Network Pharmacology Approach for Predicting Targets of Zishen Yutai Pills on Premature Ovarian Insufficiency

Abstract

Background and Purpose. Premature ovarian insufficiency (POI) is a serious reproductive disease in females that is characterized by menstrual and ovulation disorders and infertility. The clinical efficacy of complementary and alternative medicine (CAM) has been reported in POI, including compound Chinese medicine. Zishen Yutai Pills (ZSYTP), a well-known patented Chinese medicine, has been widely used for treating POI; however, the pharmacological mechanism and molecular targets of ZSYTP remain unknown. Here, we systematically elucidated the pharmacological mechanism of ZSYTP on POI using a network pharmacology approach and further validated our findings with molecular docking. Methods. A comprehensive strategy based on several Chinese herb databases and chemical compound databases was established to screen active compounds of ZSYTP and predict target genes. For network pharmacological analysis, network construction and gene enrichment analysis were conducted and further verified by molecular docking. Results. A total of 476 target genes of ZSYTP were obtained from 205 active compounds. 13 herbs of ZSYTP overlapped on 8 active compounds based on the compound-target-disease network (C-T network). 20 biological processes and 9 pathways were strongly connected to the targets of ZSYTP in treating POI, including negative regulation of gene expression, mRNA metabolic process, hypoxia-inducible factor 1 (HIF-1) signaling pathway, and gluconeogenesis. Finally, molecular docking was visualized. Conclusion. Intriguingly, the signal pathways and biological processes uncovered in this study implicate inflamm-aging and glucose metabolism as potential pathological mechanisms of POI. The therapeutic effect of ZSYTP could be mediated by regulating glucose metabolism and HIF-1 signal pathway. Collectively, this study sheds light on the therapeutic potential of ZSYTP on POI.

Network analysis and experimental approach to investigate the potential therapeutic mechanism of zishen yutai pills on premature ovarian insufficiency

“…6 A. According to previous studies, the binding strength of a protein is negatively related to its energy; < −1.2 kcal/mol and < −5.0 kcal/mol can be accredited as practical and dynamite docking, respectively [ 36 ]. In terms of potential targets, HRAS and TP53 possessed the best binding outcomes.…”

“…In this study, we predicted potential targets of ZSYTP against POI using a network pharmacology approach. Although previous studies have performed network pharmacology analysis and concluded that ZSYTP could be ameliorating POI via glucose metabolism and the HIF-1 signaling pathway, these results were not supported by sufficient experimental validation [ 36 ]. In addition, the use of different pharmacological network analysis methods and databases would inevitably lead to different conclusions.…”

Curcumin and its nano-formulations: Defining triple-negative breast cancer targets through network pharmacology, molecular docking, and experimental verification

“…The binding energy was used to score the binding affinity of ligand and receptor. It is generally acknowledged that binding energy<0 kcal/mol indicates the interaction of ligand and receptor is spontaneous, and binding energy < -5 kcal/mol means that the ligand and receptor may assemble ( Feng et al, 2021 ; Ni et al, 2021 ; Li et al, 2022a ; Li et al, 2022b ). The docking scores of CUR or the co-crystallized ligand with the selected protein targets (receptors) were shown in Table 2 .…”

Investigation of the Mechanism of Zishen Yutai Pills on Polycystic Ovary Syndrome: A Network Pharmacology and Molecular Docking Approach

“…Our team conducted a network pharmacology study on the effect of ZSYTP on POI. One hypothesis put forward by our previous study was that ZSYTP upregulates the hypoxia-inducible factor-1 (HIF1) signaling pathway [ 32 ], thereby encouraging oocyte competence through a multitude of pathways. Similarly, the KEGG analysis of ZSYTP on PCOS highlighted the HIF-1 pathway, indicating a possible relationship between the treatment efficacy of ZSYTP and this pathway.…”