Utilizing network pharmacology and molecular docking to explore the underlying mechanism of Guizhi Fuling Wan in treating endometriosis

Abstract

Background Guizhi Fuling Wan (GZFLW) is a widely used classical Chinese herbal formulae prescribed for the treatment of endometriosis (EMs). This study aimed to predict the key targets and mechanisms of GZFLW in the treatment of EMs by network pharmacology and molecular docking. Methods Firstly, related compounds and targets of GZFLW were identified through the TCMSP, BATMAN-TCM and CASC database. Then, the EMs target database was built by GeneCards. The overlapping targets between GZFLW and EMs were screened out, and then data of the PPI network was obtained by the STRING Database to analyze the interrelationship of these targets. Furthermore, a topological analysis was performed to screen the hub targets. After that, molecular docking technology was used to confirm the binding degree of the main active compounds and hub targets. Finally, the DAVID database and Metascape database were used for GO and KEGG enrichment analysis. Results A total of 89 GZFLW compounds and 284 targets were collected. One hundred one matching targets were picked out as the correlative targets of GZFLW in treating EMs. Among these, 25 significant hub targets were recognized by the PPI network. Coincidently, molecular docking simulation indicated that the hub targets had a good bonding activity with most active compounds (69.71%). Furthermore, 116 items, including the inflammatory reaction, RNA polymerase, DNA transcription, growth factor activity, and steroid-binding, were selected by GO enrichment analysis. Moreover, the KEGG enrichment analysis results included 100 pathways focused on the AGE-RAGE pathway, HIF pathway, PI3K Akt pathway, MAPK pathway, and TP53 pathway, which exposed the potential mechanisms of GZFLW in treating EMs. Also, the MTT colorimetric assay indicated that the cell proliferation could be inhibited by GZFLW. Compared with the control group, the protein levels of P53, BAX, and caspase3 in the drug groups were all increased in Western blotting results. The results of flow cytometry showed that the percentage of apoptotic cells in the GZFLW group was significantly higher than that in the control group. Conclusion Through the exploration of network pharmacology and molecular docking technology, GZFLW has a therapeutic effect on EMs through multi-target mechanism. This study provided a good foundation for further experimental research.

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

“…When compared with GZFLW [ 8 ], we found many similar active compounds in QUF and GZFLW. The main compounds in QUF, such as quercetin, kaempferol, baicalein, beta-sitosterol, stigmasterol, ellagic acid, hederagenin, and (+)-catechin, were also included in GZFLW.…”

“…The pathways of QUF in treating endometriosis might be associated with the immune response, apoptosis and proliferation, oxidative stress, and angiogenesis. The AGE−RAGE signaling pathway in diabetic complications and the HIF−1 signaling pathway were also discovered in GZFLW and thought to be important in oxidative stress and angiogenesis [ 8 , 18 , 19 ]. MicroRNAs in cancer, one of the three pathways closely related to endometriosis in MalaCards, were also discovered in our study.…”

“…Guizhi Fuling Wan (GZFLW) is a classical prescription for endometriosis treatment in TCM [ 7 ]. A recent network pharmacology analysis indicated that GZFLW can treat endometriosis through multiple mechanisms [ 8 ]. Animal experiments have shown that GZFLW can attenuate endometriosis in rats by immunological regulation and induction of apoptosis [ 9 , 10 ].…”

Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal the Protective Effect of Salvianolic Acid C in a Rat Model of Ischemic Stroke

“…The binding energies between target proteins and SAC were in the range of −7.18 -−2.09 kcal/mol. According to the screening conditions for docking results (He et al, 2020;Wang et al, 2021), only nine target proteins had binding energy less than -5 kcal/mol with SAC (Table 3). Eventually, compared with the important targets enriched by KEGG pathway, four targets (KDR, IGF1, PPARG, and MMP1) were selected and displayed in a 3D graph (Figure 7).…”

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

“…Thus, the “multicomponent and multitarget” therapeutic mechanism of GZFLW in treating AM is still obscure, hindering its clinical use. Hence, for a comprehensive understanding of the mechanism of action of GZFLW, a novel analysis method is needed [ 9 ].…”