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Rg1 alleviates oxidative stress and spermatogonium apoptosis in D-gal-induced testicular toxicity by activating Akt
Ziling Wang1, Kunhang Du1, Jiying Hou1
1Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing, People's Republic of China.
Abstract:
ABSTRACTObjectives: High reactive oxygen species (ROS) levels lead to cell death, and the testes are among the most vulnerable organs to oxidative damage. Rg1, an active ingredient extracted from the natural medicine ginseng, has potential anti-inflammatory, antioxidant and antiapoptotic properties. Our previous studies showed that Rg1 can effectively improve spermatogenic function in mice, but the specific mechanism remains unclear. The purpose of this study was to investigate the effect of Rg1 on oxidative stress and spermatogonium apoptosis in D-gal-induced testicular toxicity and elucidate the associated mechanism.Methods: Male C57BL/6 mice at 6-8 weeks of age were intraperitoneally injected with D-gal (200 mg/kg) for 42 days to establish a testicular injury model, and on day 16, 40 mg/kg Rg1-rich saline was injected intraperitoneally. Concurrently, we established an in vitro model of D-gal-damaged spermatogonia, which was treated with Rg1.Results: We found that treatment with the ginsenoside Rg1 reduced D-gal-induced oxidative stress and spermatogonium apoptosis in vivo and in vitro. Mechanistically, we found that Rg1 activated Akt/bad signaling and reduced D-gal-induced spermatogonium apoptosis.Discussion: We provide evidence showing that the antioxidant effect of Rg1 is mediated by the Akt/GSK-3β/NRF2 axis. Based on these findings, we consider Rg1 a potential treatment for testicular oxidative damage.
Insights
Ginsenoside Rg1 protects against testicular damage by reducing oxidative stress and cell death. This study reveals Rg1 activates key signaling pathways, offering a potential treatment for testicular oxidative injury.
Area of Science:
- Reproductive Biology
- Toxicology
- Pharmacology
Background:
- High reactive oxygen species (ROS) levels cause cell death, particularly in testes, which are vulnerable to oxidative damage.
- Ginsenoside Rg1, from ginseng, exhibits anti-inflammatory, antioxidant, and antiapoptotic properties.
- Previous studies indicated Rg1 improves spermatogenic function, but the mechanism was unclear.
Purpose of the Study:
- To investigate Rg1's effect on oxidative stress and spermatogonium apoptosis in D-galactose (D-gal)-induced testicular toxicity.
- To elucidate the underlying mechanism of Rg1's protective effects.
Main Methods:
- Established a D-gal-induced testicular injury model in male C57BL/6 mice.
- Treated mice and an in vitro model of D-gal-damaged spermatogonia with Rg1.
- Analyzed the activation of Akt/Bad signaling and the Akt/GSK-3β/NRF2 axis.
Main Results:
- Rg1 treatment significantly reduced D-gal-induced oxidative stress and spermatogonium apoptosis in both in vivo and in vitro models.
- Rg1 was found to activate Akt/Bad signaling, thereby reducing spermatogonium apoptosis.
- The antioxidant effect of Rg1 was mediated by the Akt/GSK-3β/NRF2 pathway.
Conclusions:
- Ginsenoside Rg1 demonstrates protective effects against D-gal-induced testicular toxicity.
- Rg1 mitigates oxidative stress and spermatogonium apoptosis via the Akt/GSK-3β/NRF2 signaling pathway.
- Rg1 is a potential therapeutic agent for testicular oxidative damage.
