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

Frontiers in Endocrinology

Qin Zhang¹  Yun Chen¹  Ying Zhao¹  Chenyun Miao¹  Liuqing Yang¹  Yu Xing²  Hongbin Xu³ 

[1] Department of Traditional Chinese Medical Gynecology, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, China;Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China;Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China;

关键词: diminished ovarian reserve (DOR);    ovarian reserve (OR);    melatonin;    potential therapeutic targets;    signaling pathways;    biological processes;   

DOI  :  10.3389/fendo.2021.630504

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown