Phytomedicine, Biochemical Toxicology and Biotechnology Research Laboratories, Department of Biochemistry, College of Sciences, Afe Babalola University, PMB 5454, Ado-Ekiti 360001, Nigeria.
Department of Biochemistry, Faculty of Biological Sciences, Alex Ekwueme Federal University Ndufu Alike Ikwo, P.O. Box 1010, Abakaliki 480101, Nigeria.
Int J Mol Sci. 2024 Nov 18;25(22):12362. doi: 10.3390/ijms252212362.
Erectile dysfunction (ED) is a multifactorial social problem affecting men worldwide. While phosphodiesterase type 5 inhibitors (PDE5) like sildenafil are commonly used, they often present side effects, underscoring the need for alternative therapies. Therefore, this study investigated the potential of phytochemicals from in the management of ED. A library of phytochemicals from was generated, prepared, and interacted with six key enzymes implicated in ED, including PDE5, using the Schrödinger Maestro suite. The results identified catechin, epicatechin, and gallic acid as the leading compounds with significant binding affinities for the targeted enzymes. Catechin and epicatechin (-9.877 and -11.408 kcal/mol, respectively) exhibited comparable binding affinities to sildenafil (-11.926 kcal/mol) on PDE5. The MD simulation results also revealed superior stability and ability to maintain interaction with key amino acids at the active site of PDE5 over the entire simulation period for these compounds. These compounds also demonstrated favorable ADMET profiles over sildenafil, including high gastrointestinal absorption and no violation of Lipinski's rule, indicating good bioavailability and drug likeness. These findings suggest that flavonoids from , especially catechin and epicatechin, have potential in the management of ED by interacting with multiple targets involved in its pathogenesis.
勃起功能障碍（ED）是一个全球性的多因素社会问题，影响着全世界的男性。虽然磷酸二酯酶 5 抑制剂（PDE5）如西地那非等被广泛应用，但它们常常会出现副作用，这凸显了寻找替代疗法的必要性。因此，本研究旨在探讨 中的植物化学物质在 ED 治疗中的潜力。从 中生成、制备了一个植物化学物质文库，并使用 Schrödinger Maestro 套件与 6 种与 ED 相关的关键酶（包括 PDE5）进行了相互作用。结果表明，儿茶素、表儿茶素和没食子酸是具有显著结合亲和力的主要化合物，针对这些目标酶。儿茶素和表儿茶素（分别为-9.877 和-11.408 kcal/mol）在 PDE5 上的结合亲和力与西地那非（-11.926 kcal/mol）相当。MD 模拟结果还表明，这些化合物在整个模拟过程中在 PDE5 的活性部位与关键氨基酸的相互作用更稳定，维持时间更长。这些化合物在 ADMET 特性方面也优于西地那非，包括高胃肠道吸收和不违反 Lipinski 规则，表明它们具有良好的生物利用度和类药性。这些发现表明，来自 的类黄酮，特别是儿茶素和表儿茶素，通过与参与其发病机制的多个靶点相互作用，具有治疗 ED 的潜力。
