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Remodeling the gut-heart axis: Danggui Sini granule mitigates vasospastic coronary heart disease via
Haipeng Tang1, Zhiliang Sun1, Shanshan Wang1
1School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, China.
Insights
Danggui Sini Granule (DSG) protects against coronary heart disease (CHD) by modulating gut microbiota, lipid metabolism, and inflammation pathways. This study reveals DSG
Area of Science:
- Cardiovascular Research
- Integrative Medicine
- Gut Microbiome Research
Background:
- Coronary heart disease (CHD) poses a significant global health challenge, with residual risk persisting despite current treatments.
- Danggui Sini Granule (DSG), derived from a traditional remedy, is clinically used for cardiovascular benefits, but its gut-heart axis mechanisms are unclear.
Purpose of the Study:
- To investigate the gut-heart axis mechanisms underlying the cardioprotective effects of Danggui Sini Granule (DSG) in a rat model of vasospastic coronary heart disease.
- To elucidate how DSG influences gut microbiota, host metabolism, and inflammatory pathways.
Main Methods:
- Established a vasospastic CHD rat model using a high-fat diet, stress, and pituitrin injection, followed by DSG treatment.
- Evaluated therapeutic effects via ECG, histopathology, serum lipids, and inflammatory markers.
- Analyzed gut microbiota using 16S rRNA sequencing and serum metabolites via untargeted metabolomics.
- Employed network pharmacology and joint pathway enrichment to integrate multi-omics data and identify key mechanisms.
Main Results:
- DSG treatment attenuated cardiac injury, improved lipid profiles, and reduced inflammatory markers (TNF-α, IL-6).
- DSG modulated gut microbiota, decreasing pathogenic bacteria and increasing beneficial genera like Lactobacillus.
- Metabolomics identified restoration of protective lipid mediators and highlighted alterations in linoleic and arachidonic acid pathways.
- Integrated analysis prioritized lipid metabolism, vascular protection, and inflammation pathways, with molecular docking supporting interactions between DSG components and key targets.
Conclusions:
- DSG exerts cardioprotective effects in vasospastic CHD by orchestrating gut microbiota shifts, lipid metabolism reprogramming, and anti-inflammatory actions.
- The findings provide a comprehensive, gut-heart-axis-based framework for understanding DSG's therapeutic potential.
- Future studies are needed to confirm causal relationships identified through multi-omics and in silico analyses.
Background:
Coronary heart disease (CHD) remains a major global health burden, and residual cardiovascular risk persists despite guideline-based therapies. Danggui Sini Granule (DSG), a granule formulation derived from the classical Danggui Sini Decoction, has been widely used clinically to improve cardiovascular circulation and alleviate ischemic symptoms; however, its gut-heart-axis-related mechanisms remain insufficiently defined.
Methods:
A rat model of vasospastic CHD was established using a high-fat diet combined with acute environmental stress and pituitrin injection, followed by treatment with DSG at different doses. Pharmacodynamic effects were evaluated by electrocardiography, histopathology, serum lipids, and inflammatory markers. Gut microbial alterations were profiled using 16S rRNA sequencing. Serum metabolic changes were characterized by untargeted metabolomics. Network pharmacology and joint pathway enrichment were further used to cross-validate target prediction with metabolite-level readouts and to prioritize gut-microbiota-metabolism-phenotype links.
Results:
DSG attenuated ST-segment elevation, reduced myocardial histopathological injury, mitigated dyslipidemia, and lowered systemic inflammatory mediators, including TNF-α and IL-6. 16S rRNA analysis showed bidirectional microbiota modulation, with reduced opportunistic/pathogenic genera (e.g., Escherichia, Staphylococcus) and enrichment of potentially beneficial taxa (e.g., Lactobacillus, Clostridium). Metabolomics revealed partial mitigation of CHD-related disturbances, mainly in linoleic acid and arachidonic acid pathways, with restoration of levels of protective lipid mediators including 12,13-DHOME, 3-HIA, and PGE1. Joint pathway analysis integrating reversed metabolites with predicted targets consistently prioritized Lipid and atherosclerosis, PPAR-related metabolic regulation, PI3K-Akt/eNOS-associated vascular protection, and inflammation-related signaling (JAK-STAT and TNF/NF-κB). Furthermore, molecular docking suggested favorable binding affinities between the key components/metabolites (e.g., Quercetin, 12,13-DHOME, PGE1) and core targets within these pathways (including PIK3CA, NOS3, PPARG, TNF, and RELA).
Conclusion:
DSG demonstrated significant cardioprotective effects in vasospastic CHD rats, which were associated with coordinated gut microbiota remodeling, lipid-metabolic reprogramming, and modulation of inflammation-related pathways. These findings, further suggested by in silico molecular docking, provide a multidimensional framework for understanding the cardioprotective potential of DSG from a gut-heart-axis perspective. Given the associative nature of the current multi-omics data, key causal links should be validated in future targeted intervention studies.
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