Muritala Hamdalat Folake, Abdulrahman Ridwan Ayinla, Oyewusi Habeebat Adekilekun, Muhammad Hashim Ndaman
Department of Biochemistry, University of Ilorin, Ilorin, Nigeria.
Biochemistry unit, Department of Science Technology, The Federal Polytechnic, P.M.B 5351, Ado Ekiti, Ekiti State, Nigeria.
Cell Biochem Biophys. 2025 Mar 13. doi: 10.1007/s12013-025-01713-6.
Erectile dysfunction in men may result as a side effect of the use of serotonin reuptake inhibitors such as paroxetine. Enzymes like phosphodiesterase 5 (PDE-5) and arginase are promising therapeutic targets for managing erectile dysfunction while creatinine kinase-myocardial band (CK-MB) serves as a marker for coronary artery disease. To manage these conditions, it is necessary to seek options in medicinal herbs. Rauwolfia vomitoria (RV) is a plant that has been used as an aphrodisiac but the inhibitory mechanism against these enzymes remain unclear. The study used in-vivo enzymatic biomarkers and molecular docking approach to better understand their inhibitory mechanism. Forty-eight adult male Wistar rats were divided into six groups of eight rats: naive control, paroxetine (PXT, 10 mg/kg), PXT+sildenafil citrate (4 mg/kg), PXT + RVE (12.5, 25 and 50 mg/kg). Exposure to PXT lasted for twenty-one days, and treatment with sildenafil citrate and RVE took place for the next seven days. On day twenty-nine, the rats were sacrificed under anaesthesia and various biochemical assays (PDE-5, Arginase, nitric oxide (NO) were carried out on penile tissue homogenate while CK-MB, lipid profile and testosterone were assayed in the serum of rats. This study also employed gas chromatography -flame ionization detection (GC-FID) to identify the phytoconstituents in RV. From our findings, PXT significantly increased PDE-5, Arginase activities with a concomitant decrease in NO concentration. Rauwolfia vomitoria extract (RVE) decreased the activities of the penile PDE 5 and arginase activities, and increased NO concentrations in dose-dependent ways (12.5, 25, and 50 mg/kg body weight). RVE showed an increase in testosterone and a decrease in CK-MB activities. Moreover, the result of lipid profile revealed the significant reversal of the changes caused by PXT administration, indicating the potential of the extract in ameliorating paroxetine-induced dyslipidemia. All of the phytochemicals found by GC-FID docked against PDE-5 had the lowest binding energies ( - 9.4 to -7.0 kcal/mol) when likened to that of sildenafil citrate ( - 7.4 kcal/mol). The phytochemicals were also docked against arginase which released the lowest binding energy between -10.5 and -9.0 kcal/mol when compared with sildenafil citrate ( - 9.4 kcal/mol). This study is relevant in the design of new treatment option for ED and coronary artery disease.
男性勃起功能障碍可能是使用5-羟色胺再摄取抑制剂（如帕罗西汀）的副作用。磷酸二酯酶5（PDE-5）和精氨酸酶等酶是治疗勃起功能障碍的有前景的治疗靶点，而肌酸激酶同工酶（CK-MB）是冠状动脉疾病的标志物。为了治疗这些疾病，有必要在草药中寻找选择。催吐萝芙木（RV）是一种被用作壮阳药的植物，但其对这些酶的抑制机制尚不清楚。该研究使用体内酶生物标志物和分子对接方法来更好地了解其抑制机制。48只成年雄性Wistar大鼠被分为6组，每组8只：空白对照组、帕罗西汀组（PXT，10mg/kg）、PXT+枸橼酸西地那非组（4mg/kg）、PXT+催吐萝芙木提取物低剂量组（12.5mg/kg）、PXT+催吐萝芙木提取物中剂量组（25mg/kg）、PXT+催吐萝芙木提取物高剂量组（50mg/kg）。暴露于PXT持续21天，随后7天用枸橼酸西地那非和催吐萝芙木提取物进行治疗。在第29天，大鼠在麻醉下处死，对阴茎组织匀浆进行各种生化检测（PDE-5、精氨酸酶、一氧化氮（NO）），同时对大鼠血清进行CK-MB、血脂谱和睾酮检测。本研究还采用气相色谱-火焰离子化检测（GC-FID）来鉴定催吐萝芙木中的植物成分。根据我们的研究结果，PXT显著增加了PDE-5、精氨酸酶的活性，同时NO浓度降低。催吐萝芙木提取物（RVE）以剂量依赖的方式（12.5、25和50mg/kg体重）降低了阴茎PDE 5和精氨酸酶的活性，并增加了NO浓度。RVE显示睾酮增加，CK-MB活性降低。此外，血脂谱结果显示，PXT给药引起的变化得到了显著逆转，表明该提取物在改善帕罗西汀引起的血脂异常方面具有潜力。与枸橼酸西地那非（-7.4kcal/mol）相比，GC-FID发现的所有与PDE-5对接的植物化学物质具有最低的结合能（-9.4至-7.0kcal/mol）。这些植物化学物质也与精氨酸酶对接，与枸橼酸西地那非（-9.4kcal/mol）相比，其释放的最低结合能在-10.5至-9.0kcal/mol之间。这项研究对于设计勃起功能障碍和冠状动脉疾病的新治疗方案具有重要意义。
