The Treatment of Tubal Inflammatory Infertility using Yinjia Tablets through EGFR/MEK/ERK Signaling Pathway based on Network Pharmacology


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Аннотация

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.

Об авторах

Yefang Huang

, Hospital of Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Zhelin He

, Guang'an Traditional Chinese Medicine Hospital

Email: info@benthamscience.net

Hang Zhou

School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Yi Wen

, Hospital of Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Xiaoli Ji

, Hospital of Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Weijun Ding

School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Boyu Zhu

, Hospital of Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Yongqing Zhang

, Hospital of Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Ying Tan

, Hospital of Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Kun Yang

School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine

Email: info@benthamscience.net

Yan Wang

, Hospital of Chengdu University of Traditional Chinese Medicine

Автор, ответственный за переписку.
Email: info@benthamscience.net

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