Physicochemical assessment and insilico studies on the interaction of 5-HT2c receptor with herbal medication bioactive compounds used in the treatment of premature ejaculation

Abstract

Abstract Premature ejaculation (PE) affects one in every four men around the world, and there is no known cure for this sexual dysfunction. Many non-herbal and herbal medications are prescribed for their treatment, some of which have not been thoroughly evaluated for their efficacy and role in the body. Premature ejaculation herbal treatment medication produced in Abia State, Nigeria, were analysed for its efficacy using Fluoxetine as a compared compound, a selective serotonin reuptake inhibitor in the treatment of PE. The herbal drugs were analysed using both classical and spectroscopic methods for the determination of its proximate content, phytochemical analysis, heavy metals concentrations and bioactive compounds. The interactions with the 5-HT2c serotonin receptors were investigated using in silico computational analysis, molecular docking, and pharmacokinetic properties of the selected compounds with ADMET screening. The availability of important phytochemicals such as alkaloids, terpenoids, flavonoids, tannins, and saponins was recorded, and the proximate content values were within the recommended ranges. Heavy metals such as Pb (46 mg/kg), Cd (22 mg/kg), Ni (35 mg/kg), and Mn (132 mg/kg) were found in excess of the recommended limits. Fifty-one compounds were discovered in the herbal drug samples, which were then screened for drug-ability using the Lipinski rule. In this study, six (6) compounds with the highest binding affinities among the compounds under investigation were reported. All six compounds were found to have binding affinity scores ranging from −7.5 kcal/mol to −10.5 kcal/mol. Their interactions in the active sites of the target receptors were with amino acids residues like ASP 134, VAL 135, SER 138, VAL 208, PHE 327, VAL 354, TRY 358, PHE 328, GLY 218, ASN 331, ALA 222, and LEU 350 sharing hydrophobic and electrostatic bonds. The study predicted the ADMET properties of the compounds under investigation and discovered that some of them had good pharmacokinetic properties and CYP2C19 enzyme inhibitory potential. This research suggests that these compounds could be active ingredients in herbal medications used to treat premature ejaculation. However, after using this medication, serum concentrations of patients can be measured to further assess its efficacy.