Bioinformatics and integrated pharmacology network to identify the therapeutic targets and potential molecular mechanism of alpha‐lipoic acid on primary ovarian insufficiency

Abstract

Women experiencing primary ovarian insufficiency (POI) are more likely to experience infertility, and its incidence is increasing worldwide annually. Recently, the role of alpha‐lipoic acid (ALA) in the treatment of POI has been reported. However, details of the potential pharmacological targets and related molecular pathways of ALA remain unclear and need to be elucidated. Thus, this study aims to elucidate the potential therapeutic target and related molecular mechanism of ALA on POI. First, the potential targets of POI and ALA‐related targets were downloaded from online public databases. Subsequently, the overlapped target genes between POI and ALA were acquired, and gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) analysis, protein–protein interaction (PPI) networks were performed and constructed. Finally, molecular docking was performed to verify protein‐to‐protein effect. A total of 152 potential therapeutic targets were identified. The biological processes of the intersecting targets were mainly involved in the cellular response to peptides, response to xenobiotic stimuli, and response to peptide hormones. The highly enriched pathways were the cAMP, PI3K/AKT, estrogen, progesterone mediated oocyte maturation, and apoptosis signaling pathways. The top 10 hub targets for ALA in the treatment of POI were STAT3, STAT1, CASP3, MTOR, PTGS2, CASP8, HSP90AA1, PIK3CA, MAPK1, and ESR1. The binding between ALA and all top hub targets were verified using the molecular docking analysis. In summary, using the systematic integrated pharmacology network and bioinformatics analysis, this study illustrated that ALA participates in the treatment of POI via multiple targets and multiple pathways mechanisms.

Type III adenylyl cyclase is essential for follicular development in female mice and their reproductive lifespan

“…Targeting the cAMP signaling pathway has been shown to be an effective strategy for treating POF. 53 For instance, an elevated cAMP concentration in the cumulus-oocyte complex enhances intercellular communication and supplies metabolites for oocyte growth. 54 In addition, the cAMP/BDNF pathway has been proposed as a potential therapeutic target for treating POF and infertility.…”