Red mold,diabetes, and oxidative stress: a review

Type 2 diabetes is a major health concern and a rapidly growing disease with a modern etiology, which produces significant morbidity and mortality. The optimal management of type 2 diabetes aims to control hyperglycemia, hypertension, and dyslipidemia to reduce overall risks. Diabetes and its complications usually develop as oxidative stress increases. Monascus-fermented rice, also called red mold rice or red mold dioscorea are used in China to enhance food color and flavor. Red mold-fermented products are popular health foods that are considered to have antiobesity, antifatigue, antioxidation, and cancer prevention effects. This review article describes the antidiabetic and antioxidative stress effects on humans and animals of red mold-fermented products or their secondary metabolites.     

Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions

Alzheimer's disease (AD) is a severe, chronic and progressive neurodegenerative disease associated with memory and cognition impairment ultimately leading to death. It is the commonest reason of dementia in elderly populations mostly affecting beyond the age of 65. The pathogenesis is indicated by accumulation of the amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT) in brain tissues and hyperphosphorylation of tau protein in neurons. The main cause is considered to be the formation of reactive oxygen species (ROS) due to oxidative stress. The current treatment provides only symptomatic relief by offering temporary palliative therapy which declines the rate of cognitive impairment associated with AD. Inhibition of the enzyme acetylcholinesterase (AChE) is considered as one of the major therapeutic strategies offering only symptomatic relief and moderate disease-modifying effect. Other non-cholinergic therapeutic approaches include antioxidant and vitamin therapy, stem cell therapy, hormonal therapy, use of antihypertensive or lipid-lowering medications and selective phosphodiesterase (PDE) inhibitors, inhibition of β-secretase and γ-secretase and Aβ aggregation, inhibition of tau hyperphosphorylation and intracellular NFT, use of nonsteroidal anti-inflammatory drugs (NSAIDs), transition metal chelators, insulin resistance drugs, etanercept, brain-derived neurotrophic factor (BDNF) etc. Medicinal plants have been reported for possible anti-AD activity in a number of preclinical and clinical trials. Ethnobotany, being popular in China and in the Far East and possibly less emphasized in Europe, plays a substantial role in the discovery of anti-AD agents from botanicals. Chinese Material Medica (CMM) involving Chinese medicinal plants has been used traditionally in China in the treatment of AD. Ayurveda has already provided numerous lead compounds in drug discovery and many of these are also undergoing clinical investigations. A number of medicinal plants either in their crude forms or as isolated compounds have exhibited to reduce the pathological features associated with AD. In this present review, an attempt has been made to elucidate the molecular mode of action of various plant extracts, phytochemicals and traditional herbal formulations investigated against AD as reported in various preclinical and clinical tests. Herbal synergism often found in polyherbal formulations were found effective to combat disease heterogeneity as found in complex pathogenesis of AD. Finally a note has been added to describe biotechnological improvement, genetic and genomic resources and mathematical and statistical techniques for empirical model building associated with anti-AD plant secondary metabolites and their source botanicals.     

Ascorbic acid, cognitive function, and Alzheimer's disease: a current review and future direction

This narrative review appraises the human and animal studies implicating ascorbic acid (AA) in normal cognitive function and Alzheimer's disease. A research framework for how nutrition affects brain aging is proposed with emphasis on AA intake, status, metabolism, and transport into brain tissue. A final synopsis highlights areas for future research regarding AA nourishment and healthy brain aging.     

Natural products and derivatives affecting neurotransmission relevant to Alzheimer's and Parkinson's disease

The two major neurodegenerative diseases Alzheimer's disease (AD) and Parkinson's disease (PD) are characterised by low levels in the brain of the neurotransmitters acetylcholine (ACh) and dopamine (DA), respectively. Clinical treatment of these two conditions is palliative and relies, in most cases, on improving stimulation at the relevant receptors by either increasing levels of the endogenous neurotransmitter or by the use of substances which have a similar agonist response. Natural products continue to provide useful drugs in their own right but also provide templates for the development of other compounds. The major advances in the treatment of AD have been the use of acetylcholinesterase inhibitors such as galantamine, huperzine A, physostigmine and its derivatives to increase the levels of ACh rather than the use of cholinergic compounds, although compounds with nicotinic properties have attracted some interest. In contrast, the treatment of PD has relied on the elevation of DA levels by use of L-DOPA, its precursor, and by the administration of dopaminergic agonists, especially the ergot alkaloid derivatives. The use of inhibitors of enzymes that cause breakdown of DA is an avenue which is being explored. As well as the major natural products of clinical interest, the paper discusses the chemistry, activity and usage of the constituents of plants used in traditional medicine for the treatment of diseases presenting symptoms similar to those characteristic for Alzheimer's or Parkinson's disease.     

Alois Alzheimer and Alzheimer's disease: a centennial perspective

The year 2006 is the centenary of the famous presentation of Alois Alzheimer which first described the neuropathology of Alzheimer's disease (AD). Since this presentation, enormous progress has been made in understanding the biology of AD. The central role of the beta-amyloid protein (Abeta) in the pathogenesis of AD and the relationship between plaque and tangle pathology is now much better understood. In this article, we review the current status of the amyloid hypothesis of AD and its role in the development of future therapy.     

Neuropeptides in Alzheimer's disease: a postmortem study

The concentration of 5 neuropeptides, neurotensin (NT), somatostatin (SRIF), corticotropin-releasing factor (CRF), bombesin and thyrotropin-releasing hormone (TRH) was measured in 3 cerebrocortical areas and several subcortical regions in post-mortem brains obtained from patients with histologically verified Alzheimer's disease and from controls without neurological or psychiatric disorders using sensitive and specific radioimmunoassay procedures. In Alzheimer's disease, reductions in the concentration of SRIF and CRF were observed in frontal and temporal cortex. In addition, in Alzheimer's disease, SRIF was also reduced in concentration in the hypothalamus, whereas CRF concentrations were reduced in the caudate nucleus. Neurotensin was reduced in concentration in the amygdala in Alzheimer's disease. No alterations in TRH or bombesin/gastrin-releasing peptide were found. These findings provide further evidence for the pathological involvement of certain neuropeptide-containing neurons in Alzheimer's disease.     

Bioactivity of soy-based fermented foods: A review

For centuries, fermented soy foods have been dietary staples in Asia and, now, in response to consumer demand, they are available throughout the world. Fermentation bestows unique flavors, boosts nutritional values and increases or adds new functional properties. In this review, we describe the functional properties and underlying action mechanisms of soy-based fermented foods such as Natto, fermented soy milk, Tempeh and soy sauce. When possible, the contribution of specific bioactive components is highlighted. While numerous studies with in vitro and animal models have hinted at the functionality of fermented soy foods, ascribing health benefits requires well-designed, often complex human studies with analysis of diet, lifestyle, family and medical history combined with long-term follow-ups for each subject. In addition, the contribution of the microbiome to the bioactivities of fermented soy foods, possibly mediated through direct action or bioactive metabolites, needs to be studied. Potential synergy or other interactions among the microorganisms carrying out the fermentation and the host's microbial community may also contribute to food functionality, but the details still require elucidation. Finally, safety evaluation of fermented soy foods has been limited, but is essential in order to provide guidelines for consumption and confirm lack of toxicity.     

Bioactive natural products from endophytes: a review

Endophytes, microorganisms that reside in the internal tissues of living plants without causing any immediate overt negative effects, have been found in every plant species examined to date and recognized as potential sources of novel natural products for exploitation in medicine, agriculture, and industry with more and more bioactive natural products isolated from the microorganisms. In this review, we focus mainly on bioactive natural products from endophytic microorganisms by their different functional roles. The prospect and facing problems of isolating natural products from endophytes are also discussed.     

Alzheimer's dementia: current data review

The review focuses on current data on Alzhemier's dementia, a clinical syndrom characterised with acquired deterioration of cognitive functioning and emotional capacities, which impaires everyday activity and quality of life. Alzheimer's dementia is the most common type of dementia in clinical surveys. The diagnosis of Alzheimer's dementia is primarily based on symptoms and signs and memory impairment is clinically most significant. Cholinesterase inhibitors -donepezil, rivastigmine and galantamine are considered to be the first line pharmacotherapy for mild to moderate Alzheimer's disease. Currently, no effective pharmacologic interventions have been researched enough to support their use in prevention of Alzheimer's dementia. Studies suggest that healthy lifestyle, ongoing education, regular physical activity, and cholesterol control, play a role in prevention of Alzheimer's dementia.     

A review on coumarins as acetylcholinesterase inhibitors for Alzheimer's disease

Acetylcholinesterase (AChE) enzyme inhibition is an important target for the management of Alzheimer disease (AD) and AChE inhibitors are the main stay drugs for its management. Coumarins are the phytochemicals with wide range of biological activities including AChE inhibition. The scientists have attempted to explore the coumarin template for synthesizing novel AChE inhibitors with additional pharmacological activities including decrease in beta-amyloid (Aβ) deposition and beta-secretase inhibition that are also important for AD management. Most of the designed schemes have involved incorporation of a catalytic site interacting moiety at 3- and 4-positions of the coumarin ring. The present review describes these differently synthesized coumarin derivatives as AChE inhibitors for management of AD.     

Simple model systems: a challenge for Alzheimer's disease

ABSTRACT: The success of biomedical researches has led to improvement in human health and increased life expectancy. An unexpected consequence has been an increase of age-related diseases and, in particular, neurodegenerative diseases. These disorders are generally late onset and exhibit complex pathologies including memory loss, cognitive defects, movement disorders and death. Here, it is described as the use of simple animal models such as worms, fishes, flies, Ascidians and sea urchins, have facilitated the understanding of several biochemical mechanisms underlying Alzheimer's disease (AD), one of the most diffuse neurodegenerative pathologies. The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of transgenic animals, has helped researchers to overcome the lack of natural models. Moreover, simple model systems of AD have been utilized to obtain key information for evaluating potential therapeutic interventions and for testing efficacy of putative neuroprotective compounds.     

Integrating the Alzheimer's disease proteome and transcriptome: a comprehensive network model of a complex disease

Network models combined with gene expression studies have become useful tools for studying complex diseases like Alzheimer's disease. We constructed a "Core" Alzheimer's disease protein interaction network by human curation of the primary literature. The Core network consisted of 775 nodes and 2,204 interactions. To our knowledge, this is the most comprehensive and accurate protein interaction network yet constructed for Alzheimer's disease. An "Expanded" network was computationally constructed by adding additional proteins that interacted with Core network proteins, and consisted of 4,945 nodes and 26,064 interactions. We then mapped existing gene expression studies to the Core network. This combined data model identified the MAPK/ERK pathway and clathrin-mediated receptor endocytosis as key pathways in Alzheimer's disease. Important proteins in the MAPK/ERK pathway that interacted in the Core network formed a downregulated cluster of nodes, whereas clathrin and several clathrin accessory proteins that interacted in the Core network formed an upregulated cluster of nodes. The MAPK/ERK pathway is a key component in synaptic plasticity and learning, processes disrupted in Alzheimer's. Clathrin and clathrin adaptor proteins are involved in the endocytosis of the APP protein that can lead to increased intracellular levels of amyloid beta peptide, contributing to the progression of Alzheimer's.