Integrating Network Pharmacology and Experimental Validation Deciphers the Mechanism of Guizhi Fuling Wan against Adenomyosis

Abstract

Aim. This study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification. Methods. The related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis. Results. A total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells’ estrogen resistance via GPER/EGFR signaling pathway. Conclusion. The endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.

Exploring the Mechanism of Yiqi Qingre Ziyin Method in Regulating Neuropeptide Expression for the Treatment of Atrophic Rhinitis

“…Codonopsis pilosula (20 g) was added to the prescription when patients presented with significant "qi" deficiency syndrome. In previous research, ingredients and targets of these herbs were downloaded from the traditional Chinese medicine systems pharmacology database [14][15][16][17]. An ingredient was defined as active when a combination of the following conditions was true: OB > 30% and DL > 0:18.…”

Analysis of the Mechanism of GuizhiFuling Wan in Treating Adenomyosis Based on Network Pharmacology Combined with Molecular Docking and Experimental Verification

“…Modern pharmacological studies showed that GFW could reduce the expression of vascular endothelial growth factor (VEGF), interleukin-2 (IL-2), and interleukin-8 (IL-8) in serum [ 11 ] and was found to be effective in rat models of AM [ 12 , 13 ]. Wang verified that GFW played a role in treating AM by regulating the estrogen signaling pathway [ 14 ]. Our group also performed some research on GFW in treating AM.…”