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Article

Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides

1
Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University, Philosophenweg 14, 07743 Jena, Germany
2
Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen 518000, China
3
Department of Chemistry and Pharmacy, Pharmaceutical Technology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Cauerstrasse 4, 91058 Erlangen, Germany
*
Author to whom correspondence should be addressed.
Authors contributed equally to this work.
Biomolecules 2021, 11(5), 746; https://doi.org/10.3390/biom11050746
Submission received: 14 April 2021 / Revised: 6 May 2021 / Accepted: 10 May 2021 / Published: 17 May 2021
(This article belongs to the Collection Bioactive Lipids in Inflammation, Diabetes and Cancer)

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 chromatography-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. Importantly, 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 antirheumatic properties of TWG.
Keywords: Tripterygium wilfordii glycosides; lipoxygenase; cyclooxygenase; inflammation; specialized pro-resolving mediators Tripterygium wilfordii glycosides; lipoxygenase; cyclooxygenase; inflammation; specialized pro-resolving mediators

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MDPI and ACS Style

Zhang, K.; Pace, S.; Jordan, P.M.; Peltner, L.K.; Weber, A.; Fischer, D.; Hofstetter, R.K.; Chen, X.; Werz, O. Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides. Biomolecules 2021, 11, 746. https://doi.org/10.3390/biom11050746

AMA Style

Zhang K, Pace S, Jordan PM, Peltner LK, Weber A, Fischer D, Hofstetter RK, Chen X, Werz O. Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides. Biomolecules. 2021; 11(5):746. https://doi.org/10.3390/biom11050746

Chicago/Turabian Style

Zhang, Kehong, Simona Pace, Paul M. Jordan, Lukas K. Peltner, Alexander Weber, Dagmar Fischer, Robert K. Hofstetter, Xinchun Chen, and Oliver Werz. 2021. "Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides" Biomolecules 11, no. 5: 746. https://doi.org/10.3390/biom11050746

APA Style

Zhang, K., Pace, S., Jordan, P. M., Peltner, L. K., Weber, A., Fischer, D., Hofstetter, R. K., Chen, X., & Werz, O. (2021). Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides. Biomolecules, 11(5), 746. https://doi.org/10.3390/biom11050746

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