Potential and Mechanisms of Indigenous Indonesian Medicinal Plants in Treating Sexual Dysfunction: A Systematic Review and Pharmacological Network Overview

Abstract

The epidemiology of Erectile Dysfunction (ED) continues to exhibit an increasing trend annually. The use of synthetic drugs in treating ED often leads to undesirable side effects and has limited efficacy. In Indonesia, several indigenous plants have been empirically utilized for ED remediation. This study aims to identify the latest scientific evidence on the potential of native Indonesian medicinal plants for ED treatment and elucidate the underlying molecular mechanisms using a systematic review and Pharmacological Network approach. A systematic review search was conducted across three databases (PubMed, Scopus, and Springer) without limiting the publication years. Article screening was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. Determination of compound target genes was carried out using GeneCards, while disease target genes were analyzed using DisGeNET. Network topology was explored with Cytoscape 3.10, and the construction of Protein-Protein Interaction Networks was realized using STRING version 12.0. GO and KEGG analyses were subsequently conducted with SRplot. The systematic review results showed that 12 articles met the inclusion criteria. The pharmacology network study revealed that compounds within Eurycoma longifolia, namely stigmasterol, eurycomanone, and eurycomalactone, target 13 genes associated with ED, which include BCL2, AKT1, SOAT1, PCSK9, ACHE, BDNF-AS, TMX2-CTNND1, GSK3B, LINCO1672, TP53, H19, HIF1A, and IL1B. These target genes are linked to the biological mechanism of steroid hormone biosynthesis essential for testosterone hormone formation. Thus, Eurycoma longifolia exhibits strong potential to be developed as a phytopharmaceutical candidate promising for the treatment of sexual dysfunction.

Note:
Funding declaration: This research was funded by the research and community service institute of the University of Airlangga on the internal research program year 2022 number 251/UN3/2022.

Conflict of Interests: The authors declare that there are no conflicts of interest.

Keywords: Aphrodisiacs, Erectile Dysfunction, eurycomanone, stigmasterol, testosterone