Ginsenoside Rb1 combined with Lycium barbarum polysaccharide alleviate the Tripterygium wilfordii polyglycoside-induced oligoasthenozoospermia in mice by inhibiting ZnT3-mediated oxidative stress response

Abstract

Background

Oligoasthenozoospermia (OAS) is one of the main causes of male infertility. Studies have shown that ginsenoside Rb1 (GRb1) and Lycium barbarum polysaccharide (LBP) have great potential in treating OAS. This study aims to investigate the effects of combined GRb1 and LBP treatment on OAS and the underlying molecular mechanisms.

Methods

The Tripterygium wilfordii polyglycoside (GTW)-induced mouse model and H₂O₂-induced cell model were intervened with GRb1 and LBP. HE staining and Johnson score were used to evaluate the degree of testicular injury. Then, sperm quality was evaluated, and the levels of sperm-related hormones were measured. The regulatory effect of GRb1 and LBP on oxidative stress in OAS mice and cells was explored. In addition, total zinc content in testicular tissues and GC-2 cells was measured, and the mRNA and protein expression levels of zinc transporter 3 (ZnT3) were detected.

Results

In the OAS model of mice treated with GRb1 and LBP, the coefficient of testis and epididymis were increased, and the degree of damage and sperm quality were significantly improved. Serum levels of T, LH, and FSH were increased in mice. Moreover, inhibition of ZnT3 signaling increased total intracellular zinc content in GC-2 cells. Overexpression of ZnT3 reversed the inhibitory effects of the combination of GRb1 and LBP on oxidative stress and the therapeutic effects in OAS mice.

Conclusion

The combined treatment of GRb1 and LBP could inhibit oxidative stress response by down-regulating ZnT3 signaling, thereby improving OAS mice. This provided a new strategy for the drug treatment of OAS.