Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
10.13422/j.cnki.syfjx.20251167
- VernacularTitle:保心颗粒调控铁死亡治疗心力衰竭的潜在活性成分及分子机制分析
- Author:
Yu CHEN
1
;
Maolin WANG
2
;
Yun WANG
1
;
Yifan ZHAO
1
;
Jing XU
1
;
Hongwei WU
1
;
Fang WANG
3
;
Xiaoang ZHAO
1
;
Youming LI
4
;
Jixiang TIAN
1
Author Information
1. State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs， Institute of Chinese Materia Medica，China Academy of Chinese Medical Sciences，Beijing 100700，China
2. Jiangxi Province Key Laboratory of Traditional Chinese Medicine（TCM） Pharmacology， Institute of TCM Health Industry，China Academy of Chinese Medical Sciences，Nanchang 330115，China
3. Center for Food Evaluation，State Administration for Market Regulation，Beijing 100088，China
4. Jiangxi University of Chinese Medicine，Nanchang 330004，China
- Publication Type:Journal Article
- Keywords:
Baoxin granules;
heart failure;
ferroptosis;
ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）;
network pharmacology;
molecular docking;
flavonoids
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(12):202-209
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.
