Putative Effect of Extract on Enzyme Activities Participating in Lipid and Carbohydrate Digestion Processes.

Excessive calorie intake is generally accepted as a primary cause of metabolic syndrome, and therefore a well-balanced diet and moderate exercise can be expected to be the most effective measures to avoid the disorder of energy utilization and storage. Furthermore, as any other way to improve the disorder of energy balance, it may be effective to delay and lower the digestion and/or absorption of energy sources, lipids, and carbohydrates. As a primary screening of effective substances to delay and lower the digestion and absorption processes among natural materials, the protein-deprived extract was prepared from blue-green algae , and the effect of this extract on lipase and α-glucosidase activities was examined.

Suppressive effect of Okara on intestinal lipid digestion and absorption in mice ingesting high-fat diet.

Soymilk residue Okara is paid attention as a low-calorie foodstuff effective for the amelioration of obesity, and expected to have the potential ability to reduce calorie intake by suppressing the digestion and absorption of high-calorie nutrients in the intestinal tract. Then, the direct effect of Okara extract on lipase activity was examined, and this extract was shown to inhibit the enzyme activity. On the other hand, the spray-dried powder of Okara extract was suspended in a drinking water and given to mice fed with a high-fat diet.

Lotus Root Extract Stimulates BDNF Gene Expression Through Potential Mechanism Depending on HO-1 Activity in C6 Glioma Cells.

Polyphenolic compounds have been suggested to be involved in the preservation of neural function via the production of neurotrophic factors in the brain. The nonedible joint part of lotus root (a rhizome of Nelumbo nucifera) has been reported to contain large amounts of polyphenolic compounds and, therefore, is expected to improve neural function by stimulating the production of brain-derived neurotrophic factor (BDNF) in glial cells. The effect of the aqueous extract prepared from the joint part of lotus root on BDNF gene expression was examined in C6 glioma cells as an in vitro model.

Fermented Brown Rice Extract Stimulates BDNF Gene Transcription in C6 Glioma Cells: Possible Connection with HO-1 Expression.

Fermented brown rice with Aspergillus oryzae, designated as FBRA, is known to be commercially available dietary fiber-rich food, which is appreciated as prebiotics to improve intestinal microflora, and also shown to contain various biologically active substances including polyphenolic compounds. On the other hand, polyphenolic compounds have been suggested to stimulate the expression of brain-derived neurotrophic factor (BDNF) gene in connection with the expression of heme oxidase-1 (HO-1) gene in glial cells, thus resulting in the augmentation of BDNF production in the brain, thereby being anticipated to have a putative effect on the brain function. Then, the effect of FBRA extract on HO-1 and BDNF messenger ribonucleic acid (mRNA) levels in C6 glioma cells was examined, and the extract was shown to stimulate both HO-1 and BDNF gene transcription in the glioma cells.

Soy Pulp Extract Inhibits Angiotensin I-Converting Enzyme (ACE) Activity In Vitro: Evidence for Its Potential Hypertension-Improving Action.

Soy pulp, called "okara" in Japanese, is known as a by-product of the production of bean curd (tofu), and expected to contain a variety of biologically active substances derived from soybean. However, the biological activities of okara ingredients have not yet been fully understood, and the effectiveness of okara as a functional food seems necessary to be further evaluated. Then the effect of okara extract on angiotensin I-converting enzyme (ACE) activity was examined in vitro, and the extract was shown to cause the inhibition of ACE activity in a manner depending on its concentration.

Fermented Brown Rice Extract Causes Apoptotic Death of Human Acute Lymphoblastic Leukemia Cells via Death Receptor Pathway.

Mixture of brown rice and rice bran fermented with Aspergillus oryzae, designated as FBRA, has been reported to reveal anti-carcinogenic and anti-inflammatory effects in rodents. Then, to test its potential anti-cancer activity, the aqueous extract was prepared from FBRA powder, and the effect of this extract on human acute lymphoblastic leukemia Jurkat cells was directly examined. The exposure to FBRA extract reduced the cell viability in a concentration- and time-dependent manner.

Novel antidepressant-like activity of caffeic Acid phenethyl ester is mediated by enhanced glucocorticoid receptor function in the hippocampus.

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days) has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST) and forced swim (FST) tests.

Spirulina non-protein components induce BDNF gene transcription via HO-1 activity in C6 glioma cells.

Blue-green algae are known to contain biologically active proteins and non-protein substances and considered as useful materials for manufacturing the nutritional supplements. Particularly, Spirulina has been reported to contain a variety of antioxidants, such as flavonoids, carotenoids, and vitamin C, thereby exerting their protective effects against the oxidative damage to the cells. In addition to their antioxidant actions, polyphenolic compounds have been speculated to cause the protection of neuronal cells and the recovery of neurologic function in the brain through the production of brain-derived neurotrophic factor (BDNF) in glial cells.

Polyamines cause elevation of steroid 5α-reductase mRNA levels by suppressing mRNA degradation in C6 glioma cells.

Polyamines are widely distributed in living organisms, and considered to play a potential role in various cellular processes. The effects of polyamines on gene expression as well as cell proliferation have been suggested to be closely associated with the physiological and pathological functions. However, it seems necessary to investigate their potential roles in the regulation of cellular metabolism and functions.

Novel antidepressant-like activity of propolis extract mediated by enhanced glucocorticoid receptor function in the hippocampus.

Propolis is a natural product made by honeybees that has been widely used in folk medicine with a broad spectrum of biological activities. To investigate the antidepressant-like activity of propolis extract, CD-1 mice were administered an ethanol extract of propolis (50, 100, or 200 mg/kg, p.o.

Antidepressant-like effects of Cortex Mori Radicis extract via bidirectional phosphorylation of glucocorticoid receptors in the hippocampus.

Excessive and prolonged secretion of adrenal glucocorticoids leads to a wide range of pathophysiological processes, including depression. Glucocorticoids, which act at glucocorticoid receptors (GR), are key regulators of the limbic hypothalamic-pituitary-adrenocortical (HPA) axis. In the present study, the antidepressant-like effects of the alcohol extract Cortex Mori Radicis (CMR) and its role in GR signalling were investigated.

Trichostatin A enhances glutamate transporter GLT-1 mRNA levels in C6 glioma cells via neurosteroid-mediated cell differentiation.

The neurotoxic effects of excitatory amino acids (EAAs) are suggested to be connected with the chronic loss of neuronal cells, thereby being responsible for the age-related neurodegenerative diseases. Therefore, it seems conceivable that the excitatory amino acid transporters may contribute to the protection of neuronal cells against the excitotoxic damage by facilitating the removal of EAAs from the brain tissue. On the other hand, previous studies have suggested that glial cell differentiation may be involved in the protection and recovery of neural function probably through the elevation of BDNF gene expression in the brain.

TIMP-2 fusion protein with human serum albumin potentiates anti-angiogenesis-mediated inhibition of tumor growth by suppressing MMP-2 expression.

TIMP-2 protein has been intensively studied as a promising anticancer candidate agent, but the in vivo mechanism underlying its anticancer effect has not been clearly elucidated by previous works. In this study, we investigated the mechanism underlying the anti-tumor effects of a TIMP-2 fusion protein conjugated with human serum albumin (HSA/TIMP-2). Systemic administration of HSA/TIMP-2 effectively inhibited tumor growth at a minimum effective dose of 60 mg/kg.

Extract of fermented brown rice induces apoptosis of human colorectal tumor cells by activating mitochondrial pathway.

Brown rice fermented with Aspergillus oryzae, designated as FBRA, is a dietary fiber-rich food, and fully appreciated as one of the prebiotics, which are generally considered to be beneficial to the health of the body, because of stimulating the growth and/or the activity of bacteria in the digestive system. To assess the effectiveness of FBRA as a functional food, the direct effect of FBRA extract on human colorectal tumor cells was examined. The exposure of HCT116 cells to FBRA extract reduced their viabilities in a concentration-dependent manner, and the reduction of the cell viability might be attributed to the induction of apoptosis probably through the oxidative damage to the cells.

Palytoxin causes nonoxidative necrotic damage to PC12 cells in culture.

Palytoxin (PTX) is a potent marine toxin that causies serious damage to various tissues and organs. It has been reported to affect the transport of cations across the plasma membranes, which is commonly recognized as being the principal mechanism of its highly toxic action on mammals, including humans. However, although some marine toxins have been shown to cause toxic effects on the nervous system by interfering with the transmission of nerve impulses, the effect of PTX on neuronal cells has not yet been fully elucidated.

In vitro cytotoxic effect of ethanol extract prepared from sporophyll of Undaria pinnatifida on human colorectal cancer cells.

Brown seaweed Undaria pinnatifida (Harvey) Suringar is popular as a foodstuff, and used for medical care in East Asian countries. The major components of this seaweed are shown to benefit hypertension and hyperlipidemia, and considered to reduce the risks of infarction and ischemic diseases. Furthermore, the intake of dietary fiber of seaweeds is considered to prevent the production and proliferation of cancer in the gastrointestinal tract.

Trichostatin A stimulates steroid 5alpha-reductase gene expression in rat C6 glioma cells via a mechanism involving Sp1 and Sp3 transcription factors.

The adrenergic and serotonergic stimulations of rat C6 glioma cells have previously been shown to induce the activation of steroid 5alpha-reductase (5alpha-R) gene expression, resulting in their differentiation through the production of neuroactive 5alpha-reduced steroid metabolites. In addition, progesterone and histone deacetylase (HDAC) inhibitors have also been reported to promote the glial cell differentiation with the enhancement of serotonin-stimulated brain-derived neurotrophic factor gene transcription through the production of 5alpha-reduced neurosteroids, thus suggesting that glial cell differentiation is probably implicated in the protection and survival of neuronal cells in the brain. Therefore, the expression of 5alpha-R gene in glial cells seems physiologically important in maintaining the neural function in the brain, but little is known about the mechanism underlying the regulation of 5alpha-R gene transcription.

Identification of the functional domain of glucocorticoid receptor involved in RU486 antagonism.

Mifepristone, also known as RU486, is a potent glucocorticoid receptor (GR) antagonist that inhibits GR-mediated transactivation. As an alternative to existing antidepressants, RU486 has been shown to rapidly reverse psychotic depression, most likely by blocking GR. Although a number of studies have demonstrated RU486-induced GR antagonism, the precise mechanism of action still remains unclear.

Immunohistochemical studies on early stage of hepatic damage induced by subacute inhalation of toluene vapor in rats.

Toluene is one of the most widely used organic solvents and is commonly recognized as a noxious substance inducing chronically toxic damage to neural, hepatic and renal functions in the workers engaged in printing and painting. Although hepatic cells are generally considered to be vulnerable and susceptible to various organic solvents, particularly chloroform and other halogenated hydrocarbons, the hepatotoxic effects of aromatic hydrocarbons including toluene have not yet been sufficiently characterized. In particular, it still seems unclear whether toluene itself can directly act on hepatic cells, inducing toxic damage to their metabolism and function.

Histone deacetylase inhibitors promote neurosteroid-mediated cell differentiation and enhance serotonin-stimulated brain-derived neurotrophic factor gene expression in rat C6 glioma cells.

Progesterone treatment has previously been reported to promote the differentiation of glial cells probably through the production of 5alpha-reduced neurosteroids, resulting in the enhancement of serotonin-stimulated brain-derived neurotrophic factor (BDNF) gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain and hence has been suggested to improve mood disorders and other symptoms in depressive patients. Based on these previous observations, the effects on glial cells of histone deacetylase (HDAC) inhibitors, which are known as agents promoting cell differentiation, were examined using rat C6 glioma cells as a model for in vitro studies. Consequently, trichostatin A (TSA), sodium butyrate (NaB), and valproic acid (VPA) stimulated glial fibrillary acidic protein (GFAP) gene expression, and their stimulatory effects on GFAP gene expression were inhibited by treatment of these cells with finasteride, an inhibitor of the enzyme producing 5alpha-reduced neurosteroids.

Production of apoptosis-inducing substances from soybean protein by Clostridium butyricum: characterization of their toxic effects on human colon carcinoma cells.

Microbial metabolism of soybean constituents is known to produce novel active substances as a chemopreventive agent during the fermentation, and enterobacteria are expected to produce chemopreventive agents as a consequence of metabolizing soybean constituents in the intestinal tract. Then, the conditioned medium was prepared by culturing an enterobacterium Clostridium butyricum (C. butyricum) with soybean protein, and its direct effect on human colon carcinoma HCT116 cells was examined.

Possible relation of hemin-induced HO-1 expression to the upregulation of VEGF and BDNF mRNA levels in rat C6 glioma cells.

Glial cells are generally considered to contribute to retaining the integrity of neural function through the protection of neuronal cells against neurodegenerative insults and also expected to play a potential role in the protection of cerebrovascular systems from various toxic insults of hemorrhaged blood, thus proposing a possible implication of glial cells in the recovery of brain function from the damage caused by cerebral hemorrhage. Based on this hypothetical idea, the direct effect of hemin on the expression of genes encoding heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) in glial cells was examined using rat C6 glioma cells as an in vitro model system. Hemin elevated both HO-1 and VEGF mRNA levels in the glioma cells at the concentration causing no critical damage to the cells, and the elevation of BDNF mRNA levels was also observed by exposing the cells to hemin under the same conditions.

Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in rat c6 glioma cells through production of 5alpha-reduced neurosteroids.

Tricyclic antidepressants and selective serotonin reuptake inhibitors are considered in theory to induce the outflow of neurotransmitters, norepinephrine, and serotonin from the synapses as a consequence of inhibiting their reuptake into the nerve terminals, resulting in the stimulation of glial cells surrounding the synapses in the brain. Then, we have investigated the direct actions of neurotransmitters on glial cell metabolism and function using rat C6 glioma cells as an in vitro model system and suggested that these neurotransmitters induce their differentiation probably through the production of 5alpha-reduced neurosteroids. On the other hand, the stimulation of the glioma cells with serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) gene expression, which may be closely related to the beneficial effects of antidepressant drugs.

Desipramine induces apoptotic cell death through nonmitochondrial and mitochondrial pathways in different types of human colon carcinoma cells.

Cytotoxic effects of desipramine on human colon carcinoma HT29 and HCT116 cells were examined. Desipramine reduced the viability of HT29 cells in a concentration-dependent manner, but failed to cause any significant change in the viability of HCT116 cells by the concentration up to 50 mumol/l, at which an approximately 60% reduction of the viability of HT29 cells was observed. Despite their different sensitivities, desipramine caused the nonoxidative apoptotic damage to both of them.

High salt culture conditions inhibit serum- and NGF- but not PMA-induced Egr-1 gene transcription in rat C6 glioma cells.

Recent studies have suggested that glial cells may play a physiologically important role in the retention and restoration of neuronal cell integrity, proposing the possibility that the proliferation and/or differentiation of glial cells may be related to pathological changes in neural functions in neurodegenerative diseases, and hence, it seems interesting to investigate the expression of genes related to the proliferation and differentiation of glial cells. Following this basic concept, we have previously examined the influence of culture conditions on egr-1 gene expression in rat C6 glioma cells and have shown that brief exposure of these cells to high salt culture medium can induce the down-regulation of egr-1 gene expression. In contrast, the long-term culture of these cells in high salt medium has been shown to primarily reduce their proliferation and secondarily elevate egr-1 gene transcription as a consequence of arresting the cell-cycle progression.