Work

Astragaloside IV attenuates ferroptosis-related testicular injury in rats with experimental varicocele

Year: 2026

Type: article

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.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1893309