Actovegin® reduces PMA-induced inflammation on human cells

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).

PRISMA Systematic Literature Review, including with Meta-Analysis vs. Chatbot/GPT (AI) regarding Current Scientific Data on the Main Effects of the Calf Blood Deproteinized Hemoderivative Medicine (Actovegin) in Ischemic Stroke

“…Recently, the effect of Actovegin ® on the release of inflammatory cytokines IL-1β, IL-6, IL-10, and TNF-α was investigated, revealing its potential to support antioxidative systems in cells. Furthermore, Actovegin ® demonstrated a dose-dependent reduction in the release of pro-inflammatory interleukin Il-1 β in human peripheral blood mononuclear cells, potentially due to a specific effect on B cells [ 9 ].…”

“…Furthermore, Actovegin ® showed anti-inflammatory properties by reducing lipopolysaccharides and Phorbol 12-myristate 13-acetate (PMC)-induced reactive oxygen species (ROS), which may contribute to the formation and function of an efficient antioxidative and/or anti-inflammatory system in cells, thus reducing the consequences of inflammation. These findings may help in understanding the positive effects of Actovegin on inflammatory lesions [ 9 ].…”

“…Actovegin primarily acts on various aspects of the ischemic stroke lesion constellation, with a focus on tissue oxidation [ 7 ], energy metabolism [ 8 ], and glucose availability [ 9 ]. It elevates these factors, combating ischemic processes and oxidative stress [ 10 ].…”

Phorbol-12-myristate-13-acetate is a potent enhancer of B cells with a granzyme B+ regulatory phenotype

“…Based on the effects described and a longer half-life of PMA compared with DAG, a pronounced and extended potency of PMA to induce GraB cells could be expected if applied systemically. On the other hand, the release of further cytokines including IL-4, IL-6, IL-8, TNF-α, and IFN-γ upon in-vivo application of PMA must be considered as well ( 46 – 48 ). The consequences were observed in a clinical trial in 1998 ( 49 , 50 ).…”

<p>The Effect of Inflammation on the Healing Process of Acute Skin Wounds Under the Treatment of Wounds with Injections in Rats</p>

“…[24][25][26][27][28] Deproteinized Calf Blood Medicine (Actovegin ® preparation) is used in everyday clinical practice as it significantly affects regional blood flow and the intensity of local inflammation. [29][30][31][32][33] Collagen I type (Collost ® ) does not significantly affect inflammation but is effective as a wound healing stimulator. [34][35][36][37][38][39]…”