The effects of two highly bioavailable curcumin preparations on the activation of glial cells and chronic neuroinflammation in GFAP-IL6 mice

Abstract

Neuroinflammation is a pathophysiological process present in a number of neurodegenerative disorders, including following acute insults such as stroke, traumatic brain injury including chronic traumatic encephalopathy as well as age-related CNS disorders such as Huntington's disease, Parkinson's disease and Alzheimer's disease (AD). Although there is still much debate over the initial trigger for these neurodegenerative disorders, neuroinflammation appears to be a major contributor, and therefore anti-inflammatory drugs including cytokine suppressive anti-inflammatory drugs (CSAIDs) might be promising therapeutic options to limit neuroinflammation, neurodegeneration and therefore improve the clinical outcome. One of the most promising CSAIDs is curcumin, which modulates the activity of several transcription factors (e.g., STAT, NF-IºB, AP-1), most likely by interfering with upstream pro-inflammatory signaling pathways. Curcumin is a potent CSAID, but is not soluble in water and oily solvents like other polyphenols but soluble in methanol and ethanol, and degrades at low PH, it has low solubility and bioavailability in vivo. In order to increase its bioavailability, a variety of curcumin preparations have been designed, which lead to increased bioavailability, with the goal to achieve therapeutic concentrations in the brain. The aim of this thesis was to investigate the effect of two different formulations of curcumin, Meriva curcumin phytosome (MCP) and Longvida curcumin (LC) in GFAP-IL6 mice, a model of chronic microglial activation. MCP preparations were fed for short term (one month) in three doses (140mg/kg bw, 70mg/kg bw and 35mg/kg bw whereas LC was fed long term (6 months) at a dose of 500ppm. This study has investigated that, the MCP at a reasonable dose (highest dose: 140mg/kg bw, approx. 12mg/kg bw in humans) and LC (500ppm~60mg/kg bw, approx. 5.5mg/kg bw in humans) is able to significantly downregulate the microglial and astroglial activation in the GFAP-IL6 measured by various anatomical markers. It also has investigated that both formulations of curcumin have the potential to reverse the activation of microglial and astrocytes measured through morphological tools. Altogether this study did both answered some questions and opened a new window of possibilities in order to ameliorate the chronic neuroinflammation symptoms caused by over-activation of microglia and astrocytes in the brain.

Date of Award	2019
Original language	English