Evaluation of Phytosomal Curcumin as an Anti-inflammatory Agent for Chronic Glial Activation in the GFAP-IL6 Mouse Model.

Faheem Ullah,Erika Gyengesi,Garry Niedermayer,Huazheng Liang,Gerald Münch

doi:10.3389/fnins.2020.00170

Faheem Ullah, Erika Gyengesi + Show 3 more

Open Access

https://doi.org/10.3389/fnins.2020.00170

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Abstract

Chronic glial activation is characterized by an increased number of activated microglia and astroglia; these secrete free radicals and cytotoxic cytokines, subsequently causing neuronal damage. This study investigated the hypothesis that a soy-lecithin based phytosomal curcumin formulation can decrease glial activation in the brains of GFAP-IL6 mice, a model of chronic glial activation, which exhibits gliosis in various regions of the brain. Three doses of Meriva curcumin (MC) (874, 436, and 218 PPM) were fed to 3-month-old GFAP-IL6 and wild-type (WT) mice for 4 weeks. As markers of glial activation, the total numbers of Iba-1+ and TSPO+ microglia and macrophages, and GFAP+ astrocytes, were determined in the cerebellum and hippocampus by immunohistochemistry and unbiased stereology. Furthermore, the morphology of the glial cells was assessed by confocal microscopy and Sholl analysis. Administration of phytosomal curcumin led to a dose-dependent reduction in neuroinflammatory markers. Phytosomal curcumin (874 PPM) decreased the number of microglia by 26.2% in the hippocampus and by 48% in the cerebellum of the GFAP-IL6 mice compared with the GFAP-IL6 mice on normal food. Additionally, GFAP+ astrocyte numbers in the hippocampus of the GFAP-IL6 mice were decreased by 42%. The GFAP-IL6 mice exhibited a different microglial morphology to the WT mice, showing an increased soma size and perimeter. This difference was significantly reduced by the 874 PPM phytosomal curcumin dose. Our findings demonstrate that phytosomal curcumin is able to attenuate the inflammatory pathology, and potentially reverse the detrimental effects of chronic glial activation.

Highlights

Neuroinflammation is a defense response of the central nervous system (CNS) to injury, infection, or the presence of toxic metabolites
Animals were randomly assigned to five groups: wild type (WT) C57BL/6 mice fed with control food pellets, glial fibrillary acidic protein (GFAP)-IL6 mice fed with control food pellets and three groups of GFAP-IL6 mice fed with food pellets containing 874, 436, and 218 PPM of Meriva curcumin (MC) (Table 1 and Supplementary Table S1)
Immunohistochemistry and stereological counting of Iba-1+ microglia were performed in the hippocampus and cerebellum of GFAP-IL6 mice fed with normal food or increasing doses of MC

Summary

Introduction

Neuroinflammation is a defense response of the central nervous system (CNS) to injury, infection, or the presence of toxic metabolites. Microglia are the key neuroinflammatory cells as they are activated in response to brain inflammation and release the ROS and cytokines that cause neurotoxicity (Beggs and Salter, 2007; Block et al, 2007). TSPO is a translocator protein expressed in the nervous system, on the outer mitochondrial membrane (Chen and Guilarte, 2008). It is predominantly expressed in the microglia, astrocytes, and macrophages in the blood vessels (Kuhlmann and Guilarte, 2000; Wilms et al, 2003). Previous studies conducted on GFAP-IL6 mice have shown a larger number of GFAP+ astrocytes in both the cerebellum and cortical areas compared with wild type (WT) mice (Chiang et al, 1994)

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