research high-lights


Rice Bran Extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer’s disease

Mitochondrial dysfunction plays an important role in brain aging and has emerged to be an early event in Alzheimer’s disease (AD), contributing to neurodegeneration and the loss of physical abilities seen in patients suffering from this disease. We examined mitochondrial dysfunction in a cell culture model of Alzheimer’s disease (PC12APPsw cells) releasing very low β-amyloid (Aβ40) levels and thus mimicking early AD stages.  Our data show that these cells have impaired energy metabolism, low ATP levels and decreased endogenous mitochondrial respiration. Furthermore, protein levels of PGC1α as well as of Mitofusin 1 were decreased. PC12APPsw cells also showed an increased mitochondrial content, probably due to an attempt to compensate the impaired mitochondrial function. Recent data showed that stabilized rice bran extract (RBE) protects from mitochondrial dysfunction in vivo (doi: 10.1016/j.phrs.2013.06.008). To assess the effect of a RBE on mitochondrial function, we treated PC12APPsw cells for 24h with RBE. Key components of RBE are oryzanols, tocopherols and tocotrienols, all substances that have been found to exert beneficial effects on mitochondrial function. RBE incubation elevated ATP production, respiratory rates as well as PGC1α protein levels in PC12APPsw cells, thus improving the impaired mitochondrial function assessed in our cell culture AD model. Therefore, RBE represents to be a promising nutraceutical for the prevention of Alzheimer’s disease.

Hagl S, Grewal R, Ciobanu I, Helal A, Khayyal MT, Muller WE, Eckert GP
Rice Bran Extract compensates mitochondrial dysfunction in a cellular model of early Alzheimer's disease
Journal of Alzheimer`s Disease (JAD) 2014, accepted


Omega-3 Polyunsaturated Fatty Acids improve mitochondrial dysfunction in brain aging

The present study investigated the effects of orally administered long chain omega-3 polyunsaturated fatty acids (PUFA) on mitochondrial function and processing of the amyloid precursor protein (APP) in brains of young (3 months old) and aged (24 months old) NMRI-mice. Neuroprotective properties of fish oil (FO) (1,7 ml/kg p.o) were assessed ex vivo after 21 days in dissociated brain cells (DBC) and isolated mitochondria. Docosahexaenoic acid (DHA) levels were significantly lower in blood and brains of aged mice which was compensated by FO administration. Isolated DBC and mitochondria from aged mice showed significantly lower adenosine triphosphate (ATP) levels and reduced activity of complex I+II and IV of the mitochondrial respiration system, respectively. FO restored the age-related decrease in respiration and improved ATP production. Moreover, FO increased the levels of the anti-apoptotic Bcl-2 protein. Cell membrane fractions isolated from the brain of aged mice exhibited lower membrane fluidity, which was partially improved under FO treatment. In comparison to young animals, levels of neuroprotective sAPPα were significantly lower in the brain of aged mice.  However, levels of sAPPα, Aβ and C-terminal APP fragments (CTF) were largely unchanged after FO treatment in aged mice. Neuroprotectin D-1 (NPD-1) represents a neuroprotective compound that is derived from unesterified DHA. Levels of NPD1-like metabolites (NPD1-like) and of unesterified DHA were significantly increased in brains of aged mice. FO treatment further strongly increased NPD1-like levels indicating an accelerated conversion rate of free DHA to NPD1-like. Our findings provide new mechanisms underlying the neuroprotective actions of omega-3 PUFA and identified FO as promising nutraceutical to delay age-related mitochondrial dysfunction in the brain.

Afshordel S, Hagl S, Werner D, Rohner N, Kogel D, Bazan N, Eckert GP.
Omega-3 Polyunsaturated Fatty Acids improve mitochondrial dysfunction in brain aging - impact of Bcl-2 and NPD-1
Prostaglandins Leukot Essent Fatty Acids 2014, in press



Rice bran extract protects from mitochondrial dysfunction in guinea pig brains

Mitochondrial dysfunction plays a major role in the development of age-related neurodegenerative diseases and recent evidence suggests that food ingredients can improve mitochondrial function. In the current study we investigated the effects of feeding a stabilized rice bran extract (RBE) on mitochondrial function in the brain of guinea pigs. Key components of the rice bran are oryzanols, tocopherols and tocotrienols, which are supposed to have beneficial effects on mitochondrial function. Concentrations of α-tocotrienol but not γ-tocotrienol were significantly elevated in brains of RBE fed animals and thus may have provided protective properties. Overall respiration and mitochondrial coupling were significantly enhanced, which suggests improved mitochondrial function in brains of RBE fed animals. Cells isolated from brains of RBE fed animals showed significantly higher MMP and ATP levels after sodium nitroprusside (SNP) challenge indicating resistance against mitochondrial dysfunction. Experimental evidence indicated increased mitochondrial mass in guinea pig brains, such as enhanced citrate synthase activity, increased cardiolipin as well as respiratory chain complex I and II and TIMM levels. In addition levels of Drp1 and fis1 were also increased in brains of guinea pigs fed RBE, indicating enhanced fission events. Thus, RBE represents a potential nutraceutical for the prevention of mitochondrial dysfunction and oxidative stress in brain aging and neurodegenerative diseases.

Hagl S, Alexa Kocher A, Christina Schiborr C, Eckert S, Ciobanu I, Birringer M, Al-Askary H, Amr Helal A, Khayyal MT, Frank J, Muller WE, Eckert GP
Rice bran extract protects from mitochondrial dysfunction in guinea pig brains
Pharmacol Res. 2013, 76C:17-27

© Prof. Dr. Gunter P. Eckert 2018