A network pharmacology approach to explore active compounds and pharmacological mechanisms of a patented Chinese herbal medicine in the treatment of endometriosis

Abstract

Objective Endometriosis is a common benign disease in women of reproductive age. Qu’s formula (QUF) is a patented Chinese herbal medicine for treating endometriosis that has been proven to be effective in treating and preventing the recurrence of endometriosis. This study is aimed to discover its molecular mechanism and to explore the potential drug targets. Methods A QUF target and endometriosis-related gene set was identified by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases and five disease-gene databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, and a protein–protein interaction (PPI) network was established to discover the potential mechanism. MalaCards was searched for targets and signaling pathways related to endometriosis, and the search results were also used to identify the key factors in QUF. Molecular docking was performed to visualize the interactions between the effective molecules and proteins encoded by critical genes. Cell experiments and molecular dynamics (MD) simulations were used to further validate the therapeutic effects of the active compounds in QUF on endometriosis. Results A compound-target network with 117 nodes (94 genes and 23 active compounds) and 224 edges was generated. The results of GO and KEGG analyses indicated that QUF could act by regulating the immune response, apoptosis and proliferation, oxidative stress, and angiogenesis. VEGFA, CXCL8, CCL2, IL1B and PTGS2 were selected for molecular docking analysis from two critical subnetworks with high correlation scores in MalaCards, and the active compounds of QUF had binding potential and high affinity for them. The mRNA expression levels of CCL2, IL1B and PTGS2 significantly decreased after treatment with quercetin. MD simulations showed that the combinations of quercetin and these proteins were relatively stable. Conclusion The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism by which QUF protects against endometriosis. Our findings not only confirm the clinical effectiveness of QUF but also provide a foundation for further experimental study.

Computational Systems Pharmacology and Molecular Docking Reveal an Anti-Apoptosis and Anti-Inflammatory Mechanism of Compound Angelica Ligusticum Wallichii Granules in the Treatment of Endometriosis

“…At present, many studies have shown that TCM has a synergistic effect on the treatment of endometriosis. 26,27 The mechanisms involved include regulating the immune response, apoptosis, and angiogenesis, 28 which are consistent with our findings. However, many studies use Chinese herbal medicine directly, and the quality control may be unstable.…”

Bu-Shen-Tian-Jing formulas alleviate the mitochondrial damage induced by oxidative stress in ovarian granulosa cells exposed to DEHP through the HDAC3-HSP90AA pathway

“…To determine the optimal binding location of the active compounds and protein macromolecules, molecular docking was performed as previously described (Wu et al. 2022 ). Genes from the networks with the highest degree were selected for molecular docking analysis.…”

UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol’s Metabolic Target in Endometriosis

“…Third, there are huge medical costs [ 14 , 15 ]. However, Traditional Chinese Medicine (TCM) can be effective in avoiding these disadvantages to some extent [ 16 , 17 ].…”