Title:The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets
through EGFR/MEK/ERK Signaling Pathway based on Network
Pharmacology
Volume: 25
Issue: 4
Author(s): Yefang Huang, Zhelin He, Hang Zhou, Yi Wen, Xiaoli Ji, Weijun Ding, Boyu Zhu, Yongqing Zhang, Ying Tan, Kun Yang and Yan Wang*
Affiliation:
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
Keywords:
Yin jia tablet, tubal inflammation, network pharmacology, EGFR signaling pathway, ESR1, STRING database.
Abstract:
Background: Salpingitis obstructive infertility (SOI) refers to infertility caused by abnormal
conditions such as tubal adhesion and blockage caused by acute and chronic salpingitis.
SOI has a serious impact on women's physical and mental health and family harmony, and it is a
clinical problem that needs to be solved urgently.
Objective: The purpose of the present study was to explore the potential pharmacological mechanisms
of the Yinjia tablets (Yin Jia Pian, YJP) on tubal inflammation.
Methods: Networks of YJP-associated targets and tubal inflammation-related genes were constructed
through the STRING database. Potential targets and pathway enrichment analysis related
to the therapeutic efficacy of YJP were identified using Cytoscape and Database for Annotation,
Visualization, and Integrated Discovery (metascape). E. coli was used to establish a rat model of
tubal inflammation and to validate the predictions of network pharmacology and the therapeutic
efficacy of YJP. H&E staining was used to observe the pathological changes in fallopian tubes.
TEM observation of the ultrastructure of the fallopian tubes. ELISA was used to detect the changes
of IL-6 and TNF-α in fallopian tubes. Immunohistochemistry was used to detect the expression of
ESR1. The changes of Bcl-2, ERK1/2, p-ERK1/2, MEK, p-MEK, EGFR, and p-EGFR were detected
by western blot.
Results: Through database analysis, it was found that YJP shared 105 identical targets with the
disease. Network pharmacology analysis showed that IL-6, TNF, and EGFR belong to the top 5
core proteins associated with salpingitis, and EGFR/MEK/ERK may be the main pathway involved.
The E. coli-induced disease rat model of fallopian tube tissue showed damage, mitochondrial
disruption, and increased levels of the inflammatory factors IL-6 and TNF-α. Tubal inflammatory
infertility rats have increased expression of Bcl-2, p-ERK1/2, p-MEK, and p-EGFR, and
decreased expression of ESR1. In vivo, experiments showed that YJP improved damage of tissue,
inhibited shedding of tubal cilia, and suppressed the inflammatory response of the body. Furthermore,
YJP inhibited EGFR/MEK/ERK signaling, inhibited the apoptotic protein Bcl-2, and upregulated
ESR1.
Conclusion: This study revealed that YJP Reducing tubal inflammation and promoting tissue repair
may be associated with inhibition of the EGFR/MEK/ERK signaling pathway.
