What is the clinical evidence from this study?

Study design: Other. Population: Rats or cell lines modeling ventricular remodeling after acute myocardial infarction. Intervention: Ling-Gui-Zhu-Gan Decoction (LGZGD) vs. Control or placebo. Primary outcome: Ventricular remodeling parameters and molecular markers of ROS/TXNIP/NLRP3 signaling pathway activation (p=P<0.01 for increased inflammatory response and ROS production with TMAO stimulation concentrations used in modeling).

What question did this study set out to answer?

To explore the cardioprotective mechanisms of Ling-Gui-Zhu-Gan Decoction in reducing hyperinflammation post-heart attack.

March 9, 2026

Cardioprotective Effects of Ling-Gui-Zhu-Gan Decoction Against Ventricular Remodeling after Acute Myocardial Infarction via ROS/TXNIP/NLRP3 Signaling

Q: What are the key findings of this study?

Ling-Gui-Zhu-Gan Decoction exhibited cardioprotective effects against ventricular remodeling after acute myocardial infarction by modulating ROS/TXNIP/NLRP3 signaling pathways as shown by significant inflammatory and oxidative stress marker changes at TMAO 400 μM concentration (P<0.01).

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

To explore the cardioprotective mechanisms of Ling-Gui-Zhu-Gan Decoction in reducing hyperinflammation post-heart attack.

Key Result

Ling-Gui-Zhu-Gan Decoction exhibited cardioprotective effects against ventricular remodeling after acute myocardial infarction by modulating ROS/TXNIP/NLRP3 signaling pathways as shown by significant inflammatory and oxidative stress marker changes at TMAO 400 μM concentration (P<0.01).

Key Points

To explore the cardioprotective mechanisms of Ling-Gui-Zhu-Gan Decoction in reducing hyperinflammation post-heart attack.
Identified LGZGD components using ultra-high performance liquid chromatography.
Established a rat model of ventricular remodeling after acute myocardial infarction.
Measured cardiac function and pathology through echocardiography and histopathological staining after treatment.
Conducted in vitro analysis using H9c2 cells with TMAO to evaluate oxidative stress and inflammatory markers.
LGZGD improved cardiac function and reduced myocardial pathology significantly.
Lowered serum levels of cardiac enzymes and TMAO, and decreased oxidative stress markers.
Regulated ROS/TXNIP/NLRP3 signaling pathway, reducing levels of proinflammatory cytokines IL-1β and IL-18 in vivo and in vitro.

Structured PICO

Does Ling-Gui-Zhu-Gan Decoction improve cardiac function and reduce myocardial injury in a rat model of ventricular remodeling after acute myocardial infarction?

Population

Rat model of ventricular remodeling after acute myocardial infarction (established by LAD ligation), n=24 (6 per group), and in vitro H9c2 cells exposed to 400 µmol/L TMAO.

Intervention

Ling-Gui-Zhu-Gan Decoction (LGZGD) 4.2 g/kg for 4 weeks

Comparator

Sham group, model group (untreated AMI), and captopril (4.375 mg/kg) group

Outcome

Cardiac function, histopathological changes, serum cardiac enzymes, oxidative stress markers, and inflammatory cytokinessurrogate

Ling-Gui-Zhu-Gan Decoction ameliorates TMAO-induced myocardial injury and ventricular remodeling after AMI by modulating the ROS/TXNIP/NLRP3 signaling pathway in a preclinical model.

Main Result

p-value: P<0.01 for increased inflammatory response and ROS production with TMAO stimulation concentrations used in modeling

Limitations

Study performed in vitro and animal models, limiting direct clinical applicability.
Exact sample sizes, intervention dosing, duration, and quantitative clinical outcomes were not reported.
Lack of randomized controlled clinical trial data.
No human subject demographic or clinical characteristic data provided.

Abstract

OBJECTIVE: To investigate the underlying mechanism of Ling-Gui-Zhu-Gan Decoction (LGZGD) in reducing hyperinflammatory responses to provide cardioprotective effects. METHODS: The main chemical components of LGZGD were identified using ultra-high performance liquid chromatography. In vivo, the rats were randomly divided into 4 groups using simple randomization: the sham group, the model group, the LGZGD (4.2 g/kg) group, and captopril (4.375 mg/kg) group, 6 in each group. A rat model of ventricular remodeling (VR) after acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment, cardiac function was evaluated by echocardiography, and histopathological changes were examined using HE and Masson stainings. Serum levels of cardiac enzymes and oxidative stress markers were measured with microplate assays. Reactive oxygen species (ROS) were visualized by fluorescence staining, while protein and mRNA levels were analyzed by Western blot and RT-qPCR. Levels of proinflammatory cytokines and trimethylamine N-oxide (TMAO) were quantified through ELISA. In vitro, H9c2 cells were exposed to 400 µmol/L TMAO, and oxidative stress markers were measured by microplate assay. ROS levels were visualized using fluorescence staining, and gene and protein expression were analyzed by RT-PCR and Western blot. Proinflammatory cytokines and TMAO levels were further evaluated by ELISA. RESULTS: LGZGD was found to contain liquiritin, isoliquiritin, coumarin, liquiritigenin, cinnamic acid, kaempferol, cinnamaldehyde, glycyrrhizic acid, and atractylenolide III. In vivo, LGZGD improved cardiac function, reduced myocardial pathology, lowered serum cardiac enzymes and TMAO, decreased oxidative stress, regulated the expression of genes and proteins within the ROS/thioredoxin-interacting protein (TXNIP)/NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) pathway, and suppressed the secretion of IL-1β and IL-18 (P<0.01). In vitro analysis showed that LGZGD significantly decreased markers of myocardial injury, alleviated oxidative stress, and inhibited the secretion of IL-1β and IL-18 in TMAO-stimulated H9c2 cells (P<0.01). CONCLUSION: LGZGD ameliorates TMAO-induced myocardial injury by modulating the ROS/TXNIP/NLRP3 signaling pathway.

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