Ginger intake suppresses neutrophil extracellular trap formation in autoimmune mice and healthy humans

Abstract

We previously reported that treatment of mice with 6-gingerol, the most abundant phytochemical in ginger root, leads to phosphodiesterase inhibition that counteracts neutrophil hyperactivity in models of antiphospholipid syndrome (APS) and lupus. Here, we explored the extent to which oral intake of a whole-ginger extract would similarly impact neutrophils in both autoimmune mice and healthy humans. In vitro, a solubilized ginger extract was able to attenuate neutrophil extracellular trap formation (NETosis) by human neutrophils through a mechanism that was dependent upon the cyclic AMP–dependent kinase, protein kinase A. When mice with features of either APS or lupus were administered a ginger extract orally, they demonstrated reduced circulating NETs, as well as the tempering of other disease outcomes, such as large-vein thrombosis (APS) and autoantibody production (lupus). In a pilot clinical trial, which was validated in a second cohort, daily intake of a ginger supplement for 7 days by healthy volunteers boosted neutrophil cAMP, inhibited NETosis in response to disease-relevant stimuli, and reduced circulating plasma NET levels. In summary, this work demonstrates that ginger intake restrains neutrophil hyperactivity in autoimmune mouse models and that ginger consumption by healthy individuals makes their neutrophils more resistant to NETosis.

Communications between Neutrophil–Endothelial Interaction in Immune Defense against Bacterial Infection

“…The kringles 1-3 and its kringle 4 directly interact with leukocyte beta1and beta2-integrins [77] herbimycin A Inhibits of beta2 integrin-mediated tyrosine signaling [78] Inhibit NET formation C34 Inhibits TLR4 [82] 6-gingerol Inhibits phosphodiesterase [83] nNIF and NRPs Blocks NET formation in vitro and in mouse models of infection and systemic inflammation…”

“…For instance, PAD4 inhibitors such as Cl-amidine or GSK484 can inhibit NET formation to decrease the NET-mediated inflammation [ 79 , 80 , 81 , 82 ]. The phosphodiesterase inhibition of 6-gingerol shows the NET inhibition as well [ 83 ]. Reports show that nNIF and NRPs reduce inflammation by blocking NET formation in vitro and in mouse models of infection, and blocking systemic inflammation [ 84 ].…”