoporotic Bone by Inducing Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells"],"prefix":"10.1111","volume":"53","author":[{"given":"Ruifeng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Orthopedics Lishui Municipal Central Hospital  Zhejiang P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Lishui Municipal Central Hospital  Zhejiang P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Lishui Municipal Central Hospital  Zhejiang P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifei","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Lishui Municipal Central Hospital  Zhejiang P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3886-571X","authenticated-orcid":false,"given":"Shuming","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Lishui Municipal Central Hospital  Zhejiang P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-024-02138-w"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-024-05301-x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-024-05287-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina57101119"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16035452"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12724"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2024.08.003"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2021.1851192"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26072893"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X19500137"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.1779"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-10769-w"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12070671"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-023-00489-y"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/19390211.2013.859213"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2009"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116505"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12096"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.31393"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bonr.2023.101664"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-024-01855-1"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-07527-x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13178"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7347"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.24272\/j.issn.2095-8137.2023.397"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15020276"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-024-00689-6"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjy052"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-021-01252-3"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.1c00207"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3FO01024D"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16954"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70288"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-024-05320-8"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115595"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2186112"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2020.12.235"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21705"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X18666200522202319"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.46627"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.70114","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1440-1681.70114","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.70114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:23:17Z","timestamp":1773804197000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.70114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/1440-1681.70114"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.70114","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70114"}}