Oligoasthenozoospermia (OAS) is the most common type of semen abnormality in male infertility patients, and its incidence has been increasing in recent years [1], [2]. This situation poses a major challenge to male reproductive health and adversely affects the quality of family life. There is evidence of a close association between oxidative stress and sperm quality. Antioxidant therapy is effective in the treatment of male infertility [3], [4]. At present, the clinical treatment options mainly include drug therapy and surgical intervention [5], [6], [7]. However, these approaches often have limited efficacy and potential side effects. Therefore, there is an urgent need to explore new therapeutic strategies to improve the reproductive function of patients with azoospermia.

Guilu-Erxian-Glue (GLEXG) is a traditional Chinese medicine formula used to improve male reproductive dysfunction. Previous studies have found that GLEXG alleviates OAS induced by tripterygium wilfordii polyglycosides (GTW) in rats by antiferroptosis [8]. Ginseng and wolfberry are important components of Guilu Erxian gum [9]. In recent years, studies have found that traditional Chinese medicine monomers can be targeted to improve testicular function, and their single composition, clear efficacy, low price, few side effects and other characteristics have obvious advantages in the treatment of testicular injury [10], [11], [12]. Therefore, the individual monomers of ginseng and Lycium barbarum may also have great therapeutic potential.

Ginsenoside Rb1 (GRb1) is one of the main active components extracted from ginseng [13]. Studies have reported that GRb1 can reduce oxidative stress injury and improve pulmonary inflammation in streptozotocin-induced diabetic rats [14]. GRb1 prevents deoxynivalenol-induced immune injury by reducing oxidative stress and apoptosis in mice [15]. However, the study of GRb1 in OAS remains unreported. In addition, Lycium barbarum polysaccharide (LBP) has protective effects against oxidative damage in many cells and tissues [16]. According to the study of Liu et al., LBP has been shown to exhibit protective effects on retinal ganglion cells against apoptosis through the mitigation of mitochondrial membrane potential and reactive oxygen species [17]. It is worth mentioning that combination therapy is an important treatment for a variety of diseases, such as diabetic nephropathy [18] and renal cell carcinoma [19]. Portulacae Herba and Granati Pericarpium pair is a traditional Chinese herbal medicine treatment for colitis, clinically demonstrating a relatively favorable effect on relieving diarrhea and abnormal stools [20]. The study by Lu et al. showed that the synergistic effect of ginseng and Salvia miltiorrhiza significantly reduced tumor metastasis compared with drug monomers. Among them, the combination of RG1 and Cryptanshinone, the main active ingredients of the two drugs, also reduced tumor metastasis in vivo [21]. Based on the above research background, we hypothesized that the combination of GRb1 and LBPs might alleviate OAS through the anti-oxidative stress pathway.

Zinc is an essential trace element in the human body. Zinc in adult males promotes hormone synthesis and spermatogenesis, especially sperm motility [22], [23]. Oral administration of the antioxidant zinc can improve sperm number, motility, morphology, and pregnancy success rates in infertile men diagnosed with idiopathic oligoasthenospermia [24]. Zinc metabolism at the cellular level is essential for many biological processes in the body [25]. Zn-sucrose complex promotes the absorption of zinc in vivo by up-regulating the expression of genes related to intestinal zinc transport [26]. However, current reports lack a comprehensive understanding of the specific molecular pathways involved.

In this study, we established in vivo and in vitro OAS models induced by GTW and H2O2, respectively. GRb1 and LBP were then used to intervene in the OAS model to further elucidate the exact role of these compounds in the treatment of OAS and their potential as novel therapeutic agents.