Aims: Chronic neuroinflammation is a hallmark of several neurodegenerative diseases, and uncovering the underlying mechanisms is crucial for developing effective therapies. Curcuminoids are well-known for their anti-inflammatory and neuroprotective properties. This study investigated the anti-inflammatory potential of a phytosomal curcumin (highly bioavailable formulation) in a mouse model of chronic neuroinflammation, overexpressing interleukin-6 under the control of the glial fibrillary acidic protein promoter (GFAP-IL6). 

Method: WT and homozygous GFAP-IL6 mice, both sexes, were fed with phytosomal curcumin enriched diet (2000 ppm) or control chow from 1-month old. Brains were collected for quantitative analysis of glia numbers and morphology, using stereology and 3D single cell reconstructions, and for transcriptomic analysis via RT-qPCR in brain regions involved in motor control, learning and memory.  Plasma curcuminoid levels were quantified with ultra-high pressure liquid chromatography-mass spectrometry (UPLC-MS) to assess bioavailability of curcumin formulation.  

Results: Immunostaining of microglia in GFAP-IL6 mice revealed a significant decreased of glia activation in the hippocampus and cerebellum. Curcumin supplementation demonstrated an interference with neuroinflammatory pathways by downregulating the mRNA levels of pro-inflammatory markers P2rx7 and Nfkb1 in the hippocampus as compared to controls. The concentration of curcumin in plasma of GFAP-IL6 (2268.71ng/ml) mice was slightly higher than those of the WT (2088.04ng/ml). 

Conclusion: The current study demonstrates a positive impact of phytosomal curcumin supplementation in homozygous GFAP-IL6 mice on neuroinflammatory markers and glial cells. This provides foundational evidence for the therapeutic potential of modified, highly bioavailable curcumin preparations as an anti-inflammatory agent against the detrimental effects of neuroinflammation.