Yi-Jing Decoction Ameliorates Oligoasthenozoospermia by Inhibiting the Oxidative Stress-p38 Mitogen-Activated Protein Kinase-Mediated Mitochondrial Apoptosis Pathway in Leydig and Sertoli Cells

Background: To explore the therapeutic effects of Yi-jing decoction (YJD) on oxidative stress-induced oligoasthenozoospermia (OAZS) in mice, with a focus on its role in regulating mitochondrial apoptosis and testosterone synthesis. Methods: OAZS was induced in Bagg’s albino (BALB)/C mice by intraperitoneal injection of cyclophosphamide for 5 days, followed by oral administration of YJD at low (0.525 g/mL), medium (1.05 g/mL), and high (2.1 g/mL) doses for 5 weeks. A total of 75 mice were randomly divided into five groups: control, model, low-dose YJD, medium-dose YJD, and high-dose YJD. Sperm motility and count and sex hormone levels were measured, and testicular and epididymal tissues were analyzed using hematoxylin and eosin staining, transmission electron microscopy, and Western blotting to evaluate mitochondrial function, oxidative stress markers, and apoptosis-related protein expression. TM3 Leydig cells and primary Sertoli cells were used to assess the role of p38 mitogen-activated protein kinase (p38MAPK) in oxidative stress-induced apoptosis. Results: YJD significantly improved sperm motility and density and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone ( P < 0.05). Histological and ultrastructural analyses showed reduced mitochondrial damage and improved morphology of the seminiferous tubules in the YJD-treated groups. YJD downregulated the expression of apoptosis-related proteins (BCL2-Associated X [BAX], cytochrome complex [Cyt-C], caspase-3) and upregulated B-cell lymphoma 2 (Bcl-2), reducing the BAX/Bcl-2 ratio ( P < 0.05). Mitochondrial membrane potential was restored in the YJD groups. In TM3 and Sertoli cells, YJD inhibited the p38MAPK signaling pathway, preventing oxidative stress-induced mitochondrial apoptosis and enhancing the expression of the testosterone-synthesis enzymes steroidogenic acute regulatory protein (StAR) and P450scc. Conclusion: YJD effectively mitigates oxidative stress-induced spermatogenic dysfunction in OAZS by modulating the p38MAPK mitochondrial apoptosis pathway, improving mitochondrial function, and enhancing testosterone synthesis and utilization. These findings suggest that YJD is a potential therapeutic strategy for OAZS.