Ameliorative Effect of Rauwolfia vomitoria Ethanol Extract on the Erectile Dysfunction Complicated with Coronary Artery Disease: An In-Vivo and Molecular Docking Approach

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Abstract
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.

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