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Antineutrophil properties of natural gingerols in models of lupus
Ramadan A. Ali, Alex A. Gandhi, Lipeng Dai, Julia Weiner, Shanea K. Estes, Srilakshmi Yalavarthi, Kelsey Gockman, Duxin Sun, Jason S. Knight
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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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 3

6-Gingerol blocks PDE activity and raises cAMP levels.

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6-Gingerol blocks PDE activity and raises cAMP levels.
Human neutrophils...
Human neutrophils were treated with 6-gingerol. Some samples were additionally treated with forskolin, cAMP, and synthetic PDE4 inhibitors (rolipram and IBMX) as indicated. PDE activity (A), cAMP levels (B), and PKA activity (C and D) were measured with kits as described in Methods. In E, neutrophils were treated with APS IgG in the presence or absence of 6-gingerol and/or PKA inhibitor. NETosis was quantified by measuring the enzymatic activity of nuclease-liberated myeloperoxidase (MPO). Mean and SEM are presented for n = 3–4 independent experiments; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 by 1-way ANOVA corrected with Dunnett’s test.

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