The effects of apigenin administration on the inhibition of inflammatory responses and oxidative stress in the lung injury models: a systematic review and meta-analysis of preclinical evidence

Abstract

Background/objective: Apigenin is a member of the flavonoid family that can regulate various biological processes, which is characterized as a treatment of different inflammatory disorders and pathological problems associated with oxidative stress (OS). Recent research has focused on apigenin immunomodulatory properties as a potential treatment for different types of lung injuries. This meta-analysis was designed to determine the impact of apigenin treatment on inflammatory markers and OS parameters in animal models of lung injuries.

Methods: The comprehensive literature search was conducted using electronic databases such as Google Scholar, PubMed, Web of Science, Scopus, and Embase up to August 2021. To assess apigenin's effect on inflammatory mediators and OS biomarkers in lung injury animal models, we used the I² statistic to determine the heterogeneity. We then pooled data as standardized mean difference (SMD) with a 95% confidence interval (CI).

Results: Our meta-analysis of the pooled data for inflammatory biomarkers demonstrated that the apigenin administration significantly decreased the NF-κB expression (SMD - 1.60, 95% CI [- 2.93 to - 0.26]; I² = 89.0%, p < 0.001), IL-1β (SMD - 4.30, 95% CI [- 6.24 to - 2.37]; I² = 67.3%, p = 0.047), IL-6 (SMD - 4.10, 95% CI [- 5.04 to - 3.16]; I² = 72.6%, p < 0.001), TNF-α (SMD - 3.74, 95% CI [- 4.67 to - 2.82]; I² = 84.1%, p < 0.001), and TNF-α gene expression (SMD - 3.44, 95% CI [- 4.44 to - 2.43]; I² = 0.0%, p = 0.622). This study also indicated the efficacy of apigenin in increasing the level of CAT (SMD 4.56, 95% CI [3.57 to 5.55]; I² = 15.3%, p = 3.15), GSH (SMD 5.12, 95% CI [3.53 to 6.70]; I² = 77.6%, p < 0.001), and SOD (SMD 3.45, 95% CI [2.50 to 4.40]; I² = 79.2%, p < 0.001), and decreasing the level of MDA (SMD - 3.87, 95% CI [- 5.25 to - 2.49]; I² = 80.3%, p < 0.001) and MPO (SMD - 4.02, 95% CI [- 5.64 to - 2.40]; I² = 88.9%, p < 0.001), TGF- β (SMD - 3.81, 95% CI [- 4.91 to - 2.70]; I² = 73.4%, p = 0.001) and W/D level (SMD - 3.22, 95% CI [- 4.47 to - 1.97]; I² = 82.1%, p < 0.001) than control groups.

Conclusion: Overall, our findings showed the immunomodulatory potential of apigenin as an alternative treatment for the suppression of inflammatory responses and OS in different types of lung injury diseases. Nevertheless, due to the paucity of clinical studies, reliable preclinical models, and clinical settings, evaluating the influence of apigenin on lung injury is required in the future. Before conducting large-scale clinical trials, detailed human pharmacokinetic studies are also needed to establish dosage ranges and determine the initial safety and tolerability of apigenin.

Keywords: Acute lung injury (ALI); Apigenin; Inflammation; Lung fibrosis; Meta-analysis; Oxidative stress (OS).