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Iso-α-acids, bitter components of beer, prevent inflammation and cognitive decline induced in a mouse model of Alzheimer′s disease

Peroxisome Proliferator-Activated Receptor (PPAR-γ) has been known to be a therapeutic target in several disease states including diabetes, arterial sclerosis, inflammatory and in tumor states. Recently, its role as a potential therapeutic target in Alzheimer's disease (AD) has been considered. PPAR-γ can suppress inflammation and enhance microglial phagocytosis, among other known functions. In light of an increased growth rate among aging population and the need to prevent and treat age-related memory decline and dementia, Ano Y et al, 2017 have studied the effects of PPAR-γ in suppressing memory decline and inflammation in a mouse model of Alzheimer's disease (AD). In particular, they studied the effects of Iso α-acids (bitter components of beer) in reducing effects of dementia and AD-like pathology in a mouse model of AD. Via oral administration of iso-α-acids in normal and AD mouse the authors studied the role of iso-α-acids as possible PPAR-γ agonists in the microglial phagocytosis of amyloid (Aβ) in mouse brain.

Microglial phagocytosis of 6-carboxyfluorescein-labeled Aβ1-42 (Aβ-FAM, AnaSpec, Fremont, CA) was evaluated following microglial cells isolation from newborn mice, plating and incubation with 500 nM Aβ-FAM for 24 hours after sample treatment for 12 hours. The extracellular Aβ-FAM was then quenched with 0.2% trypan blue, pH 4.4 and the cellular fluorescence intensity was measured at 485 nm excitation/535 nm emission. A PPAR-γ antagonist was also used in some experiments for comparison.

The results showed that iso-α-acids compounds (all six stereo-isomers) enhanced Aβ phagocytosis via activation of the receptor (PPAR-γ) (Figure) and promoted anti-inflammatory activity of primary cultured microglia. Furthermore, the authors were able to demonstrate that the effects of these compounds had a positive impact on reducing AD-like pathology (21% reduction in amyloid (Aβ) in the cortex) along with significant improvement in cognitive function via an object recognition test.

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