Actovegin® reduces PMA-induced inflammation on human cells

Eur J Appl Physiol. 2020 Jul;120(7):1671-1680. doi: 10.1007/s00421-020-04398-2. Epub 2020 May 23.

Abstract

Purpose: The effect of Actovegin® was investigated on PMA- and LPS-induced human peripheral blood mononuclear cells (PBMCs).

Methods: PBMCs (1 × 106 cells/ml) from five blood donors (2 f, 3 m; 45-55 years) were grown in medium and exposed to Actovegin® in the presence or absence of PMA or LPS. Supernatants were collected to assess the concentration of cytokines (TNF-α, IL-1beta, IL-6 and IL-10). The reactive oxygen species (ROS) were assessed by a ROS-GloTM H2O2 assay.

Results: Stimulation of cells by PMA or LPS (without Actovegin®) significantly increased the secretion of IL-1beta, IL-6, IL-10 and TNF-α from PBMCs, compared to controls. Pre-treatment of cells with Actovegin® (1, 5, 25, 125 µg/ml) plus PMA significantly decreased the secretion of IL-1beta from PBMCs, compared to controls (PMA without Actovegin®). In contrast, addition of Actovegin® (1, 5, 25, 125 and 250 µg/ml) plus LPS did not alter the IL-1beta production, compared to controls (LPS without Actovegin®). TNF-α, IL-6 and IL-10 do not contribute to the reduction of inflammatory reactions with Actovegin®.

Conclusions: Actovegin® can reduce the PMA-induced IL-1beta release and the ROS production from PBMCs. These findings may help to explain the clinically known positive effects of Actovegin® on athletic injuries with inflammatory responses (e.g., muscle injuries, tendinopathies).

Keywords: Human PBMCs; IL1-beta; LPS; PMA; ROS; Sports.

MeSH terms

  • Cytokines / metabolism
  • Female
  • Heme / analogs & derivatives*
  • Heme / pharmacology
  • Humans
  • Hydrogen Peroxide / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Leukocytes, Mononuclear / drug effects*
  • Lipopolysaccharides / pharmacology*
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Heme
  • Actovegin
  • Hydrogen Peroxide