In a new clinical trial, scientists from the University of Michigan, Ann Arbor and the University of Colorado School of Medicine found that oral administration of ginger modulates neutrophils (type of white blood cell) and neutrophil extracellular trap (NET) formation, also known as NETosis, in autoimmune mouse models and healthy humans. This is important because NETs are microscopic spider web-like structures that propel inflammation and clotting, which contribute to many autoimmune diseases, including lupus, antiphospholipid syndrome and rheumatoid arthritis.
Ali et al. explored the extent to which oral intake of a whole-ginger extract would similarly impact neutrophils in both autoimmune mice and healthy humans. Image credit: Siala.
Chronic, incurable autoimmune diseases such as antiphospholipid syndrome (APS) and lupus are associated with significant morbidity, mortality, and health care costs.
Lupus is the prototypical systemic autoimmune disease characterized by autoantibodies against nuclear components, which result in circulating immune complexes that deposit in and damage organs.
APS, sometimes presenting in patients with lupus and sometimes as a standalone autoimmune disease, is associated with aberrant innate immune and vascular cell activation resulting in a markedly increased risk of thrombosis in vascular beds of all sizes.
While these diseases demonstrate unique clinical phenotypes, there is convincing evidence that both are pathologically driven by a shared mechanism: dysfunctional and exaggerated NET formation (termed NETosis).
Through NETosis, neutrophils expel their nuclear chromatin in pro-inflammatory web-like structures that are decorated with potentially toxic granule-derived proteins.
Excessive NETosis propels inflammatory and thrombotic cascades, contributing to end organ damage over time and to the pathophysiology of many autoimmune diseases, including APS and lupus.
“There are a lot of diseases where neutrophils are abnormally overactive,” said Dr. Kristen Demoruelle, senior co-author of the study.
“We found that ginger can help to restrain NETosis, and this is important because it is a natural supplement that may be helpful to treat inflammation and symptoms for people with several different autoimmune diseases.”
In the clinical trial, the researchers found that daily intake of a ginger supplement for seven days (20 mg of gingerols/day) by healthy volunteers boosted a chemical inside the neutrophil called cAMP.
These high levels of cAMP then inhibited NETosis in response to various disease-relevant stimuli.
“Our research, for the first time, provides evidence for the biological mechanism that underlies ginger’s apparent anti-inflammatory properties in people,” said Dr. Jason Knight, senior co-author of the study.
“There are not a lot of natural supplements, or prescription medications for that matter, that are known to fight overactive neutrophils.”
“We, therefore, think ginger may have a real ability to complement treatment programs that are already underway.”
“The goal is to be more strategic and personalized in terms of helping to relieve people’s symptoms.”
The findings were published in the journal JCI Insight.
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Ramadan A. Ali et al. 2023. Ginger intake suppresses neutrophil extracellular trap formation in autoimmune mice and healthy humans. JCI Insight 8 (18): e172011; doi: 10.1172/jci.insight.172011
