The protective effects of CSP in ischemic stroke models are associated with attenuation of IL-17/NF-κB-related neuroinflammation.
Bioinformatic analysis of public human ischemic stroke transcriptomic datasets showed enrichment of IL-17 and NF-κB signaling pathways.
In a public mouse MCAO single-cell RNA-seq dataset, microglia showed the largest MCAO-associated increase in IL-17/NF-κB-related module scores.
IL-17RA knockdown improved the viability of OGD-exposed SH-SY5Y cells.
CSP improved neurological and behavioral outcomes and increased cerebral blood flow in MCAO rats.
CSP reduced cerebral edema, infarct volume, and neuronal loss in MCAO rats.
CSP reduced microglial responses and IL-17A/IL-17RA expression in MCAO rat brain.
In OGD-exposed BV-2 microglial cells, CSP reduced IL-17A, IL-17RA, ACT1, TRAF6, IL-1β, IL-6, and the phosphorylated p65/total p65 ratio.
The authors conclude that CSP's protective effects are associated with attenuation of IL-17/NF-κB-related neuroinflammation, an association rather than demonstrated causation.
This study looked at whether polysaccharides from Cordyceps, a medicinal fungus, might protect the brain after an ischemic stroke (caused by blocked blood flow) and whether inflammation signaling involving IL-17 and NF-κB plays a role. Using public gene-activity data from human stroke patients and from mouse stroke models, the researchers found that IL-17 and NF-κB pathways were active in stroke, and that microglia, the brain's immune cells, showed the biggest increase in this activity. In lab experiments, reducing the IL-17 receptor (IL-17RA) in nerve-like cells improved their survival when deprived of oxygen and glucose. In rats with experimental stroke, Cordyceps polysaccharides improved neurological and behavioral outcomes, increased blood flow in the brain, and reduced brain swelling, tissue damage, nerve cell loss, microglial activation, and IL-17A/IL-17RA levels. In microglial cells exposed to oxygen-glucose deprivation, the treatment lowered IL-17 pathway proteins and inflammatory molecules. This research suggests that Cordyceps polysaccharides may reduce stroke-related brain injury partly by dampening IL-17/NF-κB inflammation. However, the work was done in cells and rats, and the link is described as an association, so it does not show that the treatment would work in people.
Wang H, Chen Y, Jiang Y, Liao Y, Xi S, Li X, et al.. (2026). Cordyceps Polysaccharides Attenuate Experimental Ischemic Stroke Injury: Association with IL-17/NF-κB Signaling.. International journal of molecular sciences. https://doi.org/10.3390/ijms27209035