Department of Traditional Chinese Medicine (TCM) Gynecology, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Zhejiang Chinese Medical University, Hangzhou, China.
Front Endocrinol (Lausanne). 2022 Feb 11;13:813772. doi: 10.3389/fendo.2022.813772. eCollection 2022.
Maternal oocyte aging is strongly contributing to age-related decline in female fertility. Coenzyme Q10 (CoQ10) exerts positive effects in improving aging-related deterioration of oocyte quality, but the exact mechanism is unclear.
To reveal the system-level mechanism of CoQ10's anti-aging effect on oocytes based on network pharmacology.
This study adopted a systems network pharmacology approach, including target identification, data integration, network and module construction, bioinformatics analysis, molecular docking, and molecular dynamics simulation.
A total of 27 potential therapeutic targets were screened out. Seven hub targets (PPARA, CAT, MAPK14, SQSTM1, HMOX1, GRB2, and GSR) were identified. Functional and pathway enrichment analysis indicated that these 27 putative targets exerted therapeutic effects on oocyte aging by regulating signaling pathways (e.g., PPAR, TNF, apoptosis, necroptosisn, prolactin, and MAPK signaling pathway), and are involved oxidation-reduction process, mitochondrion, enzyme binding, reactive oxygen species metabolic process, ATP binding, among others. In addition, five densely linked functional modules revealed the potential mechanisms of CoQ10 in improving aging-related deterioration of oocyte quality are closely related to antioxidant, mitochondrial function enhancement, autophagy, anti-apoptosis, and immune and endocrine system regulation. The molecular docking study reveals that seven hub targets have a good binding affinity towards CoQ10, and molecular dynamics simulation confirms the stability of the interaction between the hub targets and the CoQ10 ligand.
This network pharmacology study revealed the multiple mechanisms involved in the anti-aging effect of CoQ10 on oocytes. The molecular docking and molecular dynamics simulation provide evidence that CoQ10 may act on these hub targets to fight against oocytes aging.
母体卵母细胞衰老强烈导致女性生育能力随年龄增长而下降。辅酶 Q10（CoQ10）在改善与衰老相关的卵母细胞质量恶化方面具有积极作用，但确切机制尚不清楚。
基于网络药理学揭示 CoQ10 对卵母细胞抗衰老作用的系统水平机制。
本研究采用系统网络药理学方法，包括靶标鉴定、数据整合、网络和模块构建、生物信息学分析、分子对接和分子动力学模拟。
筛选出 27 个潜在治疗靶点。确定了 7 个枢纽靶点（PPARA、CAT、MAPK14、SQSTM1、HMOX1、GRB2 和 GSR）。功能和途径富集分析表明，这 27 个假定靶点通过调节信号通路（如 PPAR、TNF、细胞凋亡、坏死性凋亡、催乳素和 MAPK 信号通路）对卵母细胞衰老发挥治疗作用，并参与氧化还原过程、线粒体、酶结合、活性氧物质代谢过程、ATP 结合等。此外，五个紧密连接的功能模块揭示了 CoQ10 改善与衰老相关的卵母细胞质量恶化的潜在机制与抗氧化、增强线粒体功能、自噬、抗细胞凋亡以及免疫和内分泌系统调节密切相关。分子对接研究表明，七个枢纽靶点与 CoQ10 具有良好的结合亲和力，分子动力学模拟证实了枢纽靶点与 CoQ10 配体之间相互作用的稳定性。
本网络药理学研究揭示了 CoQ10 对卵母细胞抗衰老作用涉及的多种机制。分子对接和分子动力学模拟为 CoQ10 可能作用于这些枢纽靶点以对抗卵母细胞衰老提供了证据。
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