The Natural Combination Medicine Traumeel (Tr14) Improves Resolution of Inflammation by Promoting the Biosynthesis of Specialized Pro-Resolving Mediators.

Paul M Jordan,Virginie Gavioli,Kathrin Hemmer,Natascha Krömmelbein,Yvonne Burmeister,Bernd Seilheimer,Vincent Baillif,Marc Dubourdeau,Oliver Werz,Andrea M Müller,Emeline Van Goethem

doi:10.3390/ph14111123

Abstract

The resolution of inflammation is an integral part of the acute inflammatory response and eventually leads to the return to homeostasis. It is supported by specialized pro-resolving mediators (SPMs) that act as immunoresolvents via specific G-protein-coupled receptors. In contrast to classical non-steroidal anti-inflammatory drugs (NSAIDs) that suppress the formation of pro-inflammatory lipid mediators such as prostaglandins, novel pharmacotherapeutic concepts propose to foster the biosynthesis of beneficial SPMs. Here, we demonstrate that the natural combination medicine Traumeel (Tr14) improves resolution of inflammation by promoting SPM formation. Tr14 enhanced the biosynthesis of 12-/15-lipoxygenase (LOX) products and of SPMs in zymosan-induced mouse peritonitis as well as in human monocyte-derived macrophages challenged with Staphylococcus aureus. Importantly, in the peritonitis model, Tr14 supported the recruitment of innate leukocytes and the efferocytotic capacity of macrophages, and positively influenced the inflammation resolution index. Taken together, we suggest that based on these properties Tr14 may possess therapeutic potential as an enhancer for the resolution of inflammatory processes.

Highlights

Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popular medicines and are widely used as analgesics and for reducing inflammation [1]
The infiltrate was predominantly composed of polymorphonuclear leukocytes (PMNs) that were significantly decreased in numbers by the low dose of Tr14 at 8 h (Figure 1C, Figure S2A)
We found that in a mouse model of self-resolving inflammation triggered by zymosan in vivo, Tr14 did not consistently inhibit pro-inflammatory actions, such as recruitment of PMNs, release of cytokines or production of LTs and PGs, which contrasts with classical NSAIDs [1]

Summary

Introduction

Non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popular medicines and are widely used as analgesics and for reducing inflammation [1]. Despite their efficacy in alleviating pain and inflammatory reactions, NSAIDs exert adverse gastrointestinal, cardiovascular, and renal effects [2], and they are essentially inefficient at promoting resolution and tissue repair [3]. The resolution of inflammation is part of the inflammatory process that actively terminates inflammation and leads to tissue repair and regeneration [6]. The proinflammatory LMs are comprised of leukotrienes (LTs) and prostaglandins (PGs) produced

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