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Antineutrophil properties of natural gingerols in models of lupus
Ramadan A. Ali, … , Duxin Sun, Jason S. Knight
Ramadan A. Ali, … , Duxin Sun, Jason S. Knight
Published December 29, 2020
Citation Information: JCI Insight. 2021;6(3):e138385. https://doi.org/10.1172/jci.insight.138385.
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Research Article Inflammation

Antineutrophil properties of natural gingerols in models of lupus

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Abstract

Ginger is known to have antiinflammatory and antioxidative effects and has traditionally been used as an herbal supplement in the treatment of various chronic diseases. Here, we report antineutrophil properties of 6-gingerol, the most abundant bioactive compound of ginger root, in models of lupus and antiphospholipid syndrome (APS). Specifically, we demonstrate that 6-gingerol attenuates neutrophil extracellular trap (NET) release in response to lupus- and APS-relevant stimuli through a mechanism that is at least partially dependent on inhibition of phosphodiesterases. At the same time, administration of 6-gingerol to mice reduces NET release in various models of lupus and APS, while also improving other disease-relevant endpoints, such as autoantibody formation and large-vein thrombosis. In summary, this study is the first to our knowledge to demonstrate a protective role for ginger-derived compounds in the context of lupus. Importantly, it provides a potential mechanism for these effects via phosphodiesterase inhibition and attenuation of neutrophil hyperactivity.

Authors

Ramadan A. Ali, Alex A. Gandhi, Lipeng Dai, Julia Weiner, Shanea K. Estes, Srilakshmi Yalavarthi, Kelsey Gockman, Duxin Sun, Jason S. Knight

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Figure 7

The synthetic PDE4 inhibitor rolipram suppresses APS-mediated NETosis and venous thrombosis.

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The synthetic PDE4 inhibitor rolipram suppresses APS-mediated NETosis an...
Human neutrophils were stimulated with APS IgG for 3 hours. Some samples were additionally treated with the PDE4 inhibitor rolipram. NETosis was quantified by measuring the enzymatic activity of nuclease-liberated myeloperoxidase (MPO) (A). MPO-DNA complexes were assessed for control IgG- or APS IgG-treated mice in the presence or absence of rolipram (B). Thrombus formation was assessed at 24 hours. Thrombus length (C) and thrombus weight (D) were measured; **P < 0.01, ***P < 0.001, ****P < 0.0001 by 1-way ANOVA corrected with Dunnett’s test.

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