{
  "abstract": "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–Dawley 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 ²⁺ , 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.",
  "abstract_shown": true,
  "affiliations": [
    "Shandong University of Traditional Chinese Medicine",
    "China Academy of Chinese Medical Sciences Xiyuan Hospital",
    "Shandong First Medical University",
    "Affiliated Hospital of Shandong University of Traditional Chinese Medicine"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Boxian Gao"
    },
    {
      "affs": [
        1
      ],
      "name": "Shengjing Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Mengxin Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Weiyi Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhuozhuo Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Jixiang Gao"
    },
    {
      "affs": [
        3
      ],
      "name": "Chongfu Zhong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2bhgf37a0s374.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1893309",
  "fulltext_url": "https://europepmc.org/articles/PMC13683633",
  "id": "2bhgf37a0s374",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1893309/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2743|Sperm and Testicular Function"
    ]
  ],
  "openalex": "W7220832373",
  "pdf_url": "https://europepmc.org/articles/PMC13683633?pdf=render",
  "pmcid": "PMC13683633",
  "pmid": "42908828",
  "published": "2026-10-07",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2bhgf37a0s374.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1893309",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1893309/full"
    },
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42908828",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42908828"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2743|Sperm and Testicular Function",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Astragaloside IV attenuates ferroptosis-related testicular injury in rats with experimental varicocele",
  "title_text": "Astragaloside IV attenuates ferroptosis-related testicular injury in rats with experimental varicocele",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:10Z",
  "url": "https://research.draconitic.com/paper/2bhgf37a0s374",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}