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.
Highlights
In 2020, 1.03% of the women were suffering from adenomyosis (AM), and approximately 90% of them were accompanied by menorrhagia, progressive dysmenorrhea, pelvic pain, dysmenorrhea, and infertility [1]
Previous studies have found that Traditional Chinese medicine (TCM) treatment can alleviate dysmenorrhea, shorten the menstrual time, decrease menstrual volume, reduce uterine volume, and lower CA125 levels in AM patients [12,13,14]
Guizhi Fuling Wan (GZFLW) is one of the classic traditional Chinese herbal formulas widely used in the clinical treatment of AM [8], and studies have confirmed that the side effect of GZFLW on AM is only 1.99% [15]
Summary
In 2020, 1.03% of the women were suffering from adenomyosis (AM), and approximately 90% of them were accompanied by menorrhagia, progressive dysmenorrhea, pelvic pain, dysmenorrhea, and infertility [1]. Current therapeutic approaches, including operative treatment, nonsteroidal anti-inflammatory drugs, and endocrine therapy, have been used to suppress inflammation, relieve pain, and improve fertility. Erefore, it is of great clinical significance to develop alternative therapeutic strategies to improve the outcome of AM patients. Traditional Chinese medicine (TCM), which has been widely used in clinical practice in China for thousands of Evidence-Based Complementary and Alternative Medicine years, has made considerable contributions to the relief of AM [6]. Guizhi Fuling Wan (GZFLW) is an effective Chinese medicinal formula for AM which is used in TCM [7, 8]. Us, the “multicomponent and multitarget” therapeutic mechanism of GZFLW in treating AM is still obscure, hindering its clinical use. For a comprehensive understanding of the mechanism of action of GZFLW, a novel analysis method is needed [9]
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