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

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.

Tetrahydrocurcumin Has Similar Anti-Amyloid Properties as Curcumin: In Vitro Comparative Structure-Activity Studies

“…The same blot was also probed with anti-beta tubulin antibody for loading control. The relative optical density was measured using Image-J software (https://imagej.nih.gov/ij/ (accessed on 5 June 2021) [32][33][34].…”

“…To check the binding capabilities of different Cur-derivatives with amyloid plaques, 5× familial Alzheimer's disease (5× FAD) mice brain tissue and age-matched wild-type mice were used, as described previously [33,34]. Briefly, B6SJL-Tg mice (APPSwFlLon, 1136799Vas/J) which overexpressed human amyloid precursor protein (APP) with three mutations [Swedish (K670N, M671L), Florida (I716V) and London (V717I)] and two mutations on presenilin (PS) genes (PSEN1*M146L*L286V)] [7,8].…”

“…The standard housing conditions including temperature at 22 • C and ad libitum access of food and water with 12-h light/12-h dark, reverse-light cycle was maintained. The transgenic characteristics of 5× FAD mice were confirmed by genotyping using polymerase chain reaction (PCR) from the tail snip at the age of 3 weeks [33,34]. The Institutional Animal Care and Use Committee of the Saginaw Valley State University approved this study (IACUC no: 1513829-1 and 1645929-2).…”