S-allyl cysteine suppresses lipopolysaccharide-induced microglial inflammation accompanied by attenuation of JNK1/2 and STAT3 signaling

Background
S-allyl-L-cysteine (SAC) is a garlic-derived organosulfur compound with reported anti-inflammatory properties. SAC has been detected in the brain after oral administration in animal studies, suggesting relevance to neuroinflammatory processes; however, its direct effects on nutrient-responsive glial cells remain unclear. Previous human studies suggest that SAC-enriched garlic extracts alleviate subjective mental fatigue by modulating glial inflammation.

Objectives
The present study aimed to examine whether SAC directly modulates lipopolysaccharide (LPS; 1–100 ng/ml)-induced inflammatory responses in astrocyte (AWT) and microglial (MG6) cell lines.

Methods and results
LPS reduced cell viability in a concentration-dependent manner in both AWT and MG6 cells, inducing apoptotic cell death in AWT cells but not in MG6 cells. SAC at physiologically relevant concentrations did not prevent LPS-induced reduction in AWT cell viability, whereas it significantly attenuated the reduction in MG6 cell viability induced by LPS at 10 ng/ml. Using the Olink Target 48 Mouse Cytokine Panel, LPS markedly increased the secretion of eight inflammatory cytokines and chemokines, including CCL5, CXCL1, CXCL2, G-CSF, IL-1α, IL-1β, IL-6, and TNFα, in MG6 cells. Additionally, SAC significantly suppressed LPS-induced mRNA expression of these inflammatory mediators. SAC also attenuated LPS-induced phosphorylation of JNK1/2 and STAT3, while NF-κB phosphorylation was unaffected. Furthermore, JNK-IN-8, a selective JNK inhibitor, but not STAT3 knockdown by RNA interference, significantly suppressed the LPS-induced IL-1β protein expression.

Conclusion
These findings provide insight into the cellular mechanisms by which a dietary garlic-derived compound modulates microglial inflammatory responses and support a nutritional basis for the potential neuroprotective effects of SAC.