Qiangjing Tablets modulate oxidative stress and endoplasmic reticulum stress through the PI3K/Akt/NRF-2 signaling axis and regulate gut microbiota in ornidazole-induced asthenozoospermia rats.

BACKGROUND AND AIM: Asthenozoospermia (AZS) is a vital factor that causes male infertility. Qiangjing Tablets (QJT) is a Chinese medicine preparation that has good effects on improving kidney function and sperm motility. Although the effect of QJT on the AZS has been confirmed, its mechanism has not been completely elucidated. This study aimed to investigate the therapeutic effect of QJT on ornidazole (ORN) -induced AZS rats and its mechanism. EXPERIMENTAL PROCEDURE: ORN was used to establish an AZS rat's model. QJT and LY294002 (PI3K inhibitor) were supplied to the ORN-induced rats. H&E staining, ELISA, Western blot, and 16S rRNA sequencing were performed. RESULTS: Activating transcription factor 6 (ATF6), C/EBP-homologous protein (CHOP), PKR-like endoplasmic reticulum kinase (PERK), and p-PERK levels were enhanced in the ORN-treated rats, which were increased with the LY294002 administration. The opposite results were observed in PI3K, p-PI3K, Akt, p-Akt, HO-1, and Nrf-2 levels. QJT treatment improved the pathological manifestations, oxidative stress and ER stress, and enhanced the expressions of PI3K, p-PI3K, Akt, and p-Akt. ORN induced a decrease in the Firmicutes/Bacteroidetes ratio at the phylum level, which were reversed by QJT; while QJT regulates the relative abundance of Spirochaetes, Proteobacteria, Actinobacteria, Lactobacillus, Treponema, etc. QJT also modulates metabolic pathways, including carbohydrate metabolism, amino acid metabolism, lipid metabolism, and signal transduction. CONCLUSIONS: QJT modulated oxidative stress and ER stress via the PI3K/Akt/NRF-2 signaling axis and maintained gut microbiota homeostasis in AZS rats. This study will lay a theoretical basis for the treatment of AZS and male fertility.