Therapeutic targets of L-carnitine against polycystic ovary syndrome and the underlying signaling mechanisms

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of child-bearing age. Accumulating evidence has shown the benefits of L-carnitine for the treatment of PCOS. However, little is known about the targets of L-carnitine against PCOS and the underlying mechanisms. In the present study, we performed used analysis of network pharmacology with using bioinformatics tools to identify targets, biological functions, and the signaling pathways of L-carnitine's action in PCOS treatment. In addition, we performed quantitative reverse transcription-polymerase chain reaction to verify the expression of the target genes in human ovarian granulosa tumor cells. We identified 91 primary causal targets of L-carnitine in PCOS treatment from the data and 6 optimal core targets of L-carnitine. These core targets included phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1), hypoxia-inducible factor 1-alpha (HIF-1A), Toll-like receptor 4 (TLR-4), proto-oncogene tyrosine-protein kinase Src (SRC), histone acetyltransferase p300 (EP300), and mitogen-activated protein kinase 1 (MAPK1). In addition, we identified the top 10 items in the biological processes, biological function, cellular component, and molecular function and signaling pathways (including top 30 items) potentially involved in the action of L-carnitine against PCOS. The hub genes potentially involved in the action of L-carnitine against PCOS and interlaced networks from the Kyoto Encyclopedia of Genes and Genomes Mapper assay were determined. Finally, the expression of PIK3R1, HIF-1A, TLR-4, and MAPK1 in human ovarian granulosa tumor cells was validated using quantitative reverse transcription-polymerase chain reaction, and the results were consistent with those of our integrated analysis. The action of L-carnitine against PCOS was mechanistically and pharmacologically implicated with major biological pathways, such as the HIF-1A, PI3K-Akt, and other signaling pathways. These primary predictive biotargets might be used to manage PCOS in the clinical setting after further development.