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CC BY-NC-ND 4.0 · Planta Med 2024; 90(07/08): 546-553
DOI: 10.1055/a-2240-7462
Biological and Pharmacological Activity
Original Papers

Increased Glycolytic Activity Is Part of Impeded M1(LPS) Macrophage Polarization in the Presence of Urolithin A[ # ]

Sheyda Bahiraii
1   Department of Pharmaceutical Sciences/Pharmacognosy, University of Vienna, Vienna, Austria
2   Vienna Doctoral School of Pharmaceutical, Nutritional and Sport Sciences, University of Vienna, Vienna, Austria
,
Barbara Braunböck-Müller
1   Department of Pharmaceutical Sciences/Pharmacognosy, University of Vienna, Vienna, Austria
,
Elke H. Heiss
1   Department of Pharmaceutical Sciences/Pharmacognosy, University of Vienna, Vienna, Austria
› Author AffiliationsThis work was financed by the Austrian Science Fund FWF (P32600 to EHH).
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Abstract

Urolithin A is a gut metabolite of ellagitannins and reported to confer health benefits, e.g., by increased clearance of damaged mitochondria by macroautophagy or curbed inflammation. One targeted cell type are macrophages, which are plastic and able to adopt pro- or anti-inflammatory polarization states, usually assigned as M1 and M2 macrophages, respectively. This flexibility is tightly coupled to characteristic shifts in metabolism, such as increased glycolysis in M1 macrophages, and protein expression upon appropriate stimulation. This study aimed at investigating whether the anti-inflammatory properties of urolithin A may be driven by metabolic alterations in cultivated murine M1(lipopolysaccharide) macrophages. Expression and extracellular flux analyses showed that urolithin A led to reduced il1β, il6, and nos2 expression and boosted glycolytic activity in M1(lipopolysaccharide) macrophages. The pro-glycolytic feature of urolithin A occurred in order to causally contribute to its anti-inflammatory potential, based on experiments in cells with impeded glycolysis. Mdivi, an inhibitor of mitochondrial fission, blunted increased glycolytic activity and reduced M1 marker expression in M1(lipopolysaccharide/urolithin A), indicating that segregation of mitochondria was a prerequisite for both actions of urolithin A. Overall, we uncovered a so far unappreciated metabolic facet within the anti-inflammatory activity of urolithin A and call for caution about the simplified notion of increased aerobic glycolysis as an inevitably proinflammatory feature in macrophages upon exposure to natural products.

Key words

urolithin A - anti-inflammatory - macrophages - M1 polarization - glycolysis

# This work is dedicated to Professors Rudolf Bauer, Chlodwig Franz, Brigitte Kopp, and Hermann Stuppner for their invaluable contributions and commitment to Austrian Pharmacognosy.


Supporting Information

    Experimental protocols and data regarding the influence of UroA on cell viability, expression of M1(LPS), M2(IL4) markers, or glycolytic enzymes as well as on cellular glucose uptake rates are available as Supporting Information.

  • Supporting Information


Publication History

Received: 13 September 2023

Accepted after revision: 09 November 2023

Article published online:
06 June 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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