Abstract
We aimed to investigate therapeutic effect of Bushenhuoxue recipe in intrauterine adhesions (IUA) and explore the underlying molecular mechanism via integrating network pharmacology and in vitro experimental verification. The active compounds and gene targets of Bushenhuoxue recipe were screened in the TCMSP database and the IUA-related genes were identified using GeneCards database by the keyword “Intrauterine adhesions”. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to reveal the underlying molecular mechanism of Bushenhuoxue recipe treating IUA. T-HESC cells were inducted to fibrotic state using TGF-β1 of 10 ng/ml concentration treating for 24 h. RT-qPCR or western blot was used to demonstrate the expression levels of fibrosis markers (COL1A1 and α-SMA) and KEGG pathway markers. Cell counting kit-8 (CCK8) assay was performed to illustrate the cell viability of endometrial stromal cell. The treatment of Bushenhuoxue recipe could significantly inhibit the proliferation and fibrosis of endometrial stromal cells. We obtained a total of 169 no-repeat ingredients of Bushenhuoxue recipe and 3044 corresponding targets. After taking intersection with 4230 no-repeat IUA-related genes, a total of 83 target genes related to both Bushenhuoxue recipe and IUA were finally identified. KEGG analysis found that PI3K-AKT signaling pathway might be the key pathway. Further experiment revealed that PI3K-AKT signaling pathway was significantly activated in endometrial stromal cells of fibrotic state and the treatment of Bushenhuoxue recipe could inhibit the PI3K-AKT signaling pathway. Further rescue assay demonstrated that Bushenhuoxue recipe suppressed the proliferation and fibrosis of endometrial stromal cells via PI3K-AKT signaling pathway. Bushenhuoxue recipe suppresses the proliferation and fibrosis of endometrial stromal cells via PI3K-AKT signaling pathway, eventually inhibiting the progression of IUA.
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The data used in the current study are available from the corresponding author on reasonable request.
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Funding
This study is supported by Natural Science Fundation of Fujian Province (No. 2021J01903), Project of Fujian Provincial Clinical Research Center For Gynecological Minimally Invasive and Holistic Integrative Pelvic Floor Medicine (No. X202201-Clinical Center), and Young and Middle-aged Key Personnel Training Project of Fujian Provincial Health Commission (No. 2020GGB037).
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Lingli Wang and Lingzi Zhuang wrote the original draft. Xiaohong Wang and Zhejing Hong reviewed edited the original draft. Lingli Wang contributed to the methodology. Yajing Lu did the investigation. Jin Jia contributed to the formal analysis. Cailing Chen curated the data. Ying Zhang and Lingli Wang contributed to the conceptualization and the visualization. Xiaohong Wang supervised the project. Xiaohong Wang and Xiaohong Wang administrated the project.
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Wang, L., Zhuang, L., Lu, Y. et al. Integrating Network Pharmacology and In Vitro Experimental Verification Revealing Bushenhuoxue Recipe Against Intrauterine Adhesions via PI3K-AKT Signaling Pathway. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10732-6
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DOI: https://doi.org/10.1007/s10528-024-10732-6