{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:49:53Z","timestamp":1791355793012,"version":"4.3.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Varicocele is an important correctable cause of male infertility. Oxidative stress and lipid peroxidation contribute to the associated testicular injury, but the role of ferroptosis remains controversial. Astragaloside IV (AS-IV), a quality-control metabolite of Astragali radix, has antioxidant activity and can modulate ferroptosis-related processes, yet its effect in varicocele is unclear. This study evaluated whether AS-IV attenuates testicular injury in experimental varicocele and examined ferroptosis-related mechanisms. A Sprague\u2013Dawley rat model was established by partial ligation of the left renal vein and treated with oral AS-IV; Ferrostatin-1 served as a pharmacological comparator. Label-free proteomics, histopathology, biochemical assays and targeted molecular analyses were combined with a TM4 Sertoli-cell model of RSL3-induced injury. AS-IV lessened tubular injury and improved Johnsen scores in a dose-related manner, reduced testicular Fe\n                    <jats:sup>2+<\/jats:sup>\n                    , ROS and MDA, and raised the GSH\/GSSG ratio. Proteomics showed partial reversal of lipid-metabolism and ferroptosis-related enrichment after AS-IV. These changes were accompanied by recovery of androgen receptor (AR) and MBOAT2. In TM4 cells, AS-IV improved viability and lowered C11-BODIPY oxidation after RSL3; enzalutamide weakened the effects of AS-IV on lipid peroxidation and MBOAT2 and only partly reduced the viability rescue. The findings provide experimental evidence that AS-IV ameliorates varicocele-related testicular injury and that AR\/MBOAT2-related signalling may participate.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1893309","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:53:22Z","timestamp":1791352402000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Astragaloside IV attenuates ferroptosis-related testicular injury in rats with experimental varicocele"],"prefix":"10.3389","volume":"17","author":[{"given":"Boxian","family":"Gao","sequence":"first","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjing","family":"Liu","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences Xiyuan Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxin","family":"Sun","sequence":"additional","affiliation":[{"name":"Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuozhuo","family":"Shi","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jixiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongfu","family":"Zhong","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.3390\/nu12051536","article-title":"Nutraceutical effects of lycopene in experimental varicocele: an \u201cin vivo\u201d model to study male infertility","volume":"12","author":"Antonuccio","year":"2020","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s00018-019-03253-8","article-title":"Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management","volume":"77","author":"Barati","year":"2020","journal-title":"Cell. 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