Beneficial modulation of lipid mediator biosynthesis in innate immune cells by antirheumatic tripterygium wilfordii glycosides

Zhang K, Pace S, Jordan PM, Peltner LK, Weber AC, Fischer D, Hofstetter RK, Chen X, Werz O (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Biomolecules MDPI

Book Volume: 11

Article Number: 746

Journal Issue: 5

DOI: 10.3390/biom11050746

Abstract

Tripterygium wilfordii glycosides (TWG) is a traditional Chinese medicine with effectiveness against rheumatoid arthritis (RA), supported by numerous clinical trials. Lipid mediators (LM) are biomolecules produced from polyunsaturated fatty acids mainly by cyclooxygenases (COX) and lipoxygenases (LOX) in complex networks which regulate inflammation and immune responses and are strongly linked to RA. The mechanism by which TWG affects LM networks in RA treatment remains elusive. Employing LM metabololipidomics using ultra-performance liquid chromatog-raphy-tandem mass spectrometry revealed striking modulation of LM pathways by TWG in human monocyte-derived macrophage (MDM) phenotypes. In inflammatory M1-MDM, TWG (30 µg/mL) potently suppressed agonist-induced formation of 5-LOX products which was confirmed in human PMNL and traced back to direct inhibition of 5-LOX (IC50 = 2.9 µg/mL). TWG also efficiently blocked thromboxane formation in M1-MDM without inhibiting other prostanoids and COX enzymes. Im-portantly, in anti-inflammatory M2-MDM, TWG (30 µg/mL) induced pronounced formation of specialized pro-resolving mediators (SPM) and related 12/15-LOX-derived SPM precursors, without COX and 5-LOX activation. During MDM polarization, TWG (1 µg/mL) decreased the capacity to generate pro-inflammatory 5-LOX and COX products, cytokines and markers for M1 phenotypes. Together, suppression of pro-inflammatory LM but SPM induction may contribute to the antirheu-matic properties of TWG.

Authors with CRIS profile

Alexander Christian Weber Lehrstuhl für Pharmazeutische Technologie und Biopharmazie Dagmar Fischer Lehrstuhl für Pharmazeutische Technologie und Biopharmazie

Involved external institutions

Friedrich-Schiller-Universität Jena DE Germany (DE) Shenzhen University (SZU) / 深圳大学 CN China (CN)

How to cite

APA:

Zhang, K., Pace, S., Jordan, P.M., Peltner, L.K., Weber, A.C., Fischer, D.,... Werz, O. (2021). Beneficial modulation of lipid mediator biosynthesis in innate immune cells by antirheumatic tripterygium wilfordii glycosides. Biomolecules, 11(5). https://doi.org/10.3390/biom11050746

MLA:

Zhang, Kehong, et al. "Beneficial modulation of lipid mediator biosynthesis in innate immune cells by antirheumatic tripterygium wilfordii glycosides." Biomolecules 11.5 (2021).

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