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Mechanistic Insights Into Qidan Yixin Decoction for Diabetic Cardiomyopathy via Macrophage Polarization
Yi Liu1, Juan Zhang2, Wei Gao2
1The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
Insights
Qidan Yixin decoction (QDYXD) improves diabetic cardiomyopathy (DCM) by reducing M1 macrophage polarization and inhibiting the HIF-1 pathway. This traditional Chinese medicine modulates key targets like LDHA and PGK1, enhancing cardiac function in DCM rats.
Area of Science:
- Integrative Medicine and Pharmacology
- Cardiovascular Research
- Immunology and Inflammation
Background:
- Diabetic cardiomyopathy (DCM) presents a complex etiology with limited therapeutic options.
- Qidan Yixin decoction (QDYXD) shows promise in clinical DCM treatment, but its mechanisms remain largely unelucidated.
- Understanding QDYXD's molecular targets is crucial for optimizing DCM management.
Purpose of the Study:
- To elucidate the underlying mechanisms of Qidan Yixin decoction (QDYXD) in treating diabetic cardiomyopathy (DCM).
- To identify the active components and molecular targets of QDYXD.
- To investigate the effects of QDYXD on macrophage polarization and cardiac function in DCM.
Main Methods:
- Network pharmacology was employed to identify QDYXD's active ingredients and targets.
- Bioinformatic analyses (GeneCards, GEO, GO, KEGG, PPI) and machine learning (SVM-RFE, LASSO, random forest) were used to pinpoint core targets.
- Experimental validation involved creating rat models of DCM and assessing cardiac function, macrophage polarization, and target gene expression (PGK1, LDHA, HIF1A).
Main Results:
- Network pharmacology identified 48 potential targets and key active components including quercetin, methyl palmitate, luteolin, and tanshinone IIA.
- Enrichment analyses highlighted the HIF-1 signaling pathway, and machine learning identified LDHA and PGK1 as core targets.
- Experimental results showed QDYXD suppressed PGK1, LDHA, and HIF1A upregulation, inhibited M1 macrophage polarization, and improved cardiac function in DCM rats.
Conclusions:
- QDYXD ameliorates DCM by attenuating M1 macrophage polarization and inhibiting the HIF-1 signaling pathway via modulation of PGK1, LDHA, and HIF1A.
- This study provides mechanistic insights into QDYXD's therapeutic effects on DCM, particularly its impact on macrophage polarization.
- The identified active components and core targets offer potential avenues for novel drug development in DCM therapy.
Abstract:
Background: Diabetic cardiomyopathy (DCM) has a multifactorial etiology, and no specific treatment is available for its management. Qidan Yixin decoction (QDYXD) demonstrated encouraging clinical results in treating DCM; however, its underlying mechanics are yet unclear. Methods: Network pharmacology was applied to determine the active ingredients and targets of QDYXD. The GeneCards and GEO databases were used to retrieve genes associated with DCM and macrophage polarization. These targets were subjected to GO and KEGG enrichment analyses, immune infiltration study, and PPI network design. The core targets were further refined using SVM-RFE, LASSO, and random forest algorithms. Docking the core targets with the main active components followed. For experimental validation, rat models were created. Results: There were 48 potential targets in all. Quercetin, methyl palmitate, luteolin, and tanshinone IIA were identified as the primary active components. Enrichment analysis indicated that one of the key pathways associated with the potential targets was the signaling pathway of HIF-1. Machine learning techniques were used to identify two core targets, LDHA and PGK1. Animal experiments demonstrated that QDYXD can suppress the upregulation of PGK1, LDHA, and HIF1A; block the polarization of M1 macrophages; and considerably enhance DCM rats' cardiac function. Conclusion: QDYXD improves cardiac function in DCM by attenuating M1 macrophage polarization and inhibiting the HIF-1 signaling pathway, specifically through the modulation of PGK1, LDHA, and HIF1A. This study provides preliminary insights into how QDYXD modulates macrophage polarization during DCM treatment. Moreover, the identification of potential active components and core molecular targets of QDYXD offers promising directions for future drug development in DCM therapy.
