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Open Access 25-10-2022 | Dexamethasone | Original Article

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

Authors: Wojciech Szlasa, Sylwester Ślusarczyk, Izabela Nawrot-Hadzik, Renata Abel, Aleksandra Zalesińska, Anna Szewczyk, Natalia Sauer, Robert Preissner, Jolanta Saczko, Marcin Drąg, Marcin Poręba, Małgorzata Daczewska, Julita Kulbacka, Małgorzata Drąg-Zalesińska

Published in: Inflammation | Issue 2/2023

Abstract

Betulin is a heavily studied natural compound for its use as an anticancer or pro-regenerative agent. The structural similarity between betulin to steroids gives rise to the idea that the substance may as well act as an anti-inflammatory drug. This study is the first to describe the anti-inflammatory properties of betulinic acid, betulin, and its derivatives with amino acids 1,4-diaminebutane (Dab), 1,3-diaminepropane (Dap), Ornithine (Orn), and lysine (Lys) on murine macrophages from lymphoma site. The compounds were compared to dexamethasone. To establish the response of the macrophages to the natural compounds, we tested the viability as well as sensitivity to the inflammatory signaling (IFNγR). IL-6 secretory properties and HSP-70 content in the cells were examined. Furthermore, we characterized the effects of compounds on the inhibition of cyclooxygenase-2 (COX-2) activity both in the enzymatic assays and molecular docking studies. Then, the changes in COX-2 expression after betulin treatment were assessed. Betulin and betulinic acid are the low-cytotoxicity compounds with the highest potential to decrease inflammation via reduced IL-6 secretion. To some extent, they induce the reorganization of IFNγR with nearly no effect on COX-2 activity. Conversely, Bet-Orn and Bet-Lys are highly cytotoxic and induce the aggregation of IFNγR. Besides, Bet-Lys reduces the activity of COX-2 to a higher degree than dexamethasone. Bet-Orn is the only one to increase the HSP-70 content in the macrophages. In case of IL-6 reduction, all compounds were more potent than dexamethasone.

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Title: Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages
Authors: Wojciech Szlasa
Sylwester Ślusarczyk
Izabela Nawrot-Hadzik
Renata Abel
Aleksandra Zalesińska
Anna Szewczyk
Natalia Sauer
Robert Preissner
Jolanta Saczko
Marcin Drąg
Marcin Poręba
Małgorzata Daczewska
Julita Kulbacka
Małgorzata Drąg-Zalesińska
Publication date: 25-10-2022
Publisher: Springer US
Keyword: Dexamethasone
Published in: Inflammation / Issue 2/2023
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-022-01756-4

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