Curcugreen Treatment Prevented Splenomegaly and Other Peripheral Organ Abnormalities in 3xTg and 5xFAD Mouse Models of Alzheimer's Disease.

Jayeeta Manna,Panchanan Maiti,Gary L Dunbar

doi:10.3390/antiox10060899

Abstract

Metabolic dysfunction and immune disorders are common in Alzheimer’s disease (AD). The mechanistic details of these epiphenomena in AD are unclear. Here, we have investigated whether a highly bioavailable curcuminoid formulation, curcugreen (CGR), can prevent abnormalities in peripheral organs of two mouse models of AD. Eighteen- and 24-month-old male and female 3xTg and 5xFAD mice were treated with CGR (100 mg/kg) for 2 months, orally. Cytoarchitectural changes of spleen, liver, kidney and lungs were studied by H&E stain. Apoptotic death was confirmed by TUNEL staining. Amyloid deposition, pTau levels, proinflammatory, anti-inflammatory and cell death/survival markers were studied by Western blots. Curcugreen reduced the observed splenomegaly (3xTg) and degeneration of spleen, granulomatous inflammation in the kidney, hepatic sinusoidal disorganization, hepatocellular hypertrophy, inflammation of the central hepatic vein, infiltration and swelling of lung tissues, and apoptotic death in all these areas in both 3xTg and 5xFAD mice. Similarly, CGR decreased amyloid deposition, pTau, proinflammatory markers, cell loss and decrements in anti-inflammatory markers in both 3xTg and 5xFAD mice. Peripheral organ abnormalities and inflammatory responses in AD were ameliorated by curcuminoid treatment.

Highlights

Metabolic activities in the liver, kidneys and other accessory peripheral organs determine the state of physiological outcomes and maintain cardiovascular efficiency, whereas, decreased efficiency of peripheral organs leads to metabolic dysfunction which has a strong association with vascular injury and dementia [1,5]
We found a decrease in phosphorylated tau (pTau) levels by CGR treatment in 3xTg mice (Figure 11), suggesting curcuminoids inhibited either pTau formation or might degrade their levels through other mechanisms, such as the proteasomal system
Curcugreen is bioavailable to most of the peripheral organs and micromolar levels of it can protect against degenerative changes in liver, kidney, spleen and lungs of 3xTg and

Summary

Introduction

Metabolic activities in the liver, kidneys and other accessory peripheral organs determine the state of physiological outcomes and maintain cardiovascular efficiency, whereas, decreased efficiency of peripheral organs leads to metabolic dysfunction which has a strong association with vascular injury and dementia [1,5]. Recent clinical studies have indicated that several metabolic disorders, such as diabetes, hypertension, obesity, dyslipidemia, and insulin resistance are the risk factors for AD, which are directly, or indirectly, associated with the impairment of energy metabolism, increased inflammation, and insulin resistance [6,7]. Recent evidence suggests that metabolic dysfunction of the liver, including significantly increased ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) levels, are associated with mild-cognitive impairment (MCI), AD, and other neurodegenerative changes [8].

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