Integrated serum metabolomics and network pharmacology reveal molecular mechanism of Qixue Huazheng formula on peritoneal fibrosis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 23, 2025

Background Peritoneal 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 treat PD-related peritoneum injury related; however, the active components, core genes, underlying mechanism involved remain unclear. Methods The anti-PF effects of QXHZF were verified in vivo vitro . Targets QXHZF-mediated improvement PD-induced PF predicted using network pharmacology analysis. Metabolites associated with treatment analyzed by serum metabolomics. Integration metabolomics findings identified potentially important pathways, metabolites, targets, molecular docking studies confirmed interactions key components targets. Western blotting (WB), quantitative real-time PCR (qRT-PCR), TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, flow cytometry conducted. Results had potent therapeutic efficacy against according WB, qRT-PCR, pathological section examination. Network pharmacological analysis indicated that multiple compounds contributed improving modulating various targets pathways. Differential metabolites Integrated data steroid hormone biosynthesis, Ras signaling pathway, apoptosis, estrogen QXHZF. Metabolite-target analyses revealed can bind receptor 1 (ESR1) rapidly accelerated fibrosarcoma (RAF1) through its components. WB demonstrated reversed activation above-mentioned thereby inhibiting PD fluid-induced PF. Conclusion significantly ameliorate may regulate signaling, apoptosis this context.

Language: Английский

ELABELA promotes the migration and homing of bone marrow mesenchymal stem cells to myocardial injury sites through the ERK1/2/miR-299a-5p/Exo70 pathway

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 3, 2025

Background Bone marrow mesenchymal stem cells (BMSCs) hold promise for repairing myocardial injury following acute infarction (AMI), but their clinical application is hindered by poor migration, homing efficiency, and survival rates. Previously, we demonstrated that ELABELA (ELA), a small peptide, enhances the of rat BMSCs under hypoxia-reoxygenation (H/R) conditions activating ERK1/2. However, role ELA in promoting migration to injured cardiomyocytes remains unclear. Methods Primary neonatal ventricular myocytes (NRVMs) were isolated cultured. NRVMs exposed H/R mimic microenvironment AMI vitro. The toward myocardium was assessed different treatment groups using transwell chemotaxis assays. Additionally, vivo studies performed infarction/reperfusion (MI/RI) model with DIR-labeled BMSCs. Cardiac repair evaluated through fluorescence imaging, echocardiography, histological analysis. Transcriptome sequencing bioinformatics analysis employed identify validate mechanisms which promoted A dual luciferase assay used investigate interaction between Exo70 miR-299a-5p. Subsequently, series experimental procedures performed, including sequential silencing APJ or Exo70, overexpression miR-299a-5p, inhibition ERK1/2 phosphorylation, assessment scratch assays, detection F-actin polymerization via immunofluorescence, evaluation expression levels each factor qPCR Western blotting. Results In vitro, ability ELA-pretreated significantly augmented environment. pretreatment effectively heightened capacity site proficiency damage vivo. revealed upregulation pretreated BMSCs, migration. Overexpression miR-299a-5p reduced impaired also activated while ERK1/2·with U0126 abrogated increasing reducing Exo70. Conclusion receptor, downregulating upregulating providing potential therapeutic strategy improving cell-based cardiac repair.

Language: Английский