Effects of secondary plant metabolites and micronutrients on mitochondrial functions in a cellular model of early Alzheimer disease

Abstract

One advance that mankind has achieved over time as a result of medical and technical progress is increasing life expectancy. However, this is also accompanied by an increase in age-related diseases. One of these is Alzheimer's disease (AD), which is associated with the loss of physical and cognitive abilities as well as personality changes. To date, there is no cure for AD. Since symptoms do not appear until later in life, it is important to find a way to delay symptomatology as much as possible in advance and to take preventive or supportive measures. AD is characterized, among other things, by changes in three major areas, including mitochondrial dysfunction (MD) with a decrease in ATP and a change in the respiratory chain. Impaired amyloid-beta (Aβ) processing and alterations in glycolytic metabolism. It has been shown that physical activity, as well as nutrition, can prevent certain diseases, including AD. With this in mind, this work investigated the effects of hesperetin (HstP) from orange peel, magnesium orotate (MgOr) and folic acid, as well as the constituents caffeine, kahweol, and cafestol found in coffee, on the early symptoms of AD. Almost all compounds were shown to significantly increase ATP levels in the SH-SY5Y- APP695 cell model. Specifically, HstP was able to decrease the levels of reactive oxygen species. MgOr and Fol, in particular, altered Aβ-processing and lowered the levels. Coffee constituents affected glycolytic metabolism and led to an increase in aerobic glycolysis. Each of the groups of compounds acted on a different area of AD. To check whether a combination of all substances (cocktail) addressed all areas, this cocktail was also tested for its effect. It was found that ATP levels were increased and Aβ levels were decreased. There were no effects on any other areas. In summary, although there is no cure for AD, certain substances can positively influence the disease and have a preventive effect. This makes them promising agents that deserve further research.