Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis
BackgroundPeritoneal fibrosis (PF) causes peritoneal dialysis (PD) withdrawal due to ultrafiltration failure. Qixue Huazheng formula (QXHZF), comprising Astragalus membranaceus, Centella asiatica, and Ligusticum sinense, is applied to treat PD-related peritoneum injury related; however, the active c...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1515038/full |
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| author | Xiaohui Meng Xiaohui Meng Li Sheng Yongqing You Yongqing You Huibo Dai Manshu Yu Funing Wang Funing Wang Ziren Zhou Ziren Zhou Yun Shan Meixiao Sheng |
| author_facet | Xiaohui Meng Xiaohui Meng Li Sheng Yongqing You Yongqing You Huibo Dai Manshu Yu Funing Wang Funing Wang Ziren Zhou Ziren Zhou Yun Shan Meixiao Sheng |
| author_sort | Xiaohui Meng |
| collection | DOAJ |
| description | BackgroundPeritoneal fibrosis (PF) causes peritoneal dialysis (PD) withdrawal due to ultrafiltration failure. Qixue Huazheng formula (QXHZF), comprising Astragalus membranaceus, Centella asiatica, and Ligusticum sinense, is applied to treat PD-related peritoneum injury related; however, the active components, core genes, and underlying mechanism involved remain unclear.MethodsThe anti-PF effects of QXHZF were verified in vivo and in vitro. Targets underlying QXHZF-mediated improvement of PD-induced PF were predicted using network pharmacology analysis. Metabolites associated with QXHZF treatment of PD-related PF were analyzed by serum metabolomics. Integration of network pharmacology and serum metabolomics findings identified potentially important pathways, metabolites, and targets, and molecular docking studies confirmed the interactions of key components and targets. Western blotting (WB), quantitative real-time PCR (qRT-PCR), TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and flow cytometry were conducted.ResultsQXHZF had potent therapeutic efficacy against PF according to WB, qRT-PCR, and pathological section examination. Network pharmacological analysis indicated that multiple QXHZF compounds contributed to improving PF by modulating various targets and pathways. Differential metabolites were identified by serum metabolomics analysis. Integrated data analysis indicated that steroid hormone biosynthesis, the Ras signaling pathway, apoptosis, and estrogen signaling contributed to the effects of QXHZF. Metabolite-target network and molecular docking analyses revealed that QXHZF can bind to estrogen receptor 1 (ESR1) and rapidly accelerated fibrosarcoma 1 (RAF1) through its components. WB demonstrated that QXHZF treatment reversed activation of the above-mentioned signaling pathways, thereby inhibiting PD fluid-induced PF.ConclusionQXHZF can significantly ameliorate PD-induced PF and may regulate estrogen signaling, the Ras pathway, and apoptosis in this context. |
| format | Article |
| id | doaj-art-226c67d769de44abbd6116254aa5cfd2 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-226c67d769de44abbd6116254aa5cfd22025-01-23T06:56:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011610.3389/fphar.2025.15150381515038Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosisXiaohui Meng0Xiaohui Meng1Li Sheng2Yongqing You3Yongqing You4Huibo Dai5Manshu Yu6Funing Wang7Funing Wang8Ziren Zhou9Ziren Zhou10Yun Shan11Meixiao Sheng12Department of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaMedical Research Center of First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nephrology, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan, ChinaDepartment of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaMedical Research Center of First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaMedical Research Center of First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaMedical Research Center of First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaDepartment of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, ChinaBackgroundPeritoneal fibrosis (PF) causes peritoneal dialysis (PD) withdrawal due to ultrafiltration failure. Qixue Huazheng formula (QXHZF), comprising Astragalus membranaceus, Centella asiatica, and Ligusticum sinense, is applied to treat PD-related peritoneum injury related; however, the active components, core genes, and underlying mechanism involved remain unclear.MethodsThe anti-PF effects of QXHZF were verified in vivo and in vitro. Targets underlying QXHZF-mediated improvement of PD-induced PF were predicted using network pharmacology analysis. Metabolites associated with QXHZF treatment of PD-related PF were analyzed by serum metabolomics. Integration of network pharmacology and serum metabolomics findings identified potentially important pathways, metabolites, and targets, and molecular docking studies confirmed the interactions of key components and targets. Western blotting (WB), quantitative real-time PCR (qRT-PCR), TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and flow cytometry were conducted.ResultsQXHZF had potent therapeutic efficacy against PF according to WB, qRT-PCR, and pathological section examination. Network pharmacological analysis indicated that multiple QXHZF compounds contributed to improving PF by modulating various targets and pathways. Differential metabolites were identified by serum metabolomics analysis. Integrated data analysis indicated that steroid hormone biosynthesis, the Ras signaling pathway, apoptosis, and estrogen signaling contributed to the effects of QXHZF. Metabolite-target network and molecular docking analyses revealed that QXHZF can bind to estrogen receptor 1 (ESR1) and rapidly accelerated fibrosarcoma 1 (RAF1) through its components. WB demonstrated that QXHZF treatment reversed activation of the above-mentioned signaling pathways, thereby inhibiting PD fluid-induced PF.ConclusionQXHZF can significantly ameliorate PD-induced PF and may regulate estrogen signaling, the Ras pathway, and apoptosis in this context.https://www.frontiersin.org/articles/10.3389/fphar.2025.1515038/fulltraditional Chinese medicineQixue Huazheng formulaperitoneal fibrosismetabolomicsnetwork pharmacologyestrogen signaling |
| spellingShingle | Xiaohui Meng Xiaohui Meng Li Sheng Yongqing You Yongqing You Huibo Dai Manshu Yu Funing Wang Funing Wang Ziren Zhou Ziren Zhou Yun Shan Meixiao Sheng Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis Frontiers in Pharmacology traditional Chinese medicine Qixue Huazheng formula peritoneal fibrosis metabolomics network pharmacology estrogen signaling |
| title | Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis |
| title_full | Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis |
| title_fullStr | Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis |
| title_full_unstemmed | Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis |
| title_short | Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis |
| title_sort | integrated serum metabolomics and network pharmacology reveal molecular mechanism of qixue huazheng formula on peritoneal fibrosis |
| topic | traditional Chinese medicine Qixue Huazheng formula peritoneal fibrosis metabolomics network pharmacology estrogen signaling |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1515038/full |
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