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

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.

Therapeutic Effect of Abelmoschus manihot on Type 2 Diabetic Nonproliferative Retinopathy and the Involvement of VEGF.

OBJECTIVE: To evaluate the efficacy of Abelmoschus manihot in treating type 2 diabetic nonproliferative retinopathy. METHODS: It was a randomized controlled clinical trial. The recruited eighty subjects with type 2 diabetic nonproliferative retinopathy were randomly divided into treatment group and control group. The two groups received basic treatments including control of blood glucose, blood pressure and blood lipid, management of diet, exercise and health education, and monitoring of relevant indicators. Additionally, the treatment group was given oral administration of Abelmoschus manihot. All subjects were followed up on monthly basis for consecutive six months. The related parameters including diabetic retinopathy (DR) incidence rates, "Early Treatment Diabetic Retinopathy Study" (ETDRS) vision scores, retinal thicknesses in macular region, serum vascular endothelial growth factor (VEGF) levels, and biochemical indicators of both groups before and after treatment were accurately collected and statistically analyzed. RESULTS: There were no significant differences of DR severity levels, ETDRS vision scores, macular retinal thicknesses such as cube average thickness (CAT), central subfield thickness (CST), and cube volume (CV), and serum VEGF levels between two groups before treatment. Meanwhile, there were no significant differences of demographic characteristics, case terminations, blood glucose, blood lipid, blood pressure, biochemical indicators of hepatorenal function, hypoglycemic drugs, hypotensive drugs, and other basic treatments between two groups during six months treatment. The present study suggested that the remission rate of DR and the ETDRS vision score in the treatment group were significantly higher than those of the control group (remission rate: 25.4% vs 9.3%, P=0.01; ETDRS score: 78 (72, 82) vs 72 (67, 80), P=0.0002) while the progression rate of DR in the treatment group was significantly lower than that of the control group (progression rate: 4.2% vs 18.7%, P=0.007) after six months treatment. In addition, the CAT, CST, CV, and serum VEGF levels of the treatment group were significantly improved after the treatment (CAT: 286 (278, 302) vs 282 (270, 295) µm, P < 0.0001; CST: 251 (239, 274) vs 248 (235, 265) µm, P < 0.0001; CV: 10.3 (10.0, 10.9) vs 10.1 (9.7, 10.6) mm3, P < 0.0001; VEGF: 0.21 (0.14, 0.58) vs 0.16 (0.10, 0.23) ng/ml, P=0.0026), while there were no significant differences of the control group before and after treatment (CAT: 287 (279, 294) vs 287 (279, 295) µm, P=0.27; CST: 250 (240, 266) vs 252 (238, 266) µm, P=0.72; CV: 10.4 (10.1, 10.6) vs 10.4 (10.1, 10.7) mm3, P=0.53; VEGF: 0.21 (0.13, 0.66) vs 0.23 (0.12, 0.64) ng/ml, P=0.85). CONCLUSION: The study offered the novel evidence for the therapeutic effect of Abelmoschus manihot on type 2 diabetic nonproliferative retinopathy, which was associated with improved VEGF. This trial is registered with ChiCTR1800019292.