Mechanisms of a Patented Chinese Herbal Medicine for Treating Hypothyroidism in In Vitro Fertilization-Embryo Transfer: A Combination of Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Background: Qu's formula 6 (QUF6), a patented Chinese herbal medicine, is used to treat hypothyroidism in the context of in vitro fertilization-embryo transfer (IVF-ET). This research aims to identify the potential bioactive components and elucidate the underlying molecular mechanisms by which QUF6 cures hypothyroidism during IVF-ET.

Material and methods: To find the active components of QUF6, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and relevant literature were searched. GeneCards and other resources were used to find the targets associated with hypothyroidism and IVF-ET. Using Cytoscape software, the network of interactions was created between the targets and components, the proteinprotein interaction (PPI) network was built, and significant targets were verified. Afterward, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on crucial targets. Finally, molecular docking and dynamic modeling were carried out to analyze the essential components and core targets of QUF6.

Results: By creating an interaction network, it was discovered that 92 active components in QUF6 can operate on 25 disease-related targets, with quercetin and other components playing important pharmacodynamic roles. Tumor necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1B (IL-1B), apoptosis regulator Bcl-2 (BCL2), prostaglandin G/H synthase 2 (PTGS2), cellular tumor antigen p53 (TP53), and epidermal growth factor (EGF) were the main targets for the therapy of hypothyroidism. The KEGG pathway enrichment study identified 91 signaling pathways, whereas the GO enrichment analysis identified 1608 entries. Through molecular docking and MD simulations, stable binding was identified between the top five active constituents and the top seven potential targets.

Conclusion: Quercetin, beta-sitosterol, kaempferol, 7-ketocholesterol, and rehmapicrogenin were determined to be the active ingredients in QUF6. The potential mechanism of action for QUF6 may involve modulation of TNF, IL6, IL1B, BCL2, PTSG2, TP53, and EGF to regulate oxidative stress levels, inflammation responses, and apoptosis processes associated with hypothyroidism during IVF-ET.