Prevents and improves Alzheimer's disease
The main hypothesis of the brains of Alzheimer's disease patients is the accumulation of senile plaques around thenerve cells. The main component of these plaques is apeptide called amyloid β-peptide (Aβ), which is composed of 39 to 43 amino acids. Aβ is derived from the integral membrane amyloid precursor protein (APP) by proteolytic cleavage of β- and γ-secretase. A large Aβ production causes Aβ aggregation and eventually leads to the formation of senile plaques. Oxidative stress and inflammatory response have been proven to be the important damage induced by Aβ deposition in the brains of AD patients. In vivo oxidation and free radicals would cause the formation of Aβ fibrils, and further, Aβ-fibril-induced oxidative stress and inflammatory response would occur and result in the formation of more Aβ fibrils. The risk factor Aβ and high levels of nitric oxide (NO), reactive oxygen species (ROS), and free radicals would be accumulated repetitiously and lead to more serious AD pathogenesis. In addition, the Aβ oligomers act on synapses and further activate glial cells and astrocytes, eventually leading to progressive synapse and nerve damage. They then disrupt neuronal ion homeostasis, cause oxidative damage, and alter the activities of kinases and phosphatases, leading to neurofibrillary tangles. This then causes a deficiency of neurotransmitters, general loss of neural functions, and death of neural cells, which all eventually lead to the development of Alzheimer's disease.
Inhibition of Aβ-induced neurocytotoxicity through the cooperative mechanism of anti-oxidation and anti-oxidative inflammation
An important mechanism of red mold fermented product in preventing Alzheimer's disease is its anti-oxidative and anti-inflammatory abilities. Our study published in Applied Microbiology and Biotechnology indicates that Aβ40 treatments cause PC12 cell death, and alcohol extracts of red mold fermented product showed the ability to inhibit Aβ40 cytotoxicity. In the study, the ethanol extracts of M. purpureus NTU 568-fermented product can significantly repress the expression of iNOS, an Aβ40-induced inflammatory factor, reduce the production of NO and ROS, and can also cause the reduction of oxidative stress.
Improving memory and learning abilities in animal models with Alzheimer's disease by inhibiting Aβ depositions in the brain
Rats infused with Aβ40 to induce Alzheimer's disease were used in our study as animal models. After 28 days of continuous Aβ40 infusions into the left cerebral ventricles, the infused rats displayed a significant deficit in memory and learning abilities compared to those infused with vehicle solutions. Furthermore, the acetylcholinesterase activity, oxidization level, and inflammatory responses were also significantly increased in Aβ40-infused rats. In the passive avoidance test, AD rats fed with NTU 568 fermented product stayed in a bright room for a significantly longer period compared to untreated AD rats. With regard to the influence on memory, the time spent finding a platform in the watermaze test was significantly reduced in AD rats that were fed NTU 568 fermented product compared to untreated AD rats. The above proves that NTU 568 fermented product actually ameliorates the impairment of memory and learning ability of AD rat models. AD rats fed red mold fermented product demonstrate memory and learning results that resemble those shown in rats exhibiting normal memory abilities and require less searching time compared to untreated AD rats in tests performed.
NTU 568 fermented product can significantly repress the acetylcholinesterase activity that is increased by the influence of Aβ. Severe oxidative stress and inflammatory responses to the cerebral cortex and hippocampus were revealed in AD rat models with impairment of memory and learning abilities. Furthermore, the Aβ-induced oxidative stress and inflammatory response are proved to result in more severe formation and deposition of Aβ fibrils in the brain. The malignant cycle would cause more and more Aβ accumulation, oxidative stress, and inflammatory response to damage the brain and memory. However, these impairments can be ameliorated by the daily feeding of NTU 568 fermented product, and the effects of Aβ40 accumulation can be significantly reduced eventually. It has been inferred that NTU 568 fermented product is able to reduce Aβ40 accumulation in the hippocampus because of its ability to inhibit oxidative stress and inflammatory responses. As the oxidative and inflammatory factors fail to promote the accumulation of Aβ40 infused into the brain, Aβ40 is unable to cause impairments to the brain, and thus, the memory and learning abilities become ameliorated.
