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.
References
Cai FF et al (2019) Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic analysis. Biomed Pharmacother 114:108863
Emingr M et al (2023) Prevention of intrauterine adhesions. Ceska Gynekol 88(3):210–213
Guo Z et al (2022) β-Klotho promotes the development of intrauterine adhesions via the PI3K/AKT signaling pathway. Int J Mol Sci 23(19):11294
Han J et al (2022) Using network pharmacology to explore the mechanism of Panax notoginseng in the treatment of myocardial fibrosis. J Diabetes Res 2022:8895950
Healy MW et al (2016) Intrauterine adhesion prevention after hysteroscopy: a systematic review and meta-analysis. Am J Obstet Gynecol 215(3):267-275.e7
Jiashuo WU et al (2022) Integration strategy of network pharmacology in Traditional Chinese Medicine: a narrative review. J Tradit Chin Med 42(3):479–486
Johary J et al (2014) Efficacy of estrogen therapy in patients with intrauterine adhesions: systematic review. J Minim Invasive Gynecol 21(1):44–54
Kou L et al (2020) Therapeutic options and drug delivery strategies for the prevention of intrauterine adhesions. J Control Release 318:25–37
Lee WL et al (2021) Focus on the primary prevention of intrauterine adhesions: current concept and vision. Int J Mol Sci 22(10):5175
Lu JR et al (2018) Mechanism research of Bu-Shen-Huo-Xue formula against renal fibrosis in rats with 5/6 nephrectomy via E-cadherin, α-SMA, and TGF-β1. Clin Nephrol 90(1):53–58
Lv H et al (2021) Hydrogel, a novel therapeutic and delivery strategy, in the treatment of intrauterine adhesions. J Mater Chem B 9(33):6536–6552
Ma J et al (2021) Recent trends in therapeutic strategies for repairing endometrial tissue in intrauterine adhesion. Biomater Res 25(1):40
Nogales C et al (2022) Network pharmacology: curing causal mechanisms instead of treating symptoms. Trends Pharmacol Sci 43(2):136–150
Song YT et al (2021) Stem cell-based therapy for ameliorating intrauterine adhesion and endometrium injury. Stem Cell Res Ther 12(1):556
Sroussi J et al (2022) Does hyaluronic acid gel reduce intrauterine adhesions after dilation and curettage in women with miscarriage? A multicentric randomized controlled trial (HYFACO Study). Am J Obstet Gynecol 227(4):597.e1-597.e8
Sun L et al (2019) Establishment and comparison of different intrauterine adhesion modelling procedures in rats. Reprod Fertil Dev 31(8):1360–1368
Wang T et al (2022) Based on network pharmacology and in vitro experiments to prove the effective inhibition of myocardial fibrosis by Buyang Huanwu decoction. Bioengineered 13(5):13767–13783
Yang X et al (2022) BushenHuoxue recipe for the treatment of prethrombotic state of ACA-positive recurrent miscarriage via the regulation of the PI3K-AKT signaling pathway. Evid Based Complement Alternat Med 2022:2385534
Yu J et al (2018) Interaction between BMSCs and EPCs promotes IUA angiogenesis via modulating PI3K/Akt/Cox2 axis. Am J Transl Res 10(12):4280–4289
Zhang SS et al (2017) Three-dimensional structure micelles of heparin-poloxamer improve the therapeutic effect of 17β-estradiol on endometrial regeneration for intrauterine adhesions in a rat model. Int J Nanomedicine 12:5643–5657
Zhang R et al (2019) Network pharmacology databases for traditional Chinese medicine: review and assessment. Front Pharmacol 10:123
Zhang H et al (2021) Bioinformatics and network pharmacology identify the therapeutic role and potential mechanism of melatonin in AD and rosacea. Front Immunol 12:756550
Zhang W et al (2022) Potential molecular mechanism of Guishen Huoxue decoction against intrauterine adhesion based on network pharmacology. Evid Based Complement Alternat Med 2022:4049147
Zhang S et al (2023) MenSCs transplantation improve the viability of injured endometrial cells through activating PI3K/Akt pathway. Reprod Sci 30:3325
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