Astragalin alleviates oligoasthenospermia via promoting nuclear translocation of Nrf2 and reducing ferroptosis of testis.

Oligoasthenospermia (OAS) is a global human developmental disease and the most common type of male infertility. There are currently no sufficiently effective therapeutic strategies for OAS. Pill (WZYZP) is a traditional Chinese prescription for the clinical treatment of male infertility, and its efficacy is well known in China. Therefore, due to the complexity of traditional Chinese medicine, the specific mechanism of action of WZYZP on OAS has not been elucidated. Astragalin (AG), one of the main active substances in WZYZP, has good antioxidant effect. The aim of this research is to investigate whether AG, the active substance in WZYZP, can treat OAS by promoting Nrf2 nuclear translocation and inhibiting ferroptosis. The OAS model was established by intraperitoneal injection of cyclophosphamide, and the therapeutic effects of AG and WZYZP on OAS were evaluated by detecting sperm quality, sex hormone levels and testicular pathological changes after intragastric administration of AG and WZYZP. Western blot was used to measure the expression levels of TFR1, SLC7A11, GPX4 and FTH1. The nuclear translocation of Nrf2 was detected by immunofluorescence staining and nuclear/intracellular expression of Nrf2. The results showed that AG could improve sperm quality and serum sex hormone levels in OAS rats, reduce the expression of testicular Fe and TFR1, up-regulate testicular SLC7A11, GPX4 and FTH1, and inhibit testicular ferroptosis. At the same time, AG can promote the expression and nuclear translocation of Nrf2 in the testis of OAS rats. AG can alleviate OAS via promoting nuclear translocation of Nrf2 and inhibiting ferroptosis of testis.