To investigate the mechanism of action of Wuzi Yanzong pill (WYP) in rats with oligoasthenozoospermia (OAZ) via metabolomics and to provide a possible basis for improving this WYP-based treatment.

A rat model of OAZ was established by treating male Sprague–Dawley rats with glucosides from Tripterygium wilfordii Hook. F. Seventy-two rats were randomly divided into six groups: control, L-carnitine (positive control), model, and low-, medium-, and high-dose WYP groups. Rats in the experimental groups were treated with WYP for 4 weeks. At the end of the treatment period, sperm cell quality (density, motility, and viability) was assessed using a semen analysis system, mitochondrial membrane potential (MMP) was assessed using flow cytometry, and testicular injury was assessed using hematoxylin and eosin staining to validate the therapeutic effect of WYP in OAZ. Further, serum metabolomics-based analysis was performed using high-performance liquid chromatography-mass spectrometry to identify differential metabolic pathways and possible mechanisms of action of WYP in OAZ treatment.

A rat model of OAZ was considered successfully-established after comparing the quality of spermatozoa in the model group to that in the control group. WYP-M and WYP-H treatments significantly improved sperm cell density, motility, and viability compared with those in the model group (all P <.05). Compared with the model group, both WYP-M and WYP-H treatments increased MMP values (P =.006 and P =.021 respectively), while there was no significant difference in the L-carnitine group. L-carnitine and WYP administration reversed damage to the testes to varying degrees compared with that in the model group. Further, 44 differential metabolites and four metabolic pathways, especially autophagy pathway, related to OAZ were identified via metabolomics.

WYP improves sperm cell quality and MMP in OAZ primarily via autophagy regulation. These findings can be employed to improve the efficacy of WYP in humans.

To investigate the therapeutic effects and pharmacological mechanisms of Yishen Xingyang capsule (YXC) in oligoasthenospermia (OA) rats.

Forty-eight male Sprague–Dawley rats were randomly divided into eight groups of six rats each: normal control (NC); model control (MC); three different positive drug (PD); and low-, medium-, and high-dose YXC groups. A rat model of OA was established by administering glucosides of Tripterygium wilfordii Hook. F (GTW). After YXC administration, penile erectile function was observed. The epididymis, blood, and testes of the rats were harvested for analysis of sperm quality, sex hormone levels, mitochondrial membrane potential, and the transforming growth factor (TGF)-β1/Smad signaling pathway.

Compared with that in the MC group, penile erectile function in the YXC groups and three PD groups increased (all P < .01). Moreover, sperm quality in the YXC groups and three PD groups improved (all P < .001). The levels of testosterone, follicle stimulating hormone, and luteinizing hormone in the three PD and YXC groups increased (all P < .05). The mitochondrial membrane potential in the three PD and YXC groups significantly improved (all P < .001). Furthermore, the YXC and three PD groups showed decreased TGF-β1 expression (all P < .05) compared with the MC group. The high-dose YXC group and three PD groups improved Smad2 and Smad4 expression (all P < .05).

YXC improved penile erectile function and sperm quality in OA rats, and the underlying mechanism included increase in sex hormones, inhibition of sperm apoptosis, and regulation of the TGF-β1/Smad signaling pathway. Meanwhile, this study provides a new effective drug option for the treatment of OA, which is beneficial to male reproductive health and social harmony.