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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 1

Gingerol suppresses NETosis in response to various stimuli.

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Gingerol suppresses NETosis in response to various stimuli.
Human neutro...
Human neutrophils were isolated from healthy volunteers and then treated with various stimuli for 3 hours in the presence of different gingerol analogues. NETosis was quantified by measuring the enzymatic activity of nuclease-liberated myeloperoxidase (MPO). Dose response to LPS-mediated NETosis upon treatment with 6-gingerol (A), 8-gingerol (B), and 10-gingerol (C). NETosis in response to PMA (D), RNP ICs (E), and APS IgG (F) was quantified in the presence of 10 μM gingerol. NETosis was assessed by immunofluorescence microscopy (G). Neutrophils were treated with LPS, PMA, RNP ICs, or APS IgG in the presence or absence of 6-gingerol (10 μM). Blue, DNA; green, extracellular neutrophil elastase. Scale bar: 100 microns. For A–F, mean and SEM are presented for n = 3 independent experiments; *P < 0.05, **P < 0.01, ****P < 0.0001 as compared with the 0 μM gingerol group by 1-way ANOVA corrected with Dunnett’s test.

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