Inhibition of Bcl-2/Bax/cleaved caspase-3 pathway activity by rare ginsenosides ameliorates cyclophosphamide-induced oligoasthenospermia (OA) in male mice.

Abstract

Ethnopharmacological relevance: Oligoasthenozoospermia (OA) is the main factor leading to male infertility. According to traditional Chinese medicine, ginseng and its derivatives can improve male sperm quality by nourishing the kidneys and replenishing qi. Ginsenosides have been recognized as the principal pharmacologically active constituents of Panax ginseng, and are generally categorized into highly polar and rare ginsenosides. Rare ginsenosides can be generated through thermal transformation of the highly polar forms, yielding structurally related compounds collectively referred to as heat-transformed saponins (HTS). HTS comprising Rg6, F4, Rg3, Rk1, and Rg5-demonstrate substantial bioactivity at a dose of 50 mg/kg without observable toxicity. However, their effects on oligoasthenospermia (OA) and the associated molecular mechanisms remain poorly defined.

Aim of this study: To determine whether HTS can mitigate sperm damage caused by cyclophosphamide (CP) and elucidate their potential mechanism of action.

Materials and methods: Rare ginsenosides (HTS) were prepared in our laboratory. CP was used to construct an OA model. HTS were either administered prior to CP modelling to create a prevention group (HTS-CP) or after CP modelling to create a treatment group (CP-HTS). The intervention effect of HTS was evaluated using indicators such as sperm quality, hormone levels, and the degree of inflammation.

Results: In this study, HTS significantly increased the sperm count, improved sperm motility, and ameliorated testicular tissue damage. HTS decreased the elevation in follicle-stimulating hormone (FSH), lactate dehydrogenase (LDH), malondialdehyde (MDA), and inflammatory factor levels caused by CP and increased the levels of testosterone (T), luteinizing hormone (LH), acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase (SOD), and glutathione peroxidase (GSH) in the model group. HTS significantly increased the gene and protein expression levels of PUMA and Bcl-2 in testicular tissue and significantly decreased the gene and protein expression levels of Bax and caspase-3.

Conclusion: This study revealed that HTS can effectively ameliorate CP-induced damage to male sperm by inhibiting apoptosis via the Bcl-2/Bax/cleaved caspase-3 pathway.