phytoestrogens and Neurodegenerative-Diseases

Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction.

Topics: Antineoplastic Agents; Coffee; Curcumin; Diet; Epigenesis, Genetic; Folic Acid; Food; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Metabolic Syndrome; Neoplasms; Neurodegenerative Diseases; Phytoestrogens; Polyphenols; S-Adenosylmethionine; Selenium; Trace Elements; Vitamin B 12; Vitamin B Complex; Vitamins

Recent large clinical trials demonstrating deleterious effects of postmenopausal hormone replacement therapy have raised interest in the use of food products and extracts containing phytoestrogens as potential safe alternatives for menopausal symptoms, age-related cognitive decline and neurodegenerative diseases. While numerous preclinical studies and various clinical trials point to beneficial effects of estrogens on the brain, phytoestrogens from several sources share many of these estrogenic effects, in addition to having unique activities distinct from natural estrogens. Numerous in vitro and in vivo studies show potential neuroprotective properties of phytoestrogens on the brain in conditions ranging from aging to neurodegenerative disease and cerebral ischemia. Although dosage, timing and safety concerns remain to be addressed before their therapeutic use in human populations can be recommended, their safety profile and some intriguing studies on human cognition in aging suggest that further clinical study of these compounds for brain health is warranted.

Topics: Animals; Cell Line; Disease Models, Animal; Humans; Molecular Structure; Neurodegenerative Diseases; Neuroprotective Agents; Phytoestrogens

Estrogens are pleiotropic hormones having an influence not only on reproductive system and sexual functions. These hormones are synthesized not only by ovaries, but also by glia in central nervous system (CNS) and Schwann cells in peripheral nervous system. Therefore they create microenvironment having a wide spectrum of effects such as neuroprotective and antiapoptotic or supporting neurogenesis and regeneration. Mechanisms of estrogens activity are both genomic and quick non-genomic transmitted through second intracellular messengers. There is evidence for protective action of estrogens in neurodegenerative diseases and other diseases of CNS. Nevertheless there are still secrets in estrogens nature. This fact pushes us to ask more questions and continue scientific research to look for the answer.

Topics: Alzheimer Disease; Animals; Central Nervous System; Estradiol; Estrogens; Female; Fertility; Gene Expression Regulation, Enzymologic; Humans; Male; Mood Disorders; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Phytoestrogens; Rats; Receptors, Estrogen

Background Neuroinflammation is one of the main causes of neurodegenerative events. Phytoestrogen is a group compounds that have an estrogen-like structure or function. Phytoestrogen has a high potential to overcome neuroinflammation caused by estrogen deficiency in postmenopausal women. Marsilea crenata Presl. is a plant known to contain phytoestrogens. This research aimed to analyze the activity of an n-butanol fraction of M. crenata leaves in inhibiting the classical pathway activation of microglia HMC3 cell line to M1 polarity, which has proinflammatory characteristics. Methods Microglia HMC3 cell line was cultured in Eagle's minimum essential medium and induced with IFN-γ for 24 h to activate the cell to M1 polarity in 24-well microplates. The n-butanol fraction was added with various doses of 62.5, 125, and 250 ppm and genistein 50 μM as a positive control. The expression of major histocompatibility complex II (MHC II) as a marker was tested using a confocal laser scanning microscope. Results The result of MHC II measurement shows a significant difference in the MHC II expression in the microglia HMC3 cell line between the negative control and all treatment groups at p<0.05, indicating a non-monotonic dose-response profile. Conclusions The best dosage to inhibit MHC II expression was 250 ppm with the value of 200.983 AU. It is then concluded that n-butanol fraction of M. crenata leaves has antineuroinflammation activity due to its phytoestrogens.

Topics: 1-Butanol; Cell Line; Histocompatibility Antigens Class II; Humans; Inflammation; Marsileaceae; Microglia; Neurodegenerative Diseases; Phytoestrogens; Plant Extracts

Genistein is a soy-derived isoflavone and phytoestrogen with antioxidant and neuroprotective activity. Genistein has intrinsically low oral bioavailability that affects its dose-response activities.. Nanotechnologies were used to obtain the delivery of genistein to the brain: lipid-based nanovesicles, transfersomes, loaded with the phytoestrogen were developed as potential therapeutic or preventive strategy against neurodegenerative diseases by intranasal administration.. Phosphatidylcholine from soybean and different edge activators were used to prepare transfersomes. The effect of selected nanovesicles on the oxidative damage was studied in PC12 cell line.. Suitable nanovesicles as carrier of genistein were obtained; their composition affects deformability, drug permeation behavior and cytotoxicity. In particular, the formulation containing Span 80, GEN-TF2, showed efficiency of internalization into the cell and it was able to attenuate ROS formation and to reduce the amount of apoptotic cells generated by H. GEN-TF2 was able to reduce the oxidative damage suggesting a possible antioxidant role of this drug delivery system. These obtained data confer to GEN-TF2 a potential antioxidant activity and then it could be used as adjuvant therapy in oxidative stress-related neurodegenerative diseases.

Topics: Adjuvants, Pharmaceutic; Animals; Antioxidants; Drug Carriers; Genistein; Hydrogen Peroxide; Nanostructures; Neurodegenerative Diseases; Oxidation-Reduction; Oxidative Stress; PC12 Cells; Phytoestrogens; Rats

Microglial activation has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and HIV encephalopathy. Phytoestrogens have been shown to be neuroprotective in neurotoxicity models; however, their effect on microglia has not been well established. In the current study, we report that the soy phytoestrogens, genistein, daidzein, and coumestrol, decreased nitric oxide (NO) production induced by lipopolysaccharide (LPS) in the rat microglial cell line (HAPI). The levels of inducible NO synthase (iNOS) mRNA and protein expression were also reduced. Transcription factors known to govern iNOS expression including interferon regulatory factor-1 (IRF-1) and phosphorylated STAT1 were down regulated. These observations explain, at least in part, the inhibitory effect of phytoestrogens on NO production. The levels of monocyte chemoattractant protein-1 and interleukin-6 mRNA, proinflammatory chemokine and cytokine associated with various neurological disorders, were also reduced following LPS stimulation when HAPI cells were pretreated with phytoestrogens. Hence, genistein, daidzein, and coumestrol could serve as anti-inflammatory agents and may have beneficial effects in the treatment of neurodegenerative diseases.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Transformed; Chemokine CCL2; Disease Models, Animal; Gene Expression Regulation; Glycine max; Interferon Regulatory Factor-1; Interleukin-6; Lipopolysaccharides; Microglia; Neurodegenerative Diseases; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type II; Phytoestrogens; Rats; STAT1 Transcription Factor

To investigate the mechanism underlying the neurodegeneration of postmenopausal women, the effect of genistein on hippocampal neurodegeneration was investigated in ovariectomized (OVX) Sprague-Dawley rats. Three-month-old female Sprague-Dawley rats were randomly divided into four groups: sham operated; OVX only; genistein-treated OVX (OVX-genistein); and estradiol benzoate-treated OVX (OVX-EB). Genistein and EB were subcutaneously injected into rats of the OVX-genistein and OVX-EB groups, respectively, once a day from the second day after surgery. Behavioral testing began on day 31 after surgery and lasted 5 d. The activities of superoxide dismutase and content of malondialdehyde in serum, the concentration of intrasynaptosome-free calcium, membrane relative viscosity of cerebral synaptosomes, and mean optical density (MOD) of the hippocampal synaptophysin immunoreactivity product were measured, respectively, in the eighth week after surgery. It was found that the escape latency in the OVX-EB and the OVX-genistein groups was significantly lower than that in the OVX control group (p < 0.05), whereas in the behavioral test, the platform-passing number was higher than in the OVX control group (p < 0.05). [Ca2+]i in the cerebral cortical and hippocampal synaptosome of the OVX-only group was remarkably higher than that in the other three groups ( p < 0.01). The hippocampal synaptosome membrane viscosity of the OVX-only group was significantly higher than that in the sham-operated, OVX-EB (p < 0.05) and the OVX-genistein (p < 0.01) groups. The MOD of synaptophysin immunoreactive product in the radiation layers of CA1, CA2, CA3 and the molecular layer of the dentate gyrus of the OVX-only group was significantly lower than in the sham-operated, OVX-genistein, and OVX-EB groups (p < 0.01). These results suggested that genistein, which has antioxidant properties similar to estradiol, could be used as a substitute for estradiol to prevent or treat central neurodegeneration in postmenopausal women.

Topics: Animals; Calcium; Female; Genistein; Hippocampus; Male; Malondialdehyde; Maze Learning; Membrane Fluidity; Memory; Neurodegenerative Diseases; Ovariectomy; Phytoestrogens; Random Allocation; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Synapses; Synaptosomes

Although experimental evidence has shown that the neuroprotective effect from estrogen may benefit postmenopausal women, but the clinical use of estrogen was limited by the risk of increasing the cases of mammary and endometrial cancer. This study was designed to evaluate the neuroprotective effects of a novel phytoestrogen alpha-zearalanol (alpha-ZAL), on the cultured rat hippocampal neurons. Following a 24-h exposure of the cells to amyloid beta-peptide fragment 25-35 (A beta 25-35), a significant reduction in cell survival and activities of total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as increased of malondialdehyde (MDA) were observed. Preincubation of the cells with alpha-ZAL or 17 beta-estradiol(17 beta-E2) prior to A beta 25-35 exposure elevated the cell survival and SOD and GSH-Px activities, and decreased the level of MDA. These data suggested that the phytoestrogen alpha-ZAL, like estrogen, may effectively antagonize A beta 25-35-induced cell toxicity, which might be beneficial for neurons.

Topics: Amyloid beta-Peptides; Animals; Antioxidants; Cell Death; Cell Survival; Cells, Cultured; Estradiol; Estrogens; Glutathione Peroxidase; Hippocampus; Malondialdehyde; Neurodegenerative Diseases; Neurons; Oxidative Stress; Peptide Fragments; Phytoestrogens; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Zeranol

ERbeta has been associated with estrogen-induced promotion of memory function and neuronal survival. Based on the optimized complex structure of human ERbeta LBD bound with genistein, computer-aided structure-based virtual screening against a natural source chemical database was conducted to determine the occurrence of plant-based ERbeta-selective ligands. Twelve representative hits derived from database screening were assessed for their binding profiles to both ERs, three of which displayed over 100-fold binding selectivity to ERbeta over ERalpha.

Topics: Aging; Benzopyrans; Binding Sites; Binding, Competitive; Databases, Factual; Estrogen Receptor alpha; Estrogen Receptor beta; Fluorescence Polarization; Genistein; Humans; Ligands; Models, Molecular; Neurodegenerative Diseases; Neuroprotective Agents; Phytoestrogens; Plants; Protein Conformation; Quantitative Structure-Activity Relationship