In vivo evaluation of curcumin as an anti-inflammatory drug in a mouse model of chronic neuroinflammation

Abstract

The increased average life expectancy of the world population has resulted in a higher incidence and prevalence of chronic neurodegenerative diseases. Alzheimer's disease (AD) is the most commonly diagnosed dementia in humans. The typical cognitive and behavioral symptoms of the patients include changes in their personality, difficulties in daily life activities, deficits in language, speech, visuospatial skills, executive and memory functions. Abnormal aggregation of amyloid-I² and hyperphosphorylated tau protein is hallmark histopathological features in the brains of AD patients. An inflammatory reaction is commonly observed in the progression of AD which involves activated microglia, astrocytes and elevated levels of cytotoxic cytokines interleukin-1 (IL-1), IL-6 and TNF-I± in the patients' brains. Clinical evidence indicates a vicious cycle of the inflammatory process in different brain regions of AD patients by excessive release of various mediating factors and causing toxicity, injury to synapses and neurons. The role of IL-6 is particularly important in the AD process as clinical evidence shows a decline in cognitive functions of the patients by increased brain levels of this cytokine along with advancing age. GFAP-IL6 transgenic mouse model with overexpression of IL-6 in the brain is a suitable model to investigate structural and functional changes in the brain caused by IL-6 initiated inflammatory cascade. These mice exhibit significant phenotypic features similar to the human condition including brain inflammation, motor and cognitive impairment. Natural compounds with cytokine-suppressive anti-inflammatory activity could be protective against the neurological disease of the GFAP-IL6 mice. Curcumin is a plant-based natural compound with potent in vivo antioxidant, anti-inflammatory and cytokine-suppressive properties and no adverse effects are known by its long-term consumption. Long-term feeding of the GFAP-IL6 mice with the Longvida curcumin, high bioavailability nanoformulation of the compound could be protective against the development of their functional deficits and neurological disease. We aimed to investigate and compare ataxia phenotype, motor and memory performances of the GFAP-IL6 and WT mice and assess whether feeding with Longvida curcumin food could be preventive for neurological disease and functional impairment of the GFAP-IL6 mice.

Date of Award	2020
Original language	English