In vitro and in silico profiling of phenolics in Pentaclethra macrophylla leaf extract on key proteins linked to erectile dysfunction
DOI:
https://doi.org/10.2478/AMB-2024-0051Keywords:
African oil bean, HPLC-DAD, phytochemical screening, antioxidant assays, molecular docking, MD simulationAbstract
Introduction: Erectile dysfunction (ED) which is the inability to maintain an erection during sexual activity, is one of the most prevalent sexual dysfunctions, with mild to severe ED affecting an estimated 5-20% of men globally and about 322 million men may be affected globally by 2025. Aim: The present study was carried out to explore the phenolic constituents of Pentaclethra macrophylla, its antioxidant properties and potential binding mechanism on the key proteins linked to erectile dysfunction. Method: The method used included phytochemical screening, high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) quantification, in vitro analyses as well as in silico analyses such as target prediction, molecular docking and molecular dynamics (MD) simulation. Results: The phytochemical screening revealed that the extract contains various phytochemicals such as alkaloids, flavonoids, tannins, saponins and terpenoids. The total flavonoid and total phenolic contents were increased with increasing concentrations of the extract while DPPH and nitric oxide percentage scavenged activities were not significantly changed across the concentrations. The chromatogram of the phenolic contents of P. macrophyla obtained from HPLC-DAD indicated the presence of major compounds such as naringin, ellagic acid, epicatechin, epigallocatechin gallate, quercetin, myricetin, and rutin. The results of the target prediction showed that compounds relevant to ED are naringin, kaempferol, quercetin, and myricetin. Molecular docking results indicated that they have affinity for myeloperoxidase, followed by phosphodiesterase 5 (PDE5) and acetylcholinesterase. Naringin has the highest binding affinity (-11.040 kcal.mol-1) for myeloperoxidase, and 9.333 kcal.mol-1 for PDE5. The results of MDS indicate changes in the binding energy and stability of the complex of PDE5 with naringin as well as myeloperoxidase with naringin. Conclusion: Overall, the results proposed naringin as the potential bioactive compound in P. macrophylla that could be useful for treatment of erectile dysfunction.
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