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Biological mechanism of Danggui Powder in improving endometrial vascular dysplasia induced by clomiphene citrate
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DOI   10.11656/j.issn.1672-1519.2024.02.15
Key Words   Danggui Powder;clomiphene citrate;vascular endothelial growth factor(VEGF);angiogenin;endometrial angiogenesis;network pharmacology
Author NameAffiliationE-mail
ZHANG Chuxin Beijing University of Chinese Medicine, Beijing 100029, China  
CHENG Yuli Beijing University of Chinese Medicine, Beijing 100029, China  
HU Honglin Department of Traditional Chinese Medicine, Hangzhou Shulan Hospital, Hangzhou 310015, China  
HU Ruiyao Beijing University of Chinese Medicine, Beijing 100029, China  
GAO Lin Beijing University of Chinese Medicine, Beijing 100029, China gaolin93@aliyun.com 
Abstract
    [Objective] To study the effect of Danggui Powder and its disassembled prescriptions on dysplasia endometrial vascular caused by clomiphene citrate,based on network pharmacology and experimental verification. [Methods] TCMSP and SwissTargetPredicition databases were used to obtain the active components and potential drug targets of Danggui Powder. GeneCards and OMIM databases were used to search the targets of dysplasia endometrial vascular caused by clomiphene citrate. The intersection of drugs and dysplasia endometrial vascular related targets was selected. The network of “Chinese medicine-core component-target” and the protein-protein interactions(PPI) network were conducted. The enrichment analysis of GO and KEGG were carried out. On the first day after estrus,the model group and each treatment group were given clomiphene suspension for 5 consecutive days. Meanwhile,the treatment groups were given aspirin,Danggui Powder,Chuanxiong-Danggui-Shaoyao,Huangqin-Baizhu solution for 8 consecutive days. The rat endometrial microvessel density,the expression of vascular endothelial growth factor VEGFA,FLT1,KDR,Ang1,Ang2 and Tie2 were determined by Immunohistochemistry. [Results] A total of 24 potential targets of Danggui Powder were obtained by network pharmacology,such as VEGFA,EGFR,FGF2,KDR,SRC,FLT1,etc. A total of 1524 items of biological processes,36 items of cellular components and 94 items of molecular functions were involved in the enrichment analysis of GO. And 118 pathways were involved in the enrichment analysis of KEGG,such as PI3K-Akt signaling pathway,Rap1 signaling pathway,Relaxin signaling pathway,etc. Compared with the normal group,the rat endometrial microvessel density,VEGFA,FLT1,KDR,Ang1,Ang2 and Tie2 in the model group significantly decreased(P<0.01). Compared with the model group,the rat endometrial microvessel density,KDR,FLT1,Ang1,Ang2 and Tie2 in each treatment group increased(P<0.05 or P<0.01). In addition to the Huangqin-Baizhu group,VEGFA in the other treatment groups significantly increased(P<0.01). [Conclusion] Danggui Powder and its disassembled prescription can reduce the damage of clomiphene citrate for endometrial to varying degrees,restore the expression of VEGFA,FLT1,KDR,Ang1,Ang2 and Tie2,and improve the endometrial receptivity.

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