Vishwakarma Riya, Koshy Abel John, Kalath Haritha, Ramakrishnan Krishnapriya, John Anish, Soman Sowmya, Raju Rajesh, Rehman Niyas, Revikumar Amjesh
Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University), Mangalore, India.
Department of Pharmaceutics, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangalore, India.
OMICS. 2025 Sep;29(9):442-457. doi: 10.1177/15578100251370567. Epub 2025 Aug 22.
Conventional pharmacological interventions for erectile dysfunction (ED) primarily rely on the phosphodiesterase-5 (PDE5) inhibitors such as sildenafil, tadalafil, vardenafil, and avanafil that have side effects despite their therapeutic effects. PDE5 is the primary cyclic guanosine monophosphate-degrading enzyme located in the smooth muscles of the corpus cavernosum in the penile tissue that helps in relieving erection. Natural products and phytochemicals are viable sources of molecular leads for drug discovery and development and, thus, offer prospects for innovation in ED treatment. This study reports the screening of phytochemicals from the plant with an eye to identify molecular candidates that inhibit PDE5. Natural products-based compounds that selectively target PDE5 are poised to be useful in clinical management of ED, and potentially with lesser side effects. The following top three phytochemicals identified from showed higher negative binding affinities for the PDE5 enzyme: diosgenin,dehydro (-11.1 kcal/mol), ruscogenin (-11.1 kcal/mol), and hecogenin (-10.3 kcal/mol) compared with the control drug sildenafil (-8.8 kcal/mol). Hydrogen bonds and Van der Waals interactions were the predominant forces influencing the interactions formed in the protein-ligand complexes. The ΔG binding free energies for these top three phytochemicals, diosgenin,dehydro, ruscogenin, and hecogenin, were -19.99 ± 5.99 kcal/mol, -9.05 ± 5.16 kcal/mol, and -14.11 ± 5.33 kcal/mol, respectively. Importantly, diosgenin,dehydro, a saponin obtained from , was identified as a particularly promising candidate for PDE5 inhibition by virtue of its higher negative binding affinity and, therefore, displaying a potential in drug discovery and development for ED. In addition, pharmacokinetic analysis and toxicity assessments support the prospects of these -derived phytochemicals for future and research for innovation in ED therapeutics.
勃起功能障碍（ED）的传统药物干预主要依赖于磷酸二酯酶-5（PDE5）抑制剂，如西地那非、他达拉非、伐地那非和阿伐那非，这些药物虽有治疗效果，但也有副作用。PDE5是位于阴茎海绵体平滑肌中的主要环磷酸鸟苷降解酶，有助于缓解勃起。天然产物和植物化学物质是药物发现和开发中分子先导物的可行来源，因此为ED治疗的创新提供了前景。本研究报告了对一种植物中植物化学物质的筛选，旨在识别抑制PDE5的分子候选物。基于天然产物的化合物选择性靶向PDE5，有望用于ED的临床管理，且可能副作用较小。从[植物名称未给出]中鉴定出的以下三种顶级植物化学物质对PDE5酶显示出更高的负结合亲和力：薯蓣皂苷元、去氢薯蓣皂苷元（-11.1千卡/摩尔）、鲁斯可皂苷元（-11.1千卡/摩尔）和海柯皂苷元（-10.3千卡/摩尔），而对照药物西地那非为（-8.8千卡/摩尔）。氢键和范德华相互作用是影响蛋白质-配体复合物中形成相互作用的主要力量。这三种顶级植物化学物质，薯蓣皂苷元、去氢薯蓣皂苷元 和鲁斯可皂苷元的结合自由能ΔG分别为-19.99±5.99千卡/摩尔、-9.05±5.16千卡/摩尔和-14.11±5.33千卡/摩尔。重要的是，从[植物名称未给出]中获得的一种皂苷——去氢薯蓣皂苷元，因其更高的负结合亲和力而被确定为PDE5抑制的特别有前景的候选物，因此在ED药物发现和开发中显示出潜力。此外，药代动力学分析和毒性评估支持了这些从[植物名称未给出]衍生的植物化学物质在未来ED治疗创新研究中的前景。
