Effects of Standardized Brazilian Green Propolis Extract (EPP-AF®) on Inflammation in Haemodialysis Patients: A Clinical Trial

Abstract

Background: Patients on haemodialysis (HD) present a significant inflammatory status, which has a pronounced negative impact on their outcomes. Propolis is a natural resin with anti-inflammatory and immunomodulatory properties. We assessed the safety and impact of a standardized Brazilian green propolis extract (EPP-AF®) on the inflammatory status in patients under conventional HD.

Methods: Patients were assigned to receive 200 mg/day of EPP-AF® for 4 weeks followed by 4 weeks without the drug, and changes in plasma levels of interleukins (ILs), interferon gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), and high-sensitivityc-reactive protein (HsCRP) were measured. A heatmap was used to illustrate trends in data variation.

Results: In total, 37 patients were included in the final analysis. Patients presented an exacerbated inflammatory state at baseline. During EPP-AF® use, there was a significant reduction in IFN-γ (p=0.005), IL-13 (p=0.04 2), IL-17 (p=0.039), IL-1ra (p=0.008), IL-8 (p=0.009), and TNF-α (p < 0.001) levels compared to baseline, and significant changes were found in Hs-CRP levels. The heatmap demonstrated a pattern of pronounced proinflammatory status at baseline, especially in patients with primary glomerulopathies, and a clear reduction in this pattern during the use of EPP-AF®. There was a tendency to maintain this reduction after suspension of EPP-AF®. No significant side effects were observed.

Conclusion: Patients under haemodialysis presented a pronounced inflammatory status, and EPP-AF® was demonstrated to be safe and associated with a significant and maintained reduction in proinflammatory cytokines in this population. This trial is registered with Clinicaltrials.gov NCT04072341.

Figure 1

Flow diagram of study participants.

Figure 2

Inflammatory parameters of patients in the periods studied. ^∗p <  0.05. ^∗∗p <  0.001.

Figure 3

Heatmap demonstrating the inflammation profile of patients in the measured periods. The heatmap (a) shows data for the mean plasma concentration of each indicated marker per time point, and the data were log-transformed and Z score normalized. This approach was used to illustrate trends in data variation. A hierarchical cluster analysis (Ward's method with 100X bootstrap) was used to group the biomarkers with similar distributions between the time points. Dendrograms represent Euclidean distance. The red and blue colours demonstrate a higher and lower inflammatory pattern, respectively. The fold differences between the indicated means were calculated, and log10 values were plotted (b). Differences between each time point were examined using the Wilcoxon matched paired test. Red bars indicate mediators that were significantly different between the groups.

Figure 4

Heatmap demonstrating the inflammatory profile of patients according to the main aetiologies of kidney disease. The heatmap shows data for the mean plasma concentration of each indicated marker according to the main aetiologies of kidney disease, and the data were log-transformed and Z score normalized. A hierarchical cluster analysis (Ward's method with 100X bootstrap) was used to group the biomarkers with similar distributions between the time points. Dendrograms represent Euclidean distance. DM: diabetes mellitus; GP: glomerulopathies; SAH: systemic arterial hypertension.