Melatonin: Multi-Target Mechanism Against Diminished Ovarian Reserve Based on Network Pharmacology

Abstract

BackgroundDiminished ovarian reserve (DOR) significantly increases the risk of female infertility and contributes to reproductive technology failure. Recently, the role of melatonin in improving ovarian reserve (OR) has attracted widespread attention. However, details on the pharmacological targets and mechanisms of melatonin-improved OR remain unclear.ObjectiveA systems pharmacology strategy was proposed to elucidate the potential therapeutic mechanism of melatonin on DOR at the molecular, pathway, and network levels.MethodsThe systems pharmacological approach consisted of target identification, data integration, network construction, bioinformatics analysis, and molecular docking.ResultsFrom the molecular perspective, 26 potential therapeutic targets were identified. They participate in biological processes related to DOR development, such as reproductive structure development, epithelial cell proliferation, extrinsic apoptotic signaling pathway, PI3K signaling, among others. Eight hub targets (MAPK1, AKT1, EGFR, HRAS, SRC, ESR1, AR, and ALB) were identified. From the pathway level, 17 significant pathways, including the PI3K-Akt signaling pathway and the estrogen signaling pathway, were identified. In addition, the 17 signaling pathways interacted with the 26 potential therapeutic targets to form 4 functional modules. From the network point of view, by regulating five target subnetworks (aging, cell growth and death, development and regeneration, endocrine and immune systems), melatonin could exhibit anti-aging, anti-apoptosis, endocrine, and immune system regulation effects. The molecular docking results showed that melatonin bound well to all hub targets.ConclusionThis study systematically and intuitively illustrated the possible pharmacological mechanisms of OR improvement by melatonin through anti-aging, anti-apoptosis, endocrine, and immune system regulation effects.

Towards Personalized Antioxidant Use in Female Infertility: Need for More Molecular and Clinical Studies

“…The concentration of melatonin in the follicular fluid was shown to be positively correlated with antral follicle count, oocyte quality, and IVF outcomes [ 45 , 46 ]. A recent study, based on network pharmacology, demonstrated a multi-target mechanism of action of melatonin against DOR [ 47 ].…”

Therapeutic Target Analysis and Molecular Mechanism of Melatonin - Treated Leptin Resistance Induced Obesity: A Systematic Study of Network Pharmacology

“…The predicted PPI network was visualized by Cytoscape (v3.9.0) and using Maximal Clique Centrality (MCC) topological analysis, the foremost 10 core genes were recognized by Cytoscape plugin CytoHubba (39). For network construction, we used Cytoscape software (1) melatonin with its targets, (2) LR with Obesity and its PPI interaction, (3) PPI interaction of common targets of melatonin and LR with Obesity, (4) functional modules of top 10 network using clustermaker2 Glay (Community Cluster) algorithm, and (5) subnetworks of therapeutic targets enriched in different pathway classes (19).…”

“…Melatonin is an effective antioxidant and possesses free radical scavenging and antiinflammatory activities. A bioinformatic study by Yang et al explained the possible pharmacological mechanisms in treating diminished ovarian reserve by melatonin (19). Melatonin activates antioxidant enzymes at the mRNA level and increases anti-inflammatory activity and immune function (20).…”

Systematic Understanding of Anti-Aging Effect of Coenzyme Q10 on Oocyte Through a Network Pharmacology Approach

“…Currently, although anti-oocyte aging activities exerted by CoQ10 have been reported, details of biomarkers and the biological pathways through which CoQ10 counteracts oocyte aging are limited. In previous studies, a network pharmacologybased approach was successfully used to reveal all candidate targets, functions, and potential therapeutic mechanisms of drugs (20)(21)(22). In the present study, system network pharmacology combined with molecular docking was performed to reveal the potential targets and therapeutic mechanisms of CoQ10 against oocyte aging.…”