Effect of stem extract of Schisandra Chinensis on improving spermatogenesis disorder induced by Cisplatin in Vivo and in Vitro

Background: The primary adverse effect of chemotherapy drugs is the induction of spermatogenic disorders. Schisandra chinensis (Turcz) Baill. have been preliminarily shown to have a significant ameliorative in spermatogenic disorders. Nevertheless, there are relatively few studies on non-medicinal parts such as stems of S. chinensis, which have good therapeutic potential for side effects caused by cisplatin. Up to now, a total of 238 compounds have been isolated and identified from the vine stem of S. chinensi. The main components are lignans, polysaccharides, volatile oils, and organic acids. Therefore, the development of S. chinensis stem as a source of a novel chemotherapy drug protector is of great significance. Methods: In the present study, we explored the protective effect of the stem extract of S. chinensis (SCE) against cisplatin-induced spermatogenic disorders and its possible molecular mechanisms in vitro and in vivo. The network pharmacology was used to predict the targets that may act on spermatogenic disorders. Mice were injected intraperitoneally with cisplatin at 2 mg/kg for 7 days to induce spermatogenic disorders. SCE (75, 150, and 300 mg/kg) was administered to mice by gavage for 21 days. TM3 cells were treated with Schisandrol B (Sol B) (0.5, 1, and 2 mu M) in the presence or absence of cisplatin (40 mu M), and then cell viability, oxidative stress, apoptosis, and mitochondrial function were evaluated. Results: 16 constituents and target proteins were predicted to have possible effects on spermatogenic disorders by network pharmacology. Both in vivo and in vitro experiments showed a favorable protective effect of SCE against cisplatin-induced spermatogenic disorders. Sol B might as the major chemical component is responsibility for the protective effect. The mechanism may involve the regulation of Nrf2\HO-1 protein, PI3K\Akt, apoptosis, and MAPK signaling pathway to modulate 17 beta HSD, cycp450, Star and other crucial proteins in the testosterone synthesis pathway. Ultimately, this regulatory process aims to ameliorate the disruption of sex hormone secretion by cisplatin. Conclusion: These results indicated that the lignans in SCE could effectively improve the spermatogenesis barrier caused by cisplatin. These findings provided a theoretical basis for the development of non-medicinal parts of S. chinensis, and laid a foundation for improving spermatogenesis disorders caused by chemotherapy drugs.