Objective To explore the differential attenuation effects of Nüzhenzi (Ligustri Lucidi Fructus) and its wine-processed product on Tripterygium wilfordii polycoride (TWP)-induced reproductive toxicity, and to investigate its attenuation mechanism based on nuclear factor erythroid 2-related factor 2 (Nrf2) mediated testicular antioxidant defense. Methods ICR mice were ig TWP (40 mg/kg) for 28 d, and intervention was also given with Ligustri Lucidi Fructus or its wine-processed products. Reagent kits were used to detect the levels of testosterone in serum and oxidative stress-related indicators in testicular tissue. Hematoxylin-eosin (HE) staining was used to observe pathological changes in testicular tissue. Western blotting and qRT-PCR were used to detect the protein and mRNA expressions of Nrf2, heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1) in testicular tissue. Results TWP caused a loose structure of seminiferous tubules in testes of mice, a decrease in level of spermatogenic cells, a significant reduction in number of mature sperm, a significant decrease in testosterone levels (P < 0.01), and a significant increase in the level of malondialdehyde (MDA), a lipid peroxidation product in testes (P < 0.01). Ligustri Lucidi Fructus (1, 2 g/kg) could significantly inhibit the abnormal indicators mentioned above (P < 0.05, 0.01), and Ligustri Lucidi Fructus (2 g/kg) could also significantly enhance the activity of antioxidant enzymes (P < 0.05, 0.01). Ligustri Lucidi Fructus wine-processed products (1, 2 g/kg) could significantly inhibit the abnormal indicators mentioned above (P < 0.01), and Ligustri Lucidi Fructus wine-processed products (2 g/kg) could more comprehensively reverse oxidative stress imbalance (P < 0.01). At the same dose, the detoxification effect of Ligustri Lucidi Fructus wine-processed products was significantly better than that of their raw products (P < 0.05, 0.01). Mechanism analysis revealed that TWP significantly down-regulated the expressions of Nrf2 and its downstream molecules HO-1 and NQO1 in testicular tissue of mice (P < 0.01), while Ligustri Lucidi Fructus and its wine-processed products (1, 2 g/kg) significantly up-regulated the expressions of Nrf2 and its downstream molecules HO-1 and NQO1 (P < 0.05, 0.01), with Ligustri Lucidi Fructus wine-processed products showing a significantly better effect than Ligustri Lucidi Fructus (P < 0.01). Conclusion Ligustri Lucidi Fructus and its wine-processed products could alleviate the testicular reproductive toxicity caused by TWP, and the detoxification effect of wine-processed products is significantly better than that of raw products. The mechanism may be related to enhancing Nrf2 mediated testicular antioxidant defense.

Ligustri Lucidi Fructus  /  wine processing  /  reproductive toxicity  /  Nrf2  /  oxidative stress  /  specneuzhenide  /  salidroside