Gunasekaran Prasanth, Velmurugan Yogaswaran, Arputharaj David Stephen, Savaridasson Jose Kavitha, Hemamalini Madhukar, Venkatachalam Rajakannan
Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, Tamil Nadu, India.
Department of Physics, PSG College of Arts and Science, Coimbatore, Tamil Nadu, India.
Front Chem. 2023 Jan 26;11:1096177. doi: 10.3389/fchem.2023.1096177. eCollection 2023.
Bioactive molecules from natural sources having contraceptive properties were excellent alternatives for modern hormonal contraceptives. Researchers around the world were working on identifying contraceptive leads targeting the male reproductive system rather than the usual female contraceptives. The lack of proper understanding on male contraceptive protein drug targets leads to insufficient evidence on activities of identified contraceptive compounds. The proteins specific to the male reproductive system and involved in sperm-egg fusion will be an excellent drug target to identify the male non-hormonal, reversible contraceptive leads. Inhibiting sperm hyaluronidase activity by natural non-hormonal compounds will lead to reversible and non-hormonal male contraception. The Aegle marmelos Linn. is one such important medicinal plant with valuable phytocompounds, used traditionally as a potential contraceptive measure. The in vivo experiments on leaf extracts of Aegle marmelos. Linn containing terpenes, sterols, and alkaloids shows prominent contraceptive activities. Moreover, this study explores the potential ability of the leaf extract on inhibiting the sperm hyaluronidase action with additional molecular details on the interaction between sperm hyaluronidases and three phytocompounds such as aegeline, marmin, and marminol. The in vitro hyaluronidase inhibition assay and Computer Assisted Sperm Analysis (CASA) were used to evaluate the male contraceptive properties of the Aegle marmelos Linn. leaf extract. To identify the interaction profile of aegeline, marmin, and marmenol on sperm cell hyaluronidases the in-silico methods such as molecular docking, Non-Covalent Interaction analysis, Molecular dynamics, and Molecular Mechanics Poisson Boltzmann Surface Area were used. The results of in vitro hyaluronidase inhibition assay and Computer Assisted Sperm Analysis shows the inhibition of hyaluronidase enzymatic activity and reduced sperm activities in the presence of leaf extracts. After incubation with leaf extracts for about 30 minutes time intervals show, the motility drops from progressive to non-progressive and ended up with complete immotile in 100 μg/ml concentration of leaf extract. The results of molecular docking, Non-Covalent Interaction analysis, Molecular dynamics, and Molecular mechanics Poisson Boltzmann Surface Area show that the phytocompounds marmin, and aegeline have the potential ability to inhibit sperm hyaluronidase.
具有避孕特性的天然来源生物活性分子是现代激素避孕药的绝佳替代品。世界各地的研究人员致力于确定针对男性生殖系统而非传统女性避孕药的避孕先导物。对男性避孕蛋白药物靶点缺乏正确认识，导致已鉴定的避孕化合物活性证据不足。男性生殖系统特有的、参与精卵融合的蛋白质将是识别男性非激素、可逆避孕先导物的绝佳药物靶点。天然非激素化合物抑制精子透明质酸酶活性将导致可逆的非激素男性避孕。印度枳椇就是这样一种重要的药用植物，含有有价值的植物化合物，传统上用作一种潜在的避孕措施。对含有萜类、甾醇和生物碱的印度枳椇叶提取物进行的体内实验显示出显著的避孕活性。此外，本研究探讨了叶提取物抑制精子透明质酸酶作用的潜在能力，并提供了精子透明质酸酶与三种植物化合物（如印度黄皮碱、羟基马钱苷和羟基马钱醇）之间相互作用的更多分子细节。体外透明质酸酶抑制试验和计算机辅助精子分析（CASA）用于评估印度枳椇叶提取物的男性避孕特性。为了确定印度黄皮碱、羟基马钱苷和羟基马钱醇对精子细胞透明质酸酶的相互作用谱，使用了分子对接、非共价相互作用分析、分子动力学和分子力学泊松玻尔兹曼表面积等计算机模拟方法。体外透明质酸酶抑制试验和计算机辅助精子分析结果表明，在叶提取物存在下，透明质酸酶的酶活性受到抑制，精子活性降低。在与叶提取物孵育约30分钟的时间间隔后显示，在100μg/ml浓度的叶提取物中，精子活力从进行性下降到非进行性，最终完全失去活力。分子对接、非共价相互作用分析、分子动力学和分子力学泊松玻尔兹曼表面积的结果表明，植物化合物羟基马钱苷和印度黄皮碱具有抑制精子透明质酸酶的潜在能力。
