Effect of emodin on acute lung injury: a meta-analysis of preclinical trials

Background

Emodin has protective effects on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). This meta-analysis intended to illustrate the efficacy of emodin on ALI/ARDS animal models.

Methods

Relevant preclinical studies were searched on PubMed, EMBASE, and Web of Science. Standardized mean differences (SMDs) with corresponding confidence intervals (CIs) were used to compare lung injury scores, lung wet-to-dry weight ratios (W/D), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-18, PaO₂, and PaCO₂ between the treatment and control groups. The article quality was appraised using the SYRCLE tool.

Results

Twenty one studies published between 2014 and 2023 were enrolled. Compared with the control group, emodin significantly reduced lung injury scores (SMD: -3.63; 95% CI: -4.36, -2.90; p < 0.00001), W/D ratios (SMD: -3.23; 95% CI: -4.29, -2.16; p < 0.00001), and MPO levels (SMD: -2.96; 95% CI: -3.92, -1.99; p < 0.00001). Furthermore, emodin downregulated TNF-α (SMD: -3.04; 95% CI: -3.62, -2.47; p < 0.00001), IL-1β (SMD: -3.76; 95% CI: -4.65, -2.87; p < 0.00001), IL-6 (SMD: -3.19; 95% CI: -3.95, -2.43; p < 0.00001), and IL-18 levels (SMD: -4.83; 95% CI: -6.10, -3.57; p < 0.00001). Emodin improved gas exchange dysfunction, increased PaO₂ (SMD: 3.76; 95% CI: 2.41, 5.11; p < 0.00001), and decreased PaCO₂ (SMD: -3.83; 95% CI: -4.90, -2.76; p < 0.00001). Sensitivity analyses and stratified analyses were conducted for outcome measures with heterogeneity.

Conclusions

Emodin treatment can effectively reduce the severity of ALI in animal models. Additional animal investigations and clinical trials involving human subjects are imperative.

Key Points:

1. Emodin’s Mechanism of Action: Reduces inflammation, oxidative stress, and neutrophil accumulation, alleviating ALI pathophysiology.
2. Reduction in Inflammatory Markers: Downregulates TNF-α, IL-1β, IL-6, and IL-18, mitigating inflammatory responses that exacerbate ALI.
3. Improved Gas Exchange: Enhances oxygenation (PaO2) and reduces hypercapnia (PaCO2), addressing respiratory dysfunction in ALI.
4. Preclinical Evidence: Analysis of 21 studies shows consistent improvements in lung injury scores and pulmonary edema markers like wet-to-dry ratios (W/D).
5. Therapeutic Dose Range: Effective at doses between 10-700 mg/kg with both preventive and post-ALI treatments showing efficacy.
6. Variability in Models: Effects were robust across various ALI models, including lipopolysaccharide-induced and ischemia-reperfusion injury.
7. Safety Profile: Animal studies report no significant adverse effects, supporting emodin’s potential translational viability.
8. Potential as an Adjunctive Therapy: Could complement existing treatments by targeting inflammatory pathways and promoting alveolar stability.
9. Research Gaps: High heterogeneity in study designs necessitates standardization for future preclinical and clinical research.
10. Clinical Relevance: Highlights the need for clinical trials to explore emodin’s safety and efficacy in treating human ALI/ARDS.

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