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

Abstract

BackgroundMaternal 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.ObjectiveTo reveal the system-level mechanism of CoQ10’s anti-aging effect on oocytes based on network pharmacology.MethodsThis study adopted a systems network pharmacology approach, including target identification, data integration, network and module construction, bioinformatics analysis, molecular docking, and molecular dynamics simulation.ResultA 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.ConclusionThis 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.

Network pharmacology and experiment indicated that medicinal food homologous components play important roles in insomnia

“…The confidence level was set to 0.4, and free targets were hidden. The resulting TSV format file was downloaded and imported into Cytoscape 3.8.2 (Yang, Liu, et al., 2022) for topological analysis. The PPI network contained 210 nodes and 3411 edges, with an average node degree of 32.5 and an average local clustering coefficient of 0.56.…”

“…We utilized Cytoscape 3.8.2 (Yang, Liu, et al., 2022) to construct a network diagram that visualized the relationship between the components of medicinal and food homologous substances, the core targets associated with insomnia, and the relevant signaling pathways. Using the degree values of the active ingredients, we ranked and sorted them to identify the top five active ingredients.…”

“…Insulin receptor (IR) is a tetramer composed of two alpha subunits located outside the cell (INS‐specific binding site) and two beta subunits located inside the cell (important sites for signal transduction) (Sacco et al., 2012). The activation of insulin receptor substrate (IRS) (Kané et al., 2020) can recruit and activate a variety of signaling proteins, mediating the multiple‐vector cell signaling effect of IRS (Yang, Wang, et al., 2022). Extracellular regulated protein kinase (ERK) (Guo et al., 2020) is the main member of the mitogen‐activated protein kinase family, which mainly regulates apoptosis, proliferation, and differentiation (Karisch et al., 2011).…”

Simiao Wan and its ingredients alleviate type 2 diabetes mellitus via IRS1/AKT2/FOXO1/GLUT2 signaling

“…In addition, network pharmacology can predict the bioactive ingredients and mechanisms of TCM for the treatment of diseases. Many studies have demonstrated the scientific nature of network pharmacology ( 9 , 10 ). Network pharmacology provides a new research paradigm for evidence-based medicine systems and will accelerate our understanding of TCM.…”

Análise do perfil transcriptômico e da morfologia ovariana de Scaptotrigona bipunctata (Lepeletier) e as estratégias reprodutivas das abelhas eussociais

“…Em roedores, foi verificado que CoQ10 neutraliza o envelhecimento da fisiología ovariana. Em humanos, o declínio da concentraçao de CoQ10 em alguns tecidos após os 30 anos e pensado coincidir com o declínio da fertilidade e aumento das aneuplodias embrionarias (Rosen et al, 1995;Crane, 2001;Morre et al, 2003;Miles et al, 2004;Hargreaves, 2003: Ben-Meir et al, 2015: Barcelos 8€ Haas, 2019: Yang et al, 2022. Em A. mellifera, foi verificado que operarias tratadas com CoQ10 vivem mais e possuem maior proteçao contra Nosema, alem disso, foi observado maior atividade de enzimas com funçao antioxidante (CAT, GST, SOD) nas abelhas tratadas (Strachecka et al, 2014).…”