Estrogen is neuroprotective against hypoglycemic injury in murine N38 hypothalamic cells.

Estrogen (E2) has been demonstrated to possess protective effects from hypoglycemic toxicity, particularly in the pancreas. In the central nervous system, several brain regions, such as the hypothalamus, are highly vulnerable to hypoglycemic injuries that may lead to seizures, coma, and mortality. The present study performed a novel in vitro assay of hypoglycemic injury to hypothalamic cells, and is the first study, to the best of our knowledge, to demonstrate that E2 protects hypothalamic cells from hypoglycemic toxicity. The toxic effects of hypoglycemia on hypothalamic cells in vitro was determined by performing cell counts, together with MTT and lactate dehydrogenase assays, using the N38 murine hypothalamic cell line. Following 24 and 48 h in hypoglycemic conditions, a 60 and 75% reduction in cell number and mitochondrial function was observed, which reached 80 and ~100% by 72 and 96 h, respectively. E2 treatment prevented the hypoglycemia­induced loss in cell number and mitochondrial toxicity at 24 and 48 h. However at 72 and 96 h of hypoglycemic conditions, the neuroprotective effects of E2 on cell number or mitochondrial function was not significant or not present at all. In order to determine whether E2 exerted its effects through the AKT signaling pathway, the expression of proline­rich AKT substrate of 40 kDa (PRAS40) was analyzed. No alterations in PRAS40 expression were observed when N38 cells were exposed to hypoglycemic shock. From the biochemical and molecular data obtained, the authors speculated that E2 exhibits neuroprotective effects against hypoglycemic shock in hypothalamic cells, which dissipates with time. Despite demonstrating no significant effect on total AKT/PRS40 activity, it is possible that E2 may mediate these neuroprotective effects by upregulating the phosphorylated­AKT/pPRAS40 signaling pathway. The present study presented, to the best of our knowledge, the first in vitro model for hypoglycemic toxicity to hypothalamic cells, and provided evidence to suggest that E2 may protect hypothalamic cells from the damaging effects of hypoglycemia.

Dietary selenium and selenoprotein function.

Selenium is a trace mineral and an essential nutrient in the human diet. Selenium is found in soil and water and consequently enters the food chain through the root ways of plants and aquatic organisms. Some areas of the world are low in soil selenium resulting in a selenium deficient population and the appearance of an associated heart disease and bone disorders that can be corrected with dietary selenium. Indeed the requirement for dietary selenium was established by these observations and while selenium deficiency is rare in the West, patients requiring long-term intravenous feedings have also show heart disease associated with a deficiency of selenium in the feeding fluids. Subsequently, it has been established that dietary selenium can improve a wide range of human health conditions even in areas with soil replete in selenium.

Dietary and botanical anxiolytics.

Drugs used to treat anxiety have many negative side effects including addiction, depression, suicide, seizures, sexual dysfunction, headaches and more. Anxiolytic medications do not restore normal levels of neurotransmitters but instead manipulate the brain chemistry. For example, selective serotonin reuptake inhibitors (SSRIs) prevent the reuptake of serotonin from the synapse allowing serotonin to remain in the area of activity for a longer period of time but does not correct the lack of serotonin production. Benzodiazepines, such as Valium and Xanax®, stimulate GABA receptors, thus mimicking the calming effects of GABA but again do not fix the lack of GABA production. Often, the brain becomes accustomed to these medications and they often lose their effectiveness, requiring higher doses or different drugs. In contrast to anxiolytic drugs, there are herbs and nutrients which can stimulates neurotransmitter synthesis and more naturally effect and even adjust brain chemistry in the absence of many of the side effects experienced with drugs. Therefore this paper explores several herbal and nutritional approaches to the treatment of anxiety.

Formulations of dietary supplements and herbal extracts for relaxation and anxiolytic action: Relarian.

Dietary supplements are widely used for desired effects on memory, insomnia, mood and anxiety. This review focuses on supplements which have anxiolytic or mild relaxation properties and enhance mood. For example, Kava (Piper methysticum) is reported to have anaxiolytic actions and to reduce tension through skeletal muscle relaxation. Dried passion flower (genus Passiflora) is reported to reduce insomnia and hysteria. Skullcap (genus Scutellaria), hops (Humulus lupulus), lemon balm (Melissa officinalis) and Valerian (Valeriana officinalis) root are all herbs reported as anaxiolytic calming agents. Further, extracts of Magnolia and Phellondendron bark are mild sedatives. Supplements such as gamma-aminobutyric acid (GABA), theanine, tryptophan and 5-hydroxytryptophan (5-HTP) are reported to promote relaxation. In general, these supplements appear to act as GABA receptor agonists or to boost GABA levels, although Kava inhibits both norephinephrine uptake and sodium and potassium channels and 5-HTP may act through elevation of serotonin. While questions remain in the literature regarding the medicinal value of these supplements in treating mood and anxiety disorders, based on cellular and animal studies as well as human clinical trials the literature supports a role for these preparations as useful alternatives in the management of the stress and anxiety of everyday life.

Natramune and PureWay-C reduce xenobiotic-induced human T-cell alpha5beta1 integrin-mediated adhesion to fibronectin.

BACKGROUND: In vitro and in vivo studies demonstrate that nutritional supplementation reduces inflammation and inflammatory markers associated with T-cell adhesion mechanisms. Here, we investigate the effects of the nutritional supplements, Natramune (PDS-2865) and PureWay-C, on xenobiotic-induced alpha5beta1 integrin-mediated T-cell adhesion to fibronectin. MATERIAL/METHODS: The human CD4+ lymphoblastoid cell line CEM SS was treated with combinations of bifenthrin, blocking antibodies to human beta1 and alpha5 integrin, and nutrient supplements. After 30 minutes unattached cells were aspirated and the percent of attached cells was determined. RESULTS: Bifenthrin stimulated T-cell adhesion to fibronectin at concentrations between 1.0 and 100 microM with a maximal stimulation of 8.3-fold at 10 microM. At 500 microg/ml, Natramune reduced 100 microM bifenthrin-induced adhesion by nearly 90%. PureWay-C reduced by 1.5-fold the level of T-cell adhesion stimulated by bifenthrin concentrations of both 10 microM and 100 microM. The combination of Natramune and PureWay-C resulted in a 6.3 and 7.5-fold inhibition at 10 microM and 100 microM bifenthrin respectively. Antibody blocking studies demonstrated that bifenthrin induced CEM SS adhesion to fibronectin is mediated through alpha5beta1 integrin. Inhibition of T-cell adhesion achieved by anti-integrin antibodies was further reduced with 50 and 500 microg/ml Natramune treatment. Pretreatment of fibronectin with Natramune did not alter induced T-cell adhesion to fibronectin. CONCLUSIONS: These data demonstrate that xenobiotic-induced alpha5beta1 integrin mediated T-cell adhesion to fibronectin is reduced by nutritional supplementation with Natramune (PDS-2865) and PureWay-C. These data suggest the possibility that inflammatory responses associated with exposure to pollutants can be mitigated by nutritional supplementation.

A novel vitamin C preparation enhances neurite formation and fibroblast adhesion and reduces xenobiotic-induced T-cell hyperactivation.

BACKGROUND: Vitamin C (ascorbic acid, ascorbate) has been shown to enhance neurite outgrowth, promote fibroblast adhesion during wound healing, and reduce xenobiotic-induced leukocyte hyperactivity and inflammatory damage. In this study, a comparison was made between Ester-C and PureWay-C on these various cellular activities. MATERIAL/METHODS: PC12 cells were stimulated to form neurites with nerve growth factor, NIH 3T3 fibroblasts were seeded on fibronectin and H9 T-cells were stimulated to aggregate with the pyrethroid pesticide bifenthrin. The rate of neurite formation, fibroblast adhesion and T-cell homotypic aggregation was then measured in the absence and presence of various formulations of vitamin C including Ester-C and PureWay-CTM. RESULTS: With PureWay-C treatment, 12% of PC12 cells extended neurites within one hour of treatment and 45% of the cells extended neurites by hour nine. With Ester-C, 0% and 15% extended neurites at one and nine hours, respectively. NIH-3T3 fibroblast adhesion to fibronectin was enhanced by 4.7-fold with a 30 minute PureWay-CTM treatment while Ester-C increased fibroblast adhesion by only 1.5 fold. Further, PureWay-CTM reduced pesticide-mediated T-cell homotypic aggregation by 83% within 30 minutes of treatment while the reduction seen with Ester-C was only 33%. CONCLUSIONS: These data confirm the previous observations that vitamin C supplementation can promote neurite outgrowth, increase fibroblast adhesion and reduce xenobiotic induce immunocytes aggregation. More importantly, these data show that PureWay-C has a faster and greater beneficial effect on these parameters when compared to other vitamin C formulations.

PolicosanolPlus and Neuroprevin ameliorate pesticide-mediated inhibition of neurite outgrowth and neurite degeneration.

BACKGROUND: Pesticide exposure is a recognized risk factor for neurodegenerative diseases. Recently, bifenthrin, a pyrethroid pesticide, was shown to inhibit the formation of neurites and cause neurite retraction, raising concern that these newer and less toxic pesticides may also contribute to neurodegenerative diseases. PolicosanolPlus and Neuroprevin are nutraceutical supplements which promote the survival of neurites in neuronal cell cultures. Here we determine if PolicosanolPlus and Neuroprevin can ameliorate the neurodegenerative effects of bifenthrin. MATERIAL/METHODS: PC12 cells were treated with NGF, bifenthrin, PolicosanolPlus and Neuroprevin in various combinations and the formation of neurites was assessed microscopically at times ranging from 12 to 72 hours post treatment. Bifenthrin was also withheld at the time of NGF, PolicosanolPlus and Neuroprevin treatment and added after neurite formed to assess neurite retraction. RESULTS: Bifenthrin (1 x 10(-6) M) inhibits neurite outgrowth, in the absence of cell death, by more than 50% at 12 hours and by more than 80% at 72 hours. With addition of PolicosanolPlus and/or Neuroprevin at the time of cell seeding, bifenthrin does not inhibit neurite outgrowth. Addition of bifenthrin to differentiated cells results in a retraction of 90% of neurites, while those with PolicosanolPlus and Neuroprevin show no significant retraction of neurites. CONCLUSIONS: The pesticide, bifenthrin, inhibits neurite formation and causes neurite retraction. PolicosanolPlus and Neuroprevin are nutraceutical supplements which ameliorate the effects of bifenthrin on neurite outgrowth and retraction. Dietary supplementation with PolicosanolPlus and Neuroprevin may protect against developmental and long-term neurodegenerative events that result from exposure to pesticides.