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Article

Anti-Inflammatory Extract from Soil Algae Chromochloris zofingiensis Targeting TNFR/NF-κB Signaling at Different Levels

1
Institute of Cell Biology, Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria
2
ADSI—Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, 6020 Innsbruck, Austria
3
Department of Biotechnology and Food Engineering, MCI—The Entrepreneurial School, 6020 Innsbruck, Austria
4
Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria
*
Authors to whom correspondence should be addressed.
Academic Editors: Johannes A. Schmid, Evangelos Kolettas, Kenneth B. Marcu and Alexander E. Kalyuzhny
Cells 2022, 11(9), 1407; https://doi.org/10.3390/cells11091407
Received: 21 February 2022 / Revised: 12 April 2022 / Accepted: 19 April 2022 / Published: 21 April 2022
Inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, are increasing in populations worldwide. The treatment of patients with AD and other forms of skin inflammation is mainly based on the use of topical corticosteroids or calcineurin inhibitors, which can cause significant side effects with long-term use. Therefore, there is a great need for the development of more effective and less toxic anti-inflammatory agents suitable for the treatment of chronic skin lesions. Here, we screened a number of strains from the ASIB 505 terrestrial algae collection and identified a green algae Chromochloris zofingiensis with pronounced anti-inflammatory properties. We found that a crude nonpolar extract of C. zofingiensis (ID name NAE_2022C), grown upon nitrogen deprivation, acts as a bioactive substance by inhibiting TNFR/NF-κB responses in human skin keratinocyte HaCaT cells. We also found that NAE_2022C suppressed the secretion of pro-inflammatory cytokine tumor necrosis factor α (TNFα) and several Th1- and Th2-related chemokines in a reconstituted human epidermis. The TNFR/NF-κB pathway analysis showed multiple inhibitory effects at different levels and disclosed a direct targeting of IKKβ by the extract. Bioassay-guided fractionation followed by high-resolution mass spectrometry detected diacylglyceryl-trimethylhomoserine (DGTS), Lyso-DGTS (LDGTS), 5-phenylvaleric acid, theophylline and oleamide as leading metabolites in the active fraction of NAE_2022C. Further analysis identified betaine lipid DGTS (32:0) as one of the active compounds responsible for the NAE_2022C-mediated NF-κB suppression. Overall, this study presents an approach for the isolation, screening, and identification of anti-inflammatory secondary metabolites produced by soil algae. View Full-Text
Keywords: Chromochloris zofingiensis; bioactive metabolites; anti-inflammatory effects; NF-κB; mass spectrometry Chromochloris zofingiensis; bioactive metabolites; anti-inflammatory effects; NF-κB; mass spectrometry
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MDPI and ACS Style

Leitner, P.D.; Jakschitz, T.; Gstir, R.; Stuppner, S.; Perkams, S.; Kruus, M.; Trockenbacher, A.; Griesbeck, C.; Bonn, G.K.; Huber, L.A.; Valovka, T. Anti-Inflammatory Extract from Soil Algae Chromochloris zofingiensis Targeting TNFR/NF-κB Signaling at Different Levels. Cells 2022, 11, 1407. https://doi.org/10.3390/cells11091407

AMA Style

Leitner PD, Jakschitz T, Gstir R, Stuppner S, Perkams S, Kruus M, Trockenbacher A, Griesbeck C, Bonn GK, Huber LA, Valovka T. Anti-Inflammatory Extract from Soil Algae Chromochloris zofingiensis Targeting TNFR/NF-κB Signaling at Different Levels. Cells. 2022; 11(9):1407. https://doi.org/10.3390/cells11091407

Chicago/Turabian Style

Leitner, Peter D., Thomas Jakschitz, Ronald Gstir, Stefan Stuppner, Sebastian Perkams, Maren Kruus, Alexander Trockenbacher, Christoph Griesbeck, Günther K. Bonn, Lukas A. Huber, and Taras Valovka. 2022. "Anti-Inflammatory Extract from Soil Algae Chromochloris zofingiensis Targeting TNFR/NF-κB Signaling at Different Levels" Cells 11, no. 9: 1407. https://doi.org/10.3390/cells11091407

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