Department of Traditional Chinese Medical Gynecology, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Endocrinol (Lausanne). 2021 Apr 19;12:630504. doi: 10.3389/fendo.2021.630504. eCollection 2021.
Diminished 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.
A systems pharmacology strategy was proposed to elucidate the potential therapeutic mechanism of melatonin on DOR at the molecular, pathway, and network levels.
The systems pharmacological approach consisted of target identification, data integration, network construction, bioinformatics analysis, and molecular docking.
From 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.
This 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.
卵巢储备功能降低（DOR）显著增加了女性不孕的风险，并导致生殖技术失败。最近，褪黑素改善卵巢储备（OR）的作用引起了广泛关注。然而，褪黑素改善 OR 的药理作用靶点和机制的细节尚不清楚。
提出了一种系统药理学策略，从分子、途径和网络水平阐明褪黑素治疗 DOR 的潜在治疗机制。
系统药理学方法包括靶标识别、数据整合、网络构建、生物信息学分析和分子对接。
从分子角度看，鉴定出 26 个潜在的治疗靶标。它们参与了与 DOR 发展相关的生物学过程，如生殖结构发育、上皮细胞增殖、外在凋亡信号通路、PI3K 信号通路等。鉴定出 8 个枢纽靶标（MAPK1、AKT1、EGFR、HRAS、SRC、ESR1、AR 和 ALB）。从途径水平看，鉴定出 17 个显著通路，包括 PI3K-Akt 信号通路和雌激素信号通路。此外，这 17 条信号通路与 26 个潜在的治疗靶标相互作用，形成 4 个功能模块。从网络角度看，通过调节五个靶标子网络（衰老、细胞生长和死亡、发育和再生、内分泌和免疫系统），褪黑素可以表现出抗衰老、抗凋亡、内分泌和免疫系统调节作用。分子对接结果表明，褪黑素与所有枢纽靶标结合良好。
本研究通过抗衰老、抗凋亡、内分泌和免疫系统调节作用，系统直观地说明了褪黑素改善 OR 的可能药理学机制。
