Akinjiyan Moses Orimoloye, Elekofehinti Olusola Olalekan, Oluwatuyi Adedotun Olayemi, Nwanna Esther Emem, Lawal Akeem Olalekan
Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology, Akure, Ondo State, Nigeria.
Teady Bioscience Research Laboratory, Akure, Ondo State, Nigeria.
Cell Biochem Biophys. 2025 Mar;83(1):555-572. doi: 10.1007/s12013-024-01486-4. Epub 2024 Aug 31.
Cissus populnea (CP) is a plant reported to possess an erection-enhancing ability, though mechanisms remain unclear. Drugs targeting phosphodiesterase 5 (PDE5) inhibition, such as sildenafil, have been employed to treat erectile dysfunction (EDRF), but they are associated with several complications. This study investigated the effect of C. populnea extracts (aqueous and saponin-rich) on the activity and gene expressions of proteins related to erection. PDE5, Nitric oxide synthase (NOS) and androgen receptor (AR) genes were studied using RT-PCR on CP-treated paroxetine-induced ERDF-rats. It also employed Schrödinger suites for investigations such as molecular and induced-fit docking, MMGBSA, ADMET, and QSAR profiling of CP-phytocompounds. C. populnea extracts reduce the activity and downregulate the expression of the PDE5 gene while upregulating the expressions of AR and NOS genes in the ERDF-rats relative to the control group. Five (leading) compounds with induced-fit docking (IFD) scores in kcal/mol, namely, stigmasterol (-638.73), daucosterol (-644.73), furostanol (-639.29), papaverine (-639.03), and capsaicin (-642.88), had better docking scores of -9.936, -9.824, -9.064, -8.863, and -8.736 kcal/mol, respectively, compared with those of sildenafil (-8.611 kcal/mol). They also showed an excellent ADMET profile, satisfying Lipinski's rule of five. The MMGBSA predictions revealed that stigmasterol, daucosterol, papaverine, and capsaicin had binding free energies of -45.29, -59.14, -50.63, and -50.47 kcal/mol, respectively, suggesting that they are significant inhibitors of PDE5. The QSAR model revealed that lead compounds possess good pIC50 values. These results indicate that C. populnea is a more promising possible treatment for controlling EDRF and deserves further research.
柔毛白粉藤（CP）是一种据报道具有增强勃起能力的植物，但其作用机制尚不清楚。靶向磷酸二酯酶5（PDE5）抑制的药物，如西地那非，已被用于治疗勃起功能障碍（EDRF），但它们存在一些并发症。本研究调查了柔毛白粉藤提取物（水提取物和富含皂苷的提取物）对与勃起相关蛋白质的活性和基因表达的影响。在经CP处理的帕罗西汀诱导的EDRF大鼠中，使用逆转录聚合酶链反应（RT-PCR）研究了PDE5、一氧化氮合酶（NOS）和雄激素受体（AR）基因。研究还使用薛定谔软件包对柔毛白粉藤植物化合物进行了分子对接、诱导契合对接、MMGBSA、ADMET和QSAR分析等研究。与对照组相比，柔毛白粉藤提取物降低了EDRF大鼠中PDE5基因的活性并下调其表达，同时上调了AR和NOS基因的表达。五种（主要）具有诱导契合对接（IFD）得分（千卡/摩尔）的化合物，即豆甾醇（-638.73）、胡萝卜苷（-644.73）、呋甾醇（-639.29）、罂粟碱（-639.03）和辣椒素（-642.88），与西地那非（-8.611千卡/摩尔）相比，分别具有更好的对接得分-9.936、-9.824、-9.064、-8.863和-8.736千卡/摩尔。它们还显示出优异的ADMET特性，符合Lipinski的五规则。MMGBSA预测显示，豆甾醇、胡萝卜苷、罂粟碱和辣椒素的结合自由能分别为-45.29、-59.14、-50.63和-50.47千卡/摩尔，表明它们是PDE5的有效抑制剂。QSAR模型显示主要化合物具有良好的半数抑制浓度负对数（pIC50）值。这些结果表明，柔毛白粉藤是控制EDRF更有前景的可能治疗方法，值得进一步研究。
