Multi-Omics and Experimental Validation Reveal the Protective Effect of Paeoniflorin Against Coronary Heart Disease in Mice via Inhibiting the C3-Cfd-C3aR Pathway

Q: What are the key findings of this study?

Paeoniflorin significantly improved cardiac function and alleviated myocardial injury in a mouse model of coronary heart disease by inhibiting the C3-Cfd-C3aR pathway.

Q: What is the clinical evidence from this study?

Population: Coronary heart disease (n=100). Intervention: Paeoniflorin vs. Model group (purified water). Primary outcome: Cardiac function and myocardial injury (p=<0.05).

Q: What does this research mean for the field?

Paeoniflorin improves cardiac function and attenuates myocardial injury in coronary heart disease model mice by inhibiting the C3-Cfd-C3aR signaling pathway. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To investigate the protective effects and molecular mechanisms of paeoniflorin against coronary heart disease using a mouse model combined with multi-omics profiling.

Yi Yang; Xiang Li; Wenjing Zong; Sijia Wu; Yingying Li; Tang Danli; Haitao Zhang

doi:10.3390/ijms27146236

July 13, 2026International Journal of Molecular SciencesOpen Access

Multi-Omics and Experimental Validation Reveal the Protective Effect of Paeoniflorin Against Coronary Heart Disease in Mice via Inhibiting the C3-Cfd-C3aR Pathway

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Key result

Paeoniflorin improves cardiac function and reduces myocardial injury in mice by inhibiting C3-Cfd-C3aR signaling.

P<0.05
n=100

Figures

Why the study?

Paeoniflorin has shown potential in cardiovascular protection, but its specific anti-coronary heart disease molecular targets and systematic regulatory networks remain unclear.

Does paeoniflorin improve cardiac function and alleviate myocardial injury in a mouse model of coronary heart disease?

Key Points

To investigate the protective effects and molecular mechanisms of paeoniflorin against coronary heart disease using a mouse model combined with multi-omics profiling.
Coronary heart disease (CHD) was established in mice, followed by treatment with low-, medium-, and high-dose paeoniflorin or metoprolol tartrate.
Plasma samples underwent label-free quantitative proteomics and untargeted metabolomics, accompanied by histological evaluation, echocardiography, and molecular docking.
Paeoniflorin significantly improved left ventricular ejection fraction and fractional shortening, while reducing serum levels of CK, AST, LDH, CK-MB, TC, TG, and LDL-C (p < 0.05).
Proteomic analysis revealed 51 reversed differentially expressed proteins, with paeoniflorin significantly downregulating C3, Cfd, C3aR, BTK, IL-1β, TNF-α, Caspase-3, and ITGA2B/ITGB3 (p < 0.05).
Metabolomic profiling identified 57 abnormal metabolites reversed by paeoniflorin, which directly correlated with reduced cardiomyocyte apoptosis and myocardial fibrosis.

Structured PICO

Does paeoniflorin improve cardiac function and alleviate myocardial injury in a mouse model of coronary heart disease?

P

Population

100 female ApoE-/- mice subjected to high-fat diet and coronary artery ligation to model coronary heart disease, treated with varying doses of paeoniflorin for 4 weeks.

I

Intervention

Paeoniflorin (PA) administered intragastrically daily for 4 consecutive weeks at low (25 mg/kg), medium (50 mg/kg), or high (100 mg/kg) doses.

C

Comparator

Model group (intragastrically administered an equal volume of purified water daily) and active comparator metoprolol tartrate (MT, 1.3 mg/kg).

O

Outcome

Cardiac function (EF, FS, LVESV/LVEDV, LVESD/LVEDD), myocardial injury markers, pathological changes, and multi-omics (proteomic and metabolomic) profiles.surrogate

Main Result

p-value: p=<0.05

Paeoniflorin protects against coronary heart disease in a mouse model by targeting the C3-Cfd-C3aR pathway to inhibit inflammation, apoptosis, and platelet activation.

Limitations

Experiments were conducted exclusively in a mouse model, without validation using human clinical samples.
The sample size for Western blot validation was limited (n = 3 per group).
Molecular docking merely predicts potential binding without direct physical interaction evidence.
Interpretation of PA-induced antiplatelet activity is only supported by myocardial ITGA2B and ITGB3 expression changes, without complementary platelet functional assays.

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Implication

Paeoniflorin may protect against myocardial injury in mouse models; hypothesis-generating for C3-Cfd-C3aR inhibition in human coronary disease.

Abstract

Coronary heart disease (CHD) is a global cardiovascular disease with high morbidity and mortality, and its complex pathological mechanism poses great challenges to clinical prevention and treatment. Paeoniflorin (PA), a monoterpene glycoside active ingredient from Ranunculaceae plants, has shown potential in cardiovascular protection, but its specific anti-CHD molecular targets and systematic regulatory networks remain unclear. In this study, a mouse model of CHD was established, and a multi-omics strategy combining label-free quantitative proteomics and metabolomics was adopted to explore the mechanism of PA in treating CHD. The results showed that PA significantly improved cardiac function, alleviated myocardial pathological injury and fibrosis, and regulated lipid metabolism in CHD model mice, with the high-dose group showing the optimal effect. Proteomic analysis identified 51 key differentially expressed proteins (DEPs) reversed by PA, which were mainly enriched in complement and coagulation cascades, and neutrophil extracellular trap formation pathways, with the C3-Cfd-C3aR signaling axis as the core hub. Further verification confirmed that PA could downregulate the expression of C3, Cfd, C3aR, and their downstream molecule BTK, thereby inhibiting myocardial inflammatory response and cardiomyocyte apoptosis. In addition, PA downregulated the expression of platelet activation markers ITGA2B/ITGB3. Metabolomic analysis revealed that PA reversed 57 abnormal metabolites in CHD mice, which were enriched in GABAergic synapse, retrograde endocannabinoid signaling and other pathways. Molecular docking confirmed that PA could stably bind to C3, Cfd, C3aR, BTK, and ITGA2B/ITGB3 with strong binding activity. In conclusion, PA exerts anti-CHD effects through a multi-target and multi-pathway synergism, mainly by targeting the C3-Cfd-C3aR axis to inhibit inflammation, apoptosis and platelet activation, and regulating metabolic disorders. This study provides experimental evidence and theoretical support for the clinical application of PA as a multi-target therapeutic drug for CHD.

Discussion

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Cite This Study

Yang et al. (2026) studied Coronary heart disease (n=100). Paeoniflorin vs. Model group (purified water) was evaluated on Cardiac function and myocardial injury (p=<0.05). Paeoniflorin significantly improved cardiac function and alleviated myocardial injury in a mouse model of coronary heart disease by inhibiting the C3-Cfd-C3aR pathway.

synapsesocial.com/papers/6a5600ff10535b590d162474 https://doi.org/10.3390/ijms27146236

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Multi-Omics and Experimental Validation Reveal the Protective Effect of Paeoniflorin Against Coronary Heart Disease in Mice via Inhibiting the C3-Cfd-C3aR Pathway

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Multi-Omics and Experimental Validation Reveal the Protective Effect of Paeoniflorin Against Coronary Heart Disease in Mice via Inhibiting the C3-Cfd-C3aR Pathway

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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