The therapeutic efficacy of resveratrol for acute lung injury-A meta-analysis of preclinical trials

Abstract

Background: Resveratrol (RES) has a protective effect on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Our purpose was to conduct a meta-analysis to investigate the efficacy of RES for ALI/ARDS in animal models. Methods: PubMed, EMBASE and Web of Science were searched to screen relevant preclinical trials. The standardized mean difference (SMD) was used to compare the lung injury score, lung wet-dry weight ratio (W/D ratio), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, the number of neutrophils in bronchoalveolar lavage fluid (BALF) and the total protein in BALF between the treatment and control groups. SYRCLE's risk of bias tool was used for quality assessment. Results: A total of 17 studies published from 2005 to 2021 were included in our study to calculate the SMD with corresponding confidence interval (CI). As compared with controls, RES significantly decreased the lung injury score (SMD -2.06; 95% CI -2.77, -1.35; p < 0.00001) and W/D ratio (SMD -1.92; 95% CI -2.62, -1.22; p < 0.00001). RES also reduced the number of neutrophils in BALF (SMD -3.03; 95% CI -3.83, -2.24; p < 0.00001) and the total protein in BALF (SMD -5.59; 95% CI -10.10, -1.08; p = 0.02). Furthermore, RES was found to downregulate proinflammatory mediators such as TNF-α (SMD -2.02; 95% CI -3.09, -0.95; p = 0.0002), IL-1β (SMD -2.51; 95% CI -4.00, -1.02; p = 0.001) and IL-6 (SMD -2.26; 95% CI -3.49, -1.04; p = 0.0003). But RES had little effect on the anti-inflammatory mediators such as IL-10 (SMD 2.80; 95% CI -0.04, 5.63; p = 0.05). Sensitivity analysis and stratified analysis were performed for the outcome indicators with heterogeneity. Conclusion: RES treatment is effective on reducing the severity of ALI. However, more animal studies and human trials are needed for further investigation. Our study may provide a reference for preclinical and clinical studies in the future to some extent.

Keywords: acute lung injury; acute respiratory distress syndrome; animal models; meta−analysis; resveratrol.

FIGURE 1

PRISMA flow diagram for review and selection process of studies included in meta−analysis of RES in rodent models of ALI.

FIGURE 2

(A) Forest plot analyzing the effect of RES treatment of lung injury score. (B) Forest plot analyzing the effect of RES treatment of W/D ratio. (C) Forest plot analyzing the effect of RES treatment of IL−1β. (D) Forest plot analyzing the effect of RES treatment of IL−6.

FIGURE 3

(A) Forest plot analyzing the effect of RES treatment of TNF−α. (B) Forest plot analyzing the effect of RES treatment of IL−10. (C). Forest plot analyzing the effect of RES treatment of total protein in BALF. (D) Forest plot analyzing the effect of RES treatment of number of neutrophils in BALF.

FIGURE 4

(A) Sensitivity analysis of RES treatment of number of neutrophils in BALF. (B) Sensitivity analysis of RES treatment of lung injury score. (C) Sensitivity analysis of RES treatment of W/D ratio. (D) Sensitivity analysis of RES treatment of IL−1β. (E) Sensitivity analysis of RES treatment of IL−6. (F) Sensitivity analysis of RES treatment of TNF−α. (G) Sensitivity analysis of RES treatment of IL−10. (H) Sensitivity analysis of RES treatment of total protein in BALF.

FIGURE 5

(A) Forest plot analyzing the effect of RES treatment of TNF−α after removing studies with a large effect on heterogeneity. (B) Forest plot analyzing the effect of RES treatment of IL−10 after removing studies with a large effect on heterogeneity. (C) Forest plot analyzing the effect of RES treatment of total protein in BALF after removing studies with a large effect on heterogeneity.

FIGURE 6

(A) Funnel plots for RES treatment of lung injury score. (B) Trim−and−fill analysis of RES treatment of lung injury score. (C) Funnel plots for RES treatment of W/D ratio. (D) Trim−and−fill analysis of RES treatment of W/D ratio. (E) Funnel plots for RES treatment of IL−6.