Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility

AbstractObjective To investigate the target and mechanism of action of Bushen Huoxue Recipe (BSHX) for the treatment of infertility in polycystic ovary syndrome (PCOS), to provide a basis for the development and clinical application of herbal compounds.Methods Prediction and validation of active ing...

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Main Authors: Hanxue Wu, Peijuan Wu, Ying Zhu, Junjie Li, Haiyan Chen, Hongqiu Zhu
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Gynecological Endocrinology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/09513590.2024.2325000
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author Hanxue Wu
Peijuan Wu
Ying Zhu
Junjie Li
Haiyan Chen
Hongqiu Zhu
author_facet Hanxue Wu
Peijuan Wu
Ying Zhu
Junjie Li
Haiyan Chen
Hongqiu Zhu
author_sort Hanxue Wu
collection DOAJ
description AbstractObjective To investigate the target and mechanism of action of Bushen Huoxue Recipe (BSHX) for the treatment of infertility in polycystic ovary syndrome (PCOS), to provide a basis for the development and clinical application of herbal compounds.Methods Prediction and validation of active ingredients and targets of BSHX for the treatment of PCOS by using network pharmacology-molecular docking technology. In an animal experiment, the rats were randomly divided into four groups (control group, model group, BSHX group, metformin group, n = 16 in each group), and letrozole combined with high-fat emulsion gavage was used to establish a PCOS rat model. Body weight, vaginal smears, and number of embryos were recorded for each group of rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of ovarian and endometrial tissues, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the serum inflammatory factor levels. Expression levels of transforming growth factor-β (TGF-β), transforming growth factor beta activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), Vimentin, and E-cadherin proteins were measured by western blot (WB).Results Ninety active pharmaceutical ingredients were obtained from BSHX, involving 201 protein targets, of which 160 were potential therapeutic targets. The active ingredients of BSHX exhibited lower binding energy with tumor necrosis factor-α (TNF-α), TGF-β, TAK1, and NF-κB protein receptors (< −5.0 kcal/mol). BSHX significantly reduced serum TNF-α levels in PCOS rats (p < .01), effectively regulated the estrous cycle, restored the pathological changes in the ovary and endometrium, improved the pregnancy rate, and increased the number of embryos. The results of WB suggested that BSHX can down-regulate protein expression levels of TGF-β and NF-κB in endometrial tissue (p < .05), promote the expression level of E-cadherin protein (p < .001), intervene in the endometrial epithelial-mesenchymal transition (EMT) process.Conclusions TGF-β, TAK1, NF-κB, and TNF-α are important targets of BSHX for treating infertility in PCOS. BSHX improves the inflammatory state of PCOS, intervenes in the endometrial EMT process through the TGF-β/NF-κB pathway, and restores endometrial pathological changes, further improving the pregnancy outcome in PCOS.
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spelling doaj.art-911b5f8dcde04d839e3c2c6bf083ff7b2024-03-13T15:42:12ZengTaylor & Francis GroupGynecological Endocrinology0951-35901473-07662024-12-0140110.1080/09513590.2024.2325000Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertilityHanxue Wu0Peijuan Wu1Ying Zhu2Junjie Li3Haiyan Chen4Hongqiu Zhu5Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaClinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaClinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaClinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaClinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaCollege of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaAbstractObjective To investigate the target and mechanism of action of Bushen Huoxue Recipe (BSHX) for the treatment of infertility in polycystic ovary syndrome (PCOS), to provide a basis for the development and clinical application of herbal compounds.Methods Prediction and validation of active ingredients and targets of BSHX for the treatment of PCOS by using network pharmacology-molecular docking technology. In an animal experiment, the rats were randomly divided into four groups (control group, model group, BSHX group, metformin group, n = 16 in each group), and letrozole combined with high-fat emulsion gavage was used to establish a PCOS rat model. Body weight, vaginal smears, and number of embryos were recorded for each group of rats. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of ovarian and endometrial tissues, and an enzyme-linked immunosorbent assay (ELISA) was used to detect the serum inflammatory factor levels. Expression levels of transforming growth factor-β (TGF-β), transforming growth factor beta activated kinase 1 (TAK1), nuclear factor kappa-B (NF-κB), Vimentin, and E-cadherin proteins were measured by western blot (WB).Results Ninety active pharmaceutical ingredients were obtained from BSHX, involving 201 protein targets, of which 160 were potential therapeutic targets. The active ingredients of BSHX exhibited lower binding energy with tumor necrosis factor-α (TNF-α), TGF-β, TAK1, and NF-κB protein receptors (< −5.0 kcal/mol). BSHX significantly reduced serum TNF-α levels in PCOS rats (p < .01), effectively regulated the estrous cycle, restored the pathological changes in the ovary and endometrium, improved the pregnancy rate, and increased the number of embryos. The results of WB suggested that BSHX can down-regulate protein expression levels of TGF-β and NF-κB in endometrial tissue (p < .05), promote the expression level of E-cadherin protein (p < .001), intervene in the endometrial epithelial-mesenchymal transition (EMT) process.Conclusions TGF-β, TAK1, NF-κB, and TNF-α are important targets of BSHX for treating infertility in PCOS. BSHX improves the inflammatory state of PCOS, intervenes in the endometrial EMT process through the TGF-β/NF-κB pathway, and restores endometrial pathological changes, further improving the pregnancy outcome in PCOS.https://www.tandfonline.com/doi/10.1080/09513590.2024.2325000Bushen Huoxue Recipeendometrial epithelial-mesenchymal transitionpolycystic ovary syndrometransforming growth factor-β/nuclear factor kappa-B pathway
spellingShingle Hanxue Wu
Peijuan Wu
Ying Zhu
Junjie Li
Haiyan Chen
Hongqiu Zhu
Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility
Gynecological Endocrinology
Bushen Huoxue Recipe
endometrial epithelial-mesenchymal transition
polycystic ovary syndrome
transforming growth factor-β/nuclear factor kappa-B pathway
title Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility
title_full Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility
title_fullStr Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility
title_full_unstemmed Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility
title_short Bushen Huoxue Recipe inhibits endometrial epithelial-mesenchymal transition through the transforming growth factor-β/nuclear factor kappa-B pathway to improve polycystic ovary syndrome-mediated infertility
title_sort bushen huoxue recipe inhibits endometrial epithelial mesenchymal transition through the transforming growth factor β nuclear factor kappa b pathway to improve polycystic ovary syndrome mediated infertility
topic Bushen Huoxue Recipe
endometrial epithelial-mesenchymal transition
polycystic ovary syndrome
transforming growth factor-β/nuclear factor kappa-B pathway
url https://www.tandfonline.com/doi/10.1080/09513590.2024.2325000
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