25MODE OF ACTION

Traumeel® may stimulate a switch from pro-inflammatory mediators towards pro-resolving mediators both in vitro (human macrophages) and in vivo (murine model).[Jordan 2021]

Traumeel® significantly increased macrophage recruitment. Macrophages are needed to remove debris and neutrophils from the

inflamed site. Increase in the number of macrophages is believed to have a positive impact

on resolution. Is in alignment with shortened neutrophil resolution interval.

Traumeel® stimulated the synthesis of proresolving mediators: LXA4, RvD2, RvD5, MaR1 and PD1. Proresolving mediators are the mediators produced as part of the lipid

mediator class switch, a hallmark of the resolution phase. Their proresolving function is exerted via several mechanisms and includes effects on:

Neutrophils: reduction of PMN (polymorphonuclear leukocyte) infiltration, increased PMN apoptosis.

Macrophages: improved efferocytosis and phagocytosis, non-phlogistic monocyte recruitment and reprogramming towards anti-inflammatory and proresolving phenotypes.

Zymosan-induced peritonitis model Actions of Traumeel®[Jordan 2021]

Traumeel® promotes resolution of inflammation by increasing specialized pro-resolving mediators (SPM) levels and by enhancing macrophage efferocytosis as well as by shortening the resolution interval in an animal model. Shortened the neutrophil resolution interval by 5.9 hours. Significantly increased macrophage recruitment.

ATLAS OF INFLAMMATION RESOLUTION (AIR)

Recently, an Atlas of Inflammation Resolution (AIR) was created by Heel, together with Rostock University and Harvard Medical School researchers, providing the most detailed understanding of acute inflammation and inflammation resolution to date. The AIR is a comprehensive web-based resource describing all molecules involved in inflammation and its resolution, their interactions, and, most importantly, underlying cardinal processes. It is connected to many public scientific databases such as UniProt, GenBank, and Pubmed, and serves as a portal to these databases. This allows identifying any element on the map, its literature source, and using these databases for drug target identification. [https://www.sbi.uni-rostock.de/research/projects/ detail/62]. The AIR is published in Molecular Aspects of Medicine 2020[Serhan 2020]