Effect of a Canton herbal tea on the toxicity of amyloid-beta peptide in cell culture and a transgenic mouse model of Alzheimer's disease

Abstract

Alzheimer’s disease (AD) is the main cause of dementia and is a high prevalence neurodegenerative disease for people aged 65-year-old or above. Problems arise from aging are making AD a high economic burden to the families and society.

Cognitive decline and decrease in learning and memory are the classical diagnostic symptoms of AD. Recent research highlights retinal changes in function and structure as early diagnostic markers in AD. Amyloid-beta (Aβ) peptide is considered one of the main factors that contribute to the AD progression. Recently, US FDA approved Aducanumab is known to reduce Aβ accumulation and China’s NMPA approved Sodium Oligomannate is known to regulate microbiota dysbiosis. However, the effectiveness of these AD drugs is still controversial. Immune modulation during the progression of AD specifically aiming at microglia in the central nerve system worth more investigation.

Canton herbal tea (CHT) is a traditional Chinese herbal drink well-known in south China with the “ameliorating fire” effect. Wanglaoji (WLJ) CHT is one of the most famous and popular daily drink in south China. It has been reported to improve immune reaction under stress in mice and anti-Aβ1-42 toxicity effect in Caenorhabditis elegans model. Active compounds of the WLJ CHT such as caffeic acid and chlorogenic acid were reported to reduce oxidative stress in mice. Here, I would like to investigate whether this CHT has the effect of improving cognitive and retinal function via immune modulation both in vivo and in vitro.

The 5xFAD transgenic mouse model without Pde6brd1 mutation was used in this study. 12- and 6-month-old 5xFAD mice were chosen to assess WLJ CHT therapeutic and protective effects respectively. After 2 months daily oral gavage, the mice were tested on cognitive function through various behavior tests (Morris water maze tests, open field tests, novel object recognition tests) and retinal function using electroretinography. Glial reaction and neuronal synaptic changes in retinal sections were compared among CHT fed, water fed 5xFAD mice and age-matched littermate control mice. CHT prophylactic effects before the challenge of oligomeric Aβ on the primary brain and retinal microglial cells were tested.

There was limited protective effect on spatial learning and retinal functions when the CHT treatment started at the age of 12 months. After 2 months 0.548 g/kg BW (HD) CHT feeding, only the spatial memory improved. When the oral feeding started at 6 months, 0.177 g/kg BW low dose (LD) CHT feeding improved the spatial learning ability of the 5xFAD mice. LD and HD CHT feeding showed protective effects on retinal functions. Enhanced synaptophysin expression and suppressed microglial activation in the retina were detected. However, in vitro experiments showed no significant anti-inflammation effect by WLJ CHT.

In conclusion, WLJ CHT had protective effect on the cognitive and retinal function at the early stage of AD in the 5xFAD mice. It inhibited retinal microglial activation and enhanced neuronal synaptophysin expression in the retina of 5xFAD mice.