Many routes have been explored to search for effective, safe, and affordable alternatives to hazardous female contraceptives. Herbal extracts and their secondary metabolites are some of the interesting research areas to address this growing issue. This study aims to investigate the effects of ten different plant extracts on testicular spermatogenesis. The correlation between the chemical profile of these extracts and their in vivo effect on male reproductive system was evaluated using various techniques. Approximately 10% of LD50 of hydro-methanolic extracts were orally administrated to rats for 60 days. Semen parameters, sexual organ weights, and serum levels of male sex hormones in addition to testes histopathology, were evaluated. Moreover, metabolomic analysis using (LC-HRESIMS), multivariate analysis (PCA), immunohistochemistry (caspase-3 and β-catenin), and a docking study were performed. Results indicated that three plant extracts significantly decreased epididymal sperm density and motility. Moreover, their effects on testicular cells were also assured by histopathological evaluations. Metabolomic profiling of the bioactive plant extracts showed the presence of diverse phytochemicals, mostly oleanane saponins, phenolic diterpenes, and lupane triterpenes. A docking study on caspase-3 enzyme showed that oleanane saponins possessed the highest binding affinity. An immunohistochemistry assay on β-catenin and caspase-3 indicated that Albizzia lebbeck was the most active extract for decreasing immunoexpression of β-catenin, while Rosmarinus officinalis showed the highest activity for increasing immunoexpression of caspase-3. The spermatogenesis decreasing the activity of A. lebbeck, Anagallis arvensis, and R. officinalis can be mediated via up-regulation of caspase-3 and down-regulation of β-catenin existing in testis cells.

中文翻译：

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通过比较代谢组学和对接研究预测睾丸Caspase-3和β-Catenin调节剂。

已经探索了许多途径来寻找有效，安全和负担得起的替代危险女性避孕药具。草药提取物及其次级代谢产物是解决这个日益严重的问题的一些有趣的研究领域。这项研究旨在调查十种不同植物提取物对睾丸生精的影响。使用多种技术评估了这些提取物的化学特征与其对雄性生殖系统的体内作用之间的相关性。对大鼠口服大约60％的LD50氢甲醇提取物，持续60天。除睾丸组织病理学外，还评估了精液参数，性器官重量和男性性激素的血清水平。此外，使用（LC-HRESIMS）的代谢组学分析，多变量分析（PCA），进行了免疫组织化学（caspase-3和β-catenin）的对接研究。结果表明，三种植物提取物显着降低了附睾的精子密度和活力。此外，组织病理学评估也确保了它们对睾丸细胞的作用。生物活性植物提取物的代谢组学分析表明存在多种植物化学物质，主要是齐墩果皂苷，酚二萜和三聚戊二烯。对caspase-3酶的对接研究表明，齐墩果皂苷具有最高的结合亲和力。对β-catenin和caspase-3的免疫组织化学分析表明，Albizzia lebbeck是降低β-catenin免疫表达最活跃的提取物，而迷迭香在增加caspase-3免疫表达方面表现出最高的活性。