bluuebunny/crossref_metadata_2025 huggingface dataset:
Vanadium and diabetes
Authors: Thompson Katherine H.
Published: December 2008

Vanadium is an ultratrace element, widely distributed in nature, yet with no presently known specific physiological function in mammals. The apparent role of vanadium in regulation of intracellular signaling, as a cofactor of enzymes essential in energy metabolism, and as a possible therapeutic agent in diabetes is of increasing interest as more and more research reports present evidence of vanadium's potentially unique biological function. In this mini‐review, the author summarizes current knowledge of the bioinorganic chemistry of vanadium, the basic features of diabetes mellitus and its metabolic sequelae, and the in vitro and in vivo effects of both inorganic and organically‐chelated vanadium compounds. Results of clinical trials to date, as well as kinetic studies of tissue uptake are covered. Examples of ways to enhance the positive effects of vanadium as an oral therapeutic adjunct in diabetic control, while minimizing potential toxicity, are compared with regard to desirable features and possible drawbacks.
Copper and signal transduction: Platelets as a model to determine the role of copper in stimulus‐response coupling
Authors: Thomas Johnson W.
Published: December 2008

Platelets from copper‐deficient rats have been used as a model to investigate the role of copper in receptor‐mediated cellular responses. Copper deficiency doubles the rate of dense granule secretion and increases myosin association with the platelet cytoskeleton following thrombin stimulation. Mechanisms underlying the effects of copper deficiency on thrombin‐ induced signals that elicit dense granule secretion involve suppression of protein kinase C activity and impairment of Ca2+ release from intracellular stores. Copper deficiency also reduces the cellular GTP content of platelets. This may limit receptor effector coupling through GTP‐dependent regulatory proteins leading to protein kinase C activation and the release of Ca2+ from intracellular stores. The reduction in GTP content during copper deficiency results from its utilization to maintain cellular ATP levels in response to severely inhibited cytochrome c oxidase activity in platelet mitochondria. Thus, the role of copper in maintaining normal signal transduction may be indirectly related to its biological function in mitochondria.
Influence of dietary nucleotides on plasma immunoglobulin levels and lymphocyte subsets of preterm infants
Authors: Navarro J. , Maldonado J. , Narbona E. , Ruiz‐Bravo A. , García Salmerón J. L. , Molina J. A. , Gil A.
Published: December 2008

We examined the effects of nucleotide supplementation to a preterm adapted milk formula on the lymphocyte subsets and plasma IgG, IgM and IgA levels in preterm infants for the first three months of life. Two groups of preterm infants received a milk formula or the same formula supplemented with CMP, AMP, UMP, GMP and IMP to mimic the concentration of acid‐soluble nucleotides found in human milk. Blood samples were obtained at birth, 10 days, 20—30 days and 3 months of age. Preterm infants fed the nucleotide formula exhibited higher plasma levels of IgM in all postnatal study periods than neonates fed the standard formula; moreover, IgA was also higher at 3 months of age in nucleotide formula fed infants. No major differences were seen between groups for IgG levels and lymphocyte subsets. Thus, dietary nucleotides appear to exert actions on immature human neonate lymphocytes enhancing the in vivo production of Ig which may have a role in the defense capacity of neonates.
Lipid soluble vitamins in gene regulation
Authors: Carlberg Carsten
Published: December 2008

Vitamin A (retinol) and vitamin D are lipid soluble vitamins that are precursors of the nuclear hormones all‐trans retinoic acid (RA) and 1α,25‐dihydroxyvitamin D3 (VD) that bind with high affinity to their cognate nuclear receptors, referred to as retinoic acid receptor (RAR) and vitamin D receptor (VDR). Both types of nuclear receptors are structurally related and belong to the same subclass of the nuclear receptor superfamily, a large family of ligand‐inducible transcription factors. Both RAR and VDR form heterodimers preferentially with the nuclear receptor for 9‐cis RA, referred to as the retinoid X receptor (RXR), but functional RAR‐VDR heterodimers have also been observed. Moreover, both types of nuclear receptors interact in a ligand‐dependent fashion with members of the same class of co‐activator, co‐repressor and co‐integrator proteins. These similar molecular mechanisms of action provide several possibilities for an interaction of RARs with VDR that are all based on allosteric protein—protein interactions. These interactions can result in either an additive or a transrepressive functional interference between RA and VD. The two remaining lipid soluble vitamins, vitamins E and K, are not known to interact with nuclear receptors, but their structure does not exclude this possibility. Moreover, for vitamin E modulatory effects on transcription factors, such as AP‐1, have been described. This review will discuss briefly gene regulation by the four lipid soluble vitamins.
Ubiquinone redox cycle as a cellular antioxidant defense system
Authors: Kishi Takeo , Takahashi Takayuki , Usui Akinori , Okamoto Tadashi
Published: December 2008

Ubiquinone (UQ) reductase responsible for reduction of non‐mitochondrial UQ was investigated in rats toward demonstrating an antioxidant role of UQ. In the liver, most of cellular UQ‐10 reductase activity was attributable to a novel NADPH‐UQ reductase in cytosol. The enzyme was not inhibited by dicumarol and rotenone, and had a Km of 19 μM for NADPH and 307 μM for NADH at the optimum pH 7.4. The enzyme was purified 300‐fold to apparent homogeneity from the liver cytosol by an affinity chromatographic method. The purified enzyme reduced UQ‐10 in lecithin liposomes, and protected the liposomes from lipid peroxidation. Furthermore, supplementation of rats with UQ‐10 was observed to increase the enzyme level in their livers without affecting levels of other antioxidant factors. The observations suggested that cytosolic NADPH‐UQ reductase is responsible for cellular UQ redox cycle as an endogenous antioxidant.
Effect of vitamin E on production of macrophage migration inhibitory factor (MIF) by macrophages
Authors: Sakamoto Wataru , Nishihira Jun , Fujie Katsutoshi , Iizuka Tadashi , Handa Hiroshi , Ozaki Mitsuru , Yukawa Susumu
Published: December 2008

Macrophage migration inhibitory factor (MIF), a putative cytokine involved in inflammatory and immune responses, was identified in rat peritoneal macrophages by Western blot analysis and its secretion into culture medium by enzyme‐linked immunosorbent assay. To clarify the possibility of vitamin E as an immune modulator, we investigated the effect of vitamin E on MIF production in macrophages in response to calcium ionophore A23187 and lipopolysaccharide (LPS). Intraperitoneal injections of vitamin E (5 mg per rat) for 6 successive days resulted in a significant increase of α‐tocopherol content in peritoneal macrophages. α‐Tocopherol content of macrophages in vitamin E‐treated rats was 478.3 ± 90.7 ng/106 cells, whereas in control rats it was 1.5 ± 0.5 ng/106 cells. For the control macrophages, total MIF content of the medium (2.5 × 106 cells/18 ml) without stimulation was 40.7 ± 3.6 ng after 14 h culture, whereas stimulation with calcium ionophore A23187 (400 nM) and LPS (5.0 μg/ml) induced the elevation of MIF content to 65.9 ± 7.5 ng and 74.3 ± 10.4 ng, respectively (p<0.05, n=3). On the other hand, vitamin E‐enriched macrophages without stimulation showed less MIF content (14.0 ± 4.2 ng) than the control (p<0.05, n=3). Similarly, the increase of MIF of vitamin E‐treated macrophages was significantly suppressed after stimulation with calcium ionophore A23187 or LPS, compared with the control macrophages (p<0.01, n=3). From analysis of intracellular MIF content by Western blot, we found no alteration of intracellular MIF content of vitamin E‐macrophages, in contrast to the decreased content of control stimulated‐macrophages, showing that vitamin E suppressed MIF secretion into the culture medium. Taken together, these results indicate that vitamin E may contribute to the regulation of inflammatory and immune responses through regulation of MIF secretion, possibly by modulating macrophage‐membrane architecture.
Interleukin‐1 signaling is dependent on free thiols
Authors: Böl Gaby‐Fleur , Tewes Frank , Brigelius‐Flohé Regina
Published: December 2008

Stimulation of the Interleukin‐1 receptor type I (IL‐1‐RI) with IL‐1 activates an associated serine/threonine kinase, IRAK, which phosphorylates downstream targets, resulting in NF/kappaB activation. The signaling cascade is accompanied by oxidative processes and contains putative targets for redox regulation. Preincubation of the murine T cell line EL‐4 and the human umbilical cord vein endothelial cell line ECV 304 with thiol modifying compounds like diamide, menadione or phenylarsine oxide inhibited the IL‐1‐induced phosphorylation of an endogenous substrate with a molecular mass of 60 kD. In the endothelial cell line, a second target of about 85 kD was phosphorylated after IL‐1 stimulation, which was also inhibited by thiol modification. These data suggest that IL‐1 signal transduction depends on free thiols which might be targets for redox regulation not only in lymphocytes, but also in endothelial cells.
Biosynthesis of selenophosphate
Authors: Lacourciere Gerard M.
Published: December 2008

Selenophosphate synthetase, the product of the selD gene, produces the highly active selenium donor, monoselenophosphate, from selenide and ATP. Positional isotope exchange experiments have shown hydrolysis of ATP occurs by way of a phosphoryl‐enzyme intermediate. Although, mutagenesis studies have demonstrated Cys17 in the Escherichia coli enzyme is essential for catalytic activity the nucleophile in catalysis has not been identified. Recently, selenophosphate synthetase enzymes have been identified from other organisms. The human enzyme which contains a threonine residue corresponding to Cys17 in the E. coli enzyme, has been overexpressed in E. coli. The purified enzyme shows no detectable activity in the in vitro selenophosphate synthetase assay. In contrast, when the human enzyme is expressed to complement a selD mutation in E. coli, in the presence of 75Se, incorporation of 75Se into bacterial selenoproteins is observed. The inactive purified human enzyme together with the very low determined specific activity of the E. coli enzyme (83 nmol/min/mg) suggest an essential component for the formation of selenophosphate has not been identified.
Iodine and brain development
Authors: Bernal Juan
Published: December 2008

The development of the brain is critically dependent on an adequate supply of iodine. Iodine is an integral part of thyroid hormone, which acts on brain development by regulating the expression of target genes. The active thyroid hormone, T3, is generated in part in the thyroid gland, but about 80% of T3 in brain is formed locally from T4 deiodination mainly by the action of a specific iodothyronine deiodinase. This enzyme is highly expressed in astrocytes, which take up T4 from the blood and deliver T3 for neuronal use. In the target cells T3 binds to nuclear receptors which are transcription factors. The T3 receptors are expressed in the brain before fetal thyroid gland function and may be activated by maternal thyroid hormone during midgestation. Although a group of thyroid hormone target genes has been identified in recent years, many basic questions of thyroid hormone action in the brain remain to be elucidated.
Relationship between dietary copper concentration and acetylcholine‐induced vasodilation in the microcirculation of rats
Authors: Schuschke D. A. , Percival S. S. , Saari J. T. , Miller F. N.
Published: December 2008

Dietary copper deficiency has been shown to significantly reduce acetylcholine (Ach)‐induced vascular smooth muscle relaxation. The current study was designed to examine the relative relationship between dietary copper and the vasodilator response to Ach in the microcirculation of the rat. Male weanling rats were fed a purified basal diet supplemented with 6.0, 3.0, 1.5 or 0.0 μg Cu/g diet for 4 weeks to provide an adequate, two marginal, and deficient intakes of dietary copper. Arteriole dilation in response to increasing concentrations of acetylcholine (10−1 to 10−4 M) was measured in the in vivo cremaster muscle microcirculation for each dietary group. Liver copper and both aortic and erythrocyte Cu,Zn‐SOD activity were used as indices of systemic copper status. Dilation to the increasing concentrations of Ach was only different in the 0 μg Cu supplemented group compared to the copper‐adequate control values. However, the combined results showed an exponential increase in 10−5 M Ach‐induced vasodilation as liver copper concentration increases from 0 μg Cu/g dry wt. This relationship suggests that dilation is attenuated at liver Cu concentrations below 5 μg/g dry wt. The results indicate that Ach‐induced vasodilation is copper‐dependent but that the pathway is not very sensitive to short‐term marginal restriction of copper intake.
The role of 4′‐phosphopantetheine in the biosynthesis of fatty acids, polyketides and peptides
Authors: Kleinkauf Horst
Published: December 2008

The peptide part of CoA, 4′‐phosphopantetheine, has been identified as an essential cofactor in in the biosynthesis of fatty acids, polyketides, depsipeptides, peptides, and compounds derived from both carboxylic and amino acid precursors, like rapamycin. The cofactor is attached to a unique protein moiety, referred to as acyl carrier protein, aminoacyl carrier protein, or peptidyl carrier protein. These carrier proteins are either associated to enzyme complexes (type II) or integrated within multifunctional polypeptide chains (type I). The cofactor is added in a post‐translational modification reaction by highly specific transferases, acting on CoA. The functions of carrier proteins in directed condensation reactions are: (1) the selection of substrates to be attached as thioesters, (2) the stabilization of intermediates, (3) the presentation of intermediates for modification by associated enyzme activities, (4) facilitation of the directed condensation reactions of two adjacent intermediates, and (5) assistance in the termination reaction(s) leading to product release.
Effect of dietary vitamin B6 contents on antibody production
Authors: Inubushi T. , Okada M. , Matsui A. , Hanba J. , Murata E. , Katunuma N.
Published: December 2008

When mice were placed on diets extreme deficient in vitamin B6, ovalbumin‐dependent antibody productions (IgE, IgG1, IgG2a) were significantly suppressed, and alanine aminotransferase activity in the liver was also significantly decreased.

In the case of pyridoxine excess (6 mg% = about ten times standard amount) in a 70% casein diet, ovalbumin‐dependent antibody productions were also considerably suppressed. These responses were weaker in a low casein (5%) or normal casein (20%) diet than in a 70% casein diet.

The administration of high doses of pyridoxine (6 mg%) resulted in the suppression of hepatic cathepsin B activity. Therefore, we conclude that ovalbumin‐dependent antibody productions (IgG1, IgE) were suppressed by pyridoxine excess diet (6 mg%), because hepatic cathepsin B activity was suppressed by the excess pyridoxine in diet.
Ecto‐diadenosine 5′,5‴‐P1,P4‐tetraphosphate (Ap4A)‐hydrolase is expressed as an ectoenzyme in a variety of mammalian and human cells and adds ne
Authors: Drygalski Annette Von , Ogilvie Adaling
Published: December 2008

Ap4A and other dinucleotides participate in the regulation of hemostasis and blood pressure control. With the exception of two previously reported surface anchored ectoAp4A‐hydrolases on bovine aortic endothelial and chromaffine cells, all Ap4A‐hydrolases reported are intracellular or freely soluble. We demonstrated that ectoAp4A‐hydrolases are present on a broad variety of cell types of different species: rat mesangial, bovine corneal epithelial, human Hep‐G2 and peridontal cells. Ectoenzyme properties were evaluated on rat mesangium cells. Chromatography of purified plasma membranes on Sephacel 300 resulted in enrichment of ectoAp4A‐hydrolase and in separation from ectoATPase. In contrast to ATPase, Ap4A‐hydrolase was stable at room temperature. EctoAp4A‐hydrolase also recognized ATP as substrate, and therefore is not highly specific. The molecular weight was 180 kD. Unlike ectoAMPase ectoAp4A‐hydrolase was not attached via a glycosyl‐phosphatidylinositol (GPI)‐moiety. Concentrations of PI‐PLC 10–100‐fold higher than effective for ectoAMPase cleavage (10–100 mU/ml) plus extensively extended incubation times up to eight hours did not result in cleavage of ectoAp4A‐hydrolase. The enzyme ectoAp4A‐hydrolase might presage a direction for pharmaceutical manipulation in the control of blood pressure and hemostasis.
Adenosine modulates cell growth in baby hamster kidney (BHK) cells
Authors: Mittal Rashmi A. , Tan Chee‐Hong , Khoo Hoon‐Eng
Published: December 2008

Adenosine is known to modulate cell growth in a variety of mammalian cells either via the activation of receptors or through metabolism. We investigated the effect of adenosine on Baby Hamster Kidney (BHK) cell growth and attempted to determine its mechanism of modulation. In wild‐type BHK cells, adenosine evoked a biphasic response in which a low concentration of adenosine (1± 150;5 μM) produced an inhibition of colony formation but at higher concentrations (up to 50 μM) this inhibition was progressively reversed. However, no biphasic response was observed in an ± 147;adenosine kinase± 148; deficient BHK mutant, ± 147;5a± 148;, which suggests that adenosine kinase plays an important role in the modulation of growth response to adenosine. Adenosine receptors did not appear to have a role in regulating cell growth of BHK cells. Specific A1and A2receptor antagonists were unable to reverse the effect of adenosine on cell growth. Even though a specific A3adenosine receptor antagonist MRS‐1220 partly reversed the inhibition in colony formation at 1 μM adenosine, it also affected the transport of adenosine. Thus adenosine transport and metabolism appears to play the major role in this modulation of cell growth as 5′‐amino‐5′‐deoxyadenosine, an adenosine kinase inhibitor, reversed the inhibition of cell growth observed at 1 μM adenosine. These results, taken together, would suggest that adenosine modulates cell growth in BHK mainly through its transport and metabolism to adenine nucleotides.
Functional food science in Japan: State of the art
Authors: Arai Soichi
Published: December 2008

In 1984, a new science related to functional food was initiated by a National Project team under the auspices of the Japan Ministry of Education and Science. It was followed by a great many academic and industrial studies to occupy a central position in the field of food and nutritional sciences. In 1993, the Ministry of Health and Welfare established a policy of “Foods for Specified Health Uses” (FOSHU) by which health claims of some selected functional foods are legally permitted. Up to now (November 22, 1999), 167 FOSHU products have been born. Since the time (1984) when the concept of “functional food” was proposed, it seems that the science in Japan has been progressing along, among others, a unique path of development. The uniqueness is seen in the development of functional foods by minimizing undesirable as well as maximizing desirable food factors. Hypoallergenic foods, developed from their materials by removing allergens, offer a good example. Another characteristic may be found in the field of sensory science which aims at elucidating a molecular logic of the senses of taste and smell in reference to their effects on physiological systems in the body. The paper discusses some characteristics of functional food science in Japan, with special emphasis on these topics.
Food system‐based approaches to improving micronutrient nutrition: The case for selenium
Authors: Combs Gerald F.
Published: December 2008

Micronutrient deficiencies affect nearly half the world's population, impairing child development, reducing work productivity, and increasing mortality and morbidity rates by affecting both infectious and chronic diseases. To feed a growing world, it will be necessary to consider agriculture in the broad context of a food system as an instrument of public health and, thus, to address nutrient balance while also seeking sustainability. Such efforts would include increasing cropping system diversity, enhancing micronutrient outputs and promoting environmental sustainability. Example of this approach are presented for the essential trace element selenium (Se), which at high intakes can reduce cancer risks but is deficient in many parts of the world. Food systems‐based approaches are discussed for preventing Se deficiency by enhancing intakes of any of several biologically available forms of Se, and for reducing cancer risk by enhancing intakes of forms of the element that support anti‐tumorigenic Se‐metabolites.
Role of diet modification in cancer prevention
Authors: Abdulla Mohamed , Gruber Per
Published: December 2008

Carcinogenesis encompasses a prolonged accumulation of injuries at several different biological levels and include both genetic and biochemical changes in the cells. At each of these levels, there are several possibilities of intervention in order to prevent, slow down or even halt the gradual march of healthy cells towards malignancy. Diet modification is one such possibility. A number of natural foodstuffs, especially fruits and vegetables contain substantial quantities of molecules that have chemopreventive potential against cancer development. Such compounds include vitamins, trace elements and a variety of other molecules with antioxidant properties. Carotenoids, flavanoid polyphenols, isoflavones, catechins, and several other components that found in cruciferous vegetables are molecules that are known to protect against the deleterious effect of reactive oxygen species. A number of epidemiological and experimental studies have shown that vitamin C and E, Beta‐carotene and the essential trace element selenium can reduce the risk of cancer. Consistent observations during the last few decades that cancer risk is reduced by a diet rich in vegetables, fruits, legumes, grains and green tea have encouraged research to identify several plant components especially phytochemicals that protect against DNA damage. Many of these substances block specific carcinogen pathways. Dietary supplements are part of an overall health program, along with a high intake of fruits and vegetables that help to combat damage to cells, which in turn may initiate cancer development. This paper will review current knowledge concerning diet modification and cancer prevention with special reference to minerals and trace elements.
High phosphorus feeding decreases the expression of renal PTH/PTHRP‐receptor mRNA in rats
Authors: Masuyama Ritsuko , Suzuki Kazuharu
Published: December 2008

Dietary intake of high phosphorus (P) is well‐described to increase serum levels of PTH, however, how this increased serum PTH affects the PTH actions in major target tissues, particularly in kidney, remains uncovered. We therefore undertook to clarify this point in intact animals fed the high‐P diet by examining various parameters of the PTH actions. Twelve weanling Wistar male rats were assigned randomly into the groups; a control group Ca:P=1:1 and a high‐P group (Ca:P=1:3) fed the standard AIN 76 diet supplemented with P (0.5 and 1.5 g/100 g diet). After 3 week feeding, in the high‐P diet group, we observed that serum Ca is lowered without difference in serum P when compared to those in the control group. Excretion of urine cAMP, an index of the renal PTH action, was also decreased with higher excretion of urine P by feeding the high P diet. In agreement with the decreased cAMP excretion, a clear reduction in the PTH/PTHrP receptor gene expression estimated by Northern blotting was observed in the kidney irrespective of increased levels of serum PTH. Thus, the present study indicated that high P dietary intake rather reduces the PTH actions in kidney though the serum PTH is increased.
Chemopreventive effects of coffee bean and rice constituents on colorectal carcinogenesis
Authors: Mori Hideki , Kawabata Kunihiro , Matsunaga Kengo , Ushida Jun , Fujii Keiko , Hara Akira , Tanaka Takuji , Murai Hiromichi
Published: December 2008

Polyphenolic compound chlorogenic acid (CGA) known to be much contained in coffee beans was found to have a regressive effect on induced aberrant crypt foci (ACF) as well as on development of ACF in azoxymethane (AOM)‐induced colorectal carcinogenesis in rats. Rice germ and γ‐aminobutyric acid‐enriched defatted rice germ inhibited AOM‐induced ACF formation and colorectal carcinogenesis in rats. Ferulic acid (FA) also known to be contained in coffee beans and rice prevented AOM‐induced ACF formation and intestinal carcinogenesis in rats. Both of food factors, coffee and rice may be of benefit to prevention of human colorectal cancers.
Role of antimutagens/anticarcinogens in cancer prevention
Authors: Shankel Delbert M. , Pillai S. P. , Telikepalli H. , Menon S. R. , Pillai C. A. , Mitscher L. A.
Published: December 2008

Recently it has become increasingly clear that chemicals found in our foods and beverages can prevent the genetic damage that leads to cancer initiation. Such substances may also affect subsequent events in the pathways that lead to cancer, and may have the potential to inhibit the mutations that allow tumor cells to become resistant to antitumor agents.

We describe here the antimutagenic potential of Glabrene analogs against EMS‐induced mutations utilizing modified Ames tests in it S. typhimurium TA 100 and E. coli JC 5088. Results of studies of the ability of well‐known antioxidants such as EGCG and related compounds to prevent drug resistance mutations in microorganisms are described, and their possible significance in the prevention of chemotherapeutic drug‐resistance in tumor cells is discussed.
Protein hydrolysates for oral tolerance
Authors: Lipkowski A. W. , Baranowska B. , Marczak E. , Kwiatkowska‐Patzer B. , Gajkowska B. , Walski M.
Published: December 2008

To induce oral tolerance in multiple sclerosis treatment, we proposed to use the predigested protein of pig spinal cord. The most biologically active composition was obtained from the hydrolysis of an undenaturated homogenate of proteins digested with pepsin. Feeding the rats with our preparation, before or after immunization with MS antigens, strongly reduced development of the experimental autoimmune encephalomyelitis (EAE). The biological results obtained in animals suggest that the developed method of induction of the oral tolerance should be effective in human treatment, at least as a support mechanism in combination with other treatment methods.
Metabolic fate of luteolin and its functional activity at focal site
Authors: Shimoi Kayoko , Saka Noriko , Kaji Kazuhiko , Kinae Ryushi Nozawa, Naohide
Published: December 2008

Luteolin has been shown to possess potent antioxidant and anti‐inflammatory/anti‐allergic activities. In order to evaluate a chemopreventive role of luteolin in inflammatory responses involved in the pathogenesis of atherosclerosis and cancer etc., the metabolic fate of luteolin in rats and humans was investigated by HPLC analysis, and its effect on cell surface expression of adhesion molecules in human umbilical vein endothelial cells(HUVECs) was examined by ELISA. Luteolin monoglucuronide, which was a main metabolite, and free luteolin were detected in rat plasma and human serum. Luteolin monoglucuronide was hydrolyzed to free luteolin by β‐glucuronidase released from neutrophils stimulated with Ionomycin and Cytocharasine B. Luteolin suppressed the TNF‐α induced ICAM‐1 expression significantly. Among nine flavonoids (40 μM) examined, chrysin, apigenine, quercetin and galangin also demonstrated suppressive effct on it. These results suggest the posssibility that deconjugation of luteolin monoglucuronide occurs and that free luteolin showed functional acyivities such as suppression of TNF‐α induced ICAM‐1 expression at inflammation site.
Antioxidant activity of soya hypocotyl tea in humans
Authors: Watanabe Shaw , Haba Ryota , Terashima Kayoko , Arai Yusuke , Miura Tsutomu , Chiba Hiroshige , Takamatsu Kiyoharu
Published: December 2008

Antioxidative activity of isoflavones has not been shown in humans. Newly‐developed isoflavone‐rich soya hypocotyl tea contains about 12 mg isoflavones per liter. 15 tea drinkers and 23 control young female students were randomly selected from volunteers, and underwent physical examination, blood chemistry and urinary analysis before and after one month of tea drinking. A three‐day dietary record was taken before each physical examination. The tea drinkers showed a lower level of phosphatidylcholine hydroperoxide (PCOOH) and phosphatidyl‐ethanolamine hydroperoxide (PEOOH) in the red blood cells and a significant reduction of 8‐hydroxydeoxyguanine (8ohdG) in the urine compared to the controls.
Effects of isoflavone supplement on healthy women
Authors: Watanabe Shaw , Terashima Kayo , Sato Yuho , Arai Sinsuke , Eboshida Akira
Published: December 2008

Effects of the isoflavone supplement on hormonal states in young premenopausal women were studied by cross‐over study design. Administration of 20 mg or 40 mg isoflavones (IF) by tablets, of which 1 g contained 43.5 mg daidzein, 6.0 mg genistein, 24.0 mg glycitein, to 40 young female students for one month caused a prolonged menstruation in 60% in 20% irregular. Larger dose tended to elongate more, but 17beta‐estradiol levels in both follicular and luteal phages were not different between 20 mg and 40 mg isoflavone intake. Equor excreters tended to show low plasma progesteron level in the luteal phase. Detailed hormonal analysis on 3 of students by a cross over study design showed decreased level of 17beta‐estradiol throughout the menstruation cycle. SHBG significantly increased about 10% androstendione, and testosterone showed different responses according to the follicular or luteal phase. T3 and T4 increased as a result of isoflavone tablet administration in the follicular phase, but it decreased in the luteal phase. These changes suggest that isoflavones influence not only estrogen receptor‐related functions but the hypothalamo‐hypophysis‐gonadal axis.
When is dietary fiber considered a functional food?
Authors: Prosky Leon
Published: December 2008

Before answering the question of when dietary fiber can be considered a functional food we must first decide what can be called a dietary fiber. The generally accepted definition of dietary fiber is that of Trowell that dietary fiber consists of the remnants of edible plant cells polysaccharides, lignin, and associated substances resistant to (hydrolysis) digestion by the alimentary enzymes of humans. In Japan the food tables list the dietary fiber content of animal as well as plant tissues, while many countries accept saccharides of less than DP‐10 as dietary fiber (inulin, oligofructose, Fibersol‐2, polydextrose, fructooligosaccharides, galactooligosaccharides etc.). These shorter chain oligosaccharides do not precipitate as dietary fiber in the standard Association of Official Analytical Chemists (AOAC) method, which is accepted by the US Food & Drug Administration, the US Department of Agriculture and the Food & Agriculture Organization of the World Health Organization for nutrition labeling purposes. In the United Kingdom the term dietary fiber has been replaced in nutrition labeling by nonstarch polysaccharides. Therefore the American Association of Cereal Chemists (AACC) commissioned an ad hoc committee of scientists to evaluate continuing validity of the currently used definition, and if appropriate, to modify and update that definition. Obtaining scientific input from the community of analysts, health professionals, and dietary fiber researchers was considered a high priority. To this end three meetings were held in the space of six months to assure input from all persons knowledgeable in the field with the answer expected sometime before 2000. Dietary fiber can be considered a functional food when it imparts a special function to that food aside from the normal expected function and similarly when the dietary fiber is used as an additive to foods. For example, dietary fiber contributes to colonic health, bifidobacterial or lactobacillus stimulation in the gut, coronary artery health, cholesterol reduction, glucose metabolism, insulin response, blood lipids, cancer etc. The author discusses in detail the functional food properties of dietary fiber.
Dietary docosahexaenoic acid does not promote tissue lipid peroxide formation to the extent expected from the peroxidizability index of the lipids
Authors: Saito Morio
Published: December 2008

Changes in susceptibility of tissues to lipid peroxidation were investigated in rats after ingestion of oxidation‐prone docosahexaenoic acid (C22:6n‐3). Lipid peroxide levels in the liver, kidney and testis increased concomitant with increases in the peroxidizability indices calculated from the fatty acid composition of tissue total lipids. However, even in these cases, the lipid peroxides were not increased to the levels expected from the peroxidizability indices of these tissues, and thus no tissue injury was recognized. When low level of vitamin∼E was given to rats, the lipid peroxide levels of liver, kidney and testis nearly coincided with the peroxidizability indices of these tissues, where the cell injuries were observed as well. The mechanisms of defense to suppress lipid peroxide levels below the peroxidizability indices in normal vitamin∼E administration were presumed to be due to enhanced antioxidative function in the tissues mediated primarily by vitamin E, ascorbic acid and glutathione, and also to increased incorporation of docosahexaenoic acid into neutral lipids and phosphatidylethanolamine in the tissues, probably leading to acquiring stability against oxidative attack. Owing to these suppressive mechanisms, physiological efficacy of n‐3 fatty acids may be exerted effectively.
Relationship between fatty acids and the endocrine system
Authors: Bhathena Sam J.
Published: December 2008

Significant interactions exist between fatty acids and the endocrine system. Hormones affect the metabolism of fatty acids and the fatty acid composition of tissue lipids. The principal hormones involved in lipid metabolism are insulin, glucagon, catecholamines, cortisol and growth hormone. The concentrations of these hormones are altered in chronic degenerative conditions such as diabetes and cardiovascular disease, which in turn lead to alterations in tissue lipids. Lipogenesis and lipolysis, which modulate fatty acid concentrations in plasma and tissues, are under hormonal control. Neuropeptides are involved in lipid metabolism in brain and other tissues. Polyunsaturated fatty acids (PUFA) are also precursors for eicosanoids including prostaglandins, leukotrienes, and thromboxanes, which have hormone‐like activities. Fatty acids in turn alter both hormone and neuropeptide concentrations and their receptors. Saturated and trans fatty acids (TFA) decrease insulin concentration leading to insulin resistance. In contrast, PUFA increase plasma insulin concentration and decrease insulin resistance. In humans, omega‐3 PUFA alter the levels of opioid peptides in plasma.
Chemoprevention of lung cancer by lycopene
Authors: Kim Dae Joong , Takasuka Nobuo , Nishino Hoyoku , Tsuda Hiroyuki
Published: December 2008

An investigation was conducted to assess the chemopreventive potential of lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and their products, administered during the post‐initiation stage in a multiorgan carcinogenesis model. One hundred eighteen B6C3F_1 mice of both sexes were subjected to combined treatment with diethylnitrosamine (DEN), N‐methyl‐N‐nitrosourea (MNU) and 1,2‐dimethylhydrazine (DMH) from day 11 after birth to week 9 (DMD treatment) (groups 1 and 2) or given their vehicles (group 3). Then group 1 received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32. Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or 50 ppm). The incidences and multiplicities of lung adenomas plus carcinomas combined in male mice in group 1 receiving LP 50 ppm were significantly decreased as compared to the DMD alone or DMD and LP 25 ppm group values (75.0 vs 18.8%, P < 0.02; 0.94 ± 0.17 vs 0.25 ± 0.14, P < 0.001). While hepatocellular carcinomas were lacking in the DMD and LP groups, two cases were found in the DMD alone group (not statistically significant). The values for aberrant crypt foci (ACF) and tumors in the colon and kidney did not show any significant variation among the carcinogen‐treated subgroups. The results of this study provide evidence that the tomato carotenoid, lycopene, may have potential as a chemopreventive agent against carcinogenesis in the male lung.
Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptors
Authors: Kawada Teruo , Kamei Yasutomi , Fujita Atsushi , Hida Yoshifumi , Takahashi Nobuyuki , Sugimoto Etsuro , Fushiki Tohru
Published: December 2008

The adipocyte differentiation program is regulated by the sequential expression of transcriptional activators, mainly peroxisome proliferator activated receptor (PPAR) families. In the present study, we have decided to systematically examine the effects of vitamin A and its precursors, carotenoids and retinoids, on terminal differentiation from preadipocytes to adipocytes on the cellular and molecular aspects. The effects of active form of vitamin A, retinoic acid (RA), are believed to be mediated by specific nuclear receptor proteins [retinoic acid receptor (RAR)] which are members of the steroid and thyroid/retinoid receptor superfamily of ligand dependent transcriptional regulators. RARα, RARγ, RXRα, and RXRβ mRNA were abundant in adipose tissue and 3T3‐L1 adipose cells. The autoregulated amplification of RARγ mRNA was observed by these own ligands in 3T3‐L1 cells. And, RA inhibited PPARγ2 expression more effectively and caused concomitantly a greater inhibition of adipocyte differentiation. These results suggest that the inhibitory action of adipocyte differentiation by carotenoids and retinoids are exhibited through the RAR up‐regulation and the suppression of PPARγ2. The nature of the cross talk of vitamin A actions between the RARs, RXRs and PPARs via co‐activator in adipose tissue will likely prove to be important for understanding the process of adipogenesis.
Phenolic antioxidants from herbs and spices
Authors: Nakatani Nobuji
Published: December 2008

Spices and herbs are recognized as sources of natural antioxidants and thus play an important role in the chemoprevention of diseases resulting from lipid peroxidation. Our studies on spices and herbs have given us over a hundred compounds, known and new, having high antioxidant activity. From the Labiatae family, Rosmarinus officinalis, Thymus vulgaris, Origanum vulgare and O. majorana gave 26 active comopounds. Over 40 antioxidative compounds from Zingiber officinale, 26 compounds from Curcuma domestica = C. longa, C. xanthorrhiza and Z. cassumunar were determined, these belonging to the family Zingiberaceae. From the family Myrtaceae, 25 compounds from the berries of Pimenta dioica were determined and 3 carbazoles were isolated from Murraya koenigii.

Structure‐activity relationships of some of the isolated compounds were also discussed.
Recent topics in anti‐oxidative factors
Authors: Yamada Koji , Tachibana Hirofumi
Published: December 2008

Lipids and anti‐oxidative factors regulate immune functions such as immunoglobulin production and chemical mediator release. For example, polyunsaturated fatty acids (PUFA) enhance IgE production of isolated rat lymphocytes, but not in the presence of α‐tocopherol. In addition, anti‐oxidative factors such as tea polyphenols and flavonoids exert inhibitory effect on chemical mediator release from rat peritoneal exudate cells (PEC). Some of these immunoregulatory activities of food components could be expressed in vivo. Oral administrations of perilla and fish oils or tea polyphenols led to a significant decrease of LTB_4 releasing activity of rat PEC, but IgE production enhancing activity of PUFA was not expressed in vivo. On the other hand, α‐tocopherol feeding enhanced serum IgA level as well as IgA productivity of mesenteric lymph node lymphocytes. These results suggest that dietary fats and antioxidants are effective for the alleviation of allergic symptom and activation of immune functions.
Antioxidative activities of aroma extracts isolated from natural plants
Authors: Lee Kwang‐Geun , Mitchell Alyson , Shibamoto Takayuki
Published: December 2008

Natural leaves and flowers containing numerous aroma chemicals are widely used in aromatherapy since ancient times. In addition to their pleasant smells, aroma chemicals might have some beneficial health effects. Aroma extracts, isolated from coffee beans, soybeans, and mung beans by steam distillation under mild conditions (55°C and 85 mm Hg) were examined for their antioxidative activities. The inhibitory effect of these extracts toward hexanal/hexanoic acid conversion was measured in the testing solution over prolonged time periods. The inhibitory effects of these extracts toward malonaldehyde formation from lipids oxidized by Fenton's reagent were also measured. The antioxidative activity of these extracts, in particular coffee bean extract, was consistent with that of BHT or α‐tocopherol (vitamin E). Soybeans and mung beans extract contained maltol, which inhibits hexanal oxidation significantly. Eugenol, which is one of the major constituents of mung bean extract, exhibited potent antioxidative activity in an aldehyde/carboxylic acid assay. Antioxidants such as eugenol and maltol may play an important role in the pharmaceutical activities of natural plant extracts used for aromatherapy.
The JaICA‐Genox Oxidative Stress Profile – An overview on the profiling technique in the oxidative stress assessment and management
Authors: Ochi Hirotomo , Cheng Rong‐Zhu , Kantha Sachi Sri , Takeuchi Masao , Ramarathnam Narasimhan
Published: December 2008

It is widely accepted that oxidative stress (OS) is a major causative factor for many of the age‐related dysfunctions and specific diseases. Since the oxidative stress state (OSS) of an individual depends on hereditary, dietary, and environmental factors, there is a large heterogeneity in the population that may be related to disease incidence and longevity. Hence there is a need to assess how well an individual is coping against OS. The Japan Institute for the Control of Aging (JaICA) and Genox have jointly developed a profiling technique to measure the “Oxidative Stress Profiles (JaICA‐Genox OSP)” of individuals and laboratory test animals. The JaICA‐Genox OSP consists of about 45 different assays measuring the levels of oxidative damage in lipids and nucleic acids, and the antioxidant defenses in the serum. In addition, several bio‐markers for cardiovascular disease risk are also measured, and assays to measure specific age‐ and sex‐related hormones in the serum and urine, and race elements in serum, urine, and drinking water are also undertaken. This overview discusses the designing of the JaICA‐Genox OSP and its application in the testing of human subjects.
Citrus limonoids obacunone and limonin inhibit azoxymethane‐induced colon carcinogenesis in rats
Authors: Tanaka Takuji , Kohno Hiroyuki , Tsukio Yoshiaki , Honjo Shiro , Tanino Mikio , Miyake Masaki , Wada Keiji
Published: December 2008

Obacunone and limonin are bitter limonoids in citrus. Their modifying effects on the development of aberrant crypt foci (ACF), the activity of detoxification enzymes, glutathione S‐transferase (GST) and quinone reductase (QR), and cell proliferation activity were investigated in male F344 rats treated with azoxymethane (AOM). Obacunone and limonin were administered in the diet, during the initiation (for 4 weeks) or postinitiation phase (for 4 weeks) of AOM‐induced tumorigenesis. Feeding of obacunone and limonin (0.02% or 0.05%) caused significant reduction (55–65% by “initiation” feeding and 28–42% by “postinitiation” feeding) in the yield of ACF. The ability to reduce the proliferating cell nuclear antigen‐labeling index in crypts and correlated well with the prevention of ACF. In a subsequent long‐term experiment (38 weeks), in which rats were initiated with AOM and fed 0.05% obacunone or 0.05% limonin during the initiation or post‐initiation phase, both compounds in diet caused significant reduction (65%–92% inhibition) in the incidence of colonic adenocarcinoma. Thus, citrus bitter limonoids obacunone and limonin possess chemopreventive effects on chemically induced rat colon carcinogenesis.
The role of triterpenoid on reactive oxygen scavenging system: Approach from the new chemiluminescence system (XYZ system)
Authors: Okubo Kazuyoshi , Yoshiki Yumiko
Published: December 2008

We propose that the reactive oxygen species/hydrogen donor/mediator system (XYZ system) is a new chemiluminescence system for the measurement of reactive oxygen scavenging activity. By using this method, we demonstrated the role of triterpenoid on a reactive oxygen scavenging system. DDMP (2,3‐dihydro‐2,5‐dihydroxy‐6‐methyl‐4H‐pyran‐4‐one) conjugated saponin from soybean, produced a low level light emission in the presence of H_2O_2 (X) and gallic acid (Y). The soybean saponin acted as a mediator (Z) on the reactive oxygen scavenging system. When comparing the data of photon emission properties of saponin with that of cholic acids, it concludes that DDMP moiety of soybean saponin plays an important role rather than the aglycon moiety in the radical scavenging system.
Functional properties of wasabi and horseradish
Authors: Kinae Naohide , Masuda Hideki , Shin Il Shik , Furugori Michiyo , Shimoi Kayoko
Published: December 2008

Wasabi (Wasabi japonica) and horseradish (Cholearia armoracia) are used as spices of daily foodstuffs. Allylisothiocyanate (AIT) is a potent component in both plants and occurs by grating them. It is well known that AIT shows inhibitory effect on the growth of food poisoning bacteria and fungi. In this work, several functional properties of roots and leaves from wasabi and horseradish were examined in vitro. Each sample showed peroxidase activity. They also exhibited antioxidative and superoxide scavenging potency. Antimutagenic activity was observed toward 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline [MeIQx], a well‐known mutagen/carcinogen in broiled fish and meat. They also decreased His+ revertant colonies of 3‐chloro‐4‐dichloromethyl‐5‐hydroxy‐2(5H)‐furanone (MX) in the Ames test, a strong mutagen and carcinogen in chlorine disinfected tap water. Isolation of antimutagenic components in wasabi root was done. Three components including (‐)‐(R)‐7‐methylsulfinylheptyl isothiocyanate were identified. These data show that wasabi and horseradish might be potent functional foods for keeping human health.
Antiplatelet and anticancer isothiocyanates in Japanese domestic horseradish, wasabi
Authors: Morimitsu Yasujiro , Hayashi Kazuhiro , Nakagawa Yoko , Horio Fumihiko , Uchida Koji , Osawa Toshihiko
Published: December 2008

6‐Methylsulfinylhexyl isothiocyanate (MS‐ITC) was isolated from wasabi (Wasabia japonica, Japanese domestic horseradish) as a potential inhibitor of human platelet aggregation in vitro through our extensive screening of vegetables and fruits. In the course of another screening for the induction of glutathione S‐transferase (GST) activity in RL34 cells, MS‐ITC was inadvertently isolated from wasabi as a potential inducer of GST. MS‐ITC administered to rats or mice also showed both activities in vivo. As a result from elucidation of the platelet aggregation inhibition and the GST induction mechanisms of MS‐ITC, the isothiocyanate moiety of MS‐ITC plays an important role for antiplatelet and anticancer activities because of its highly reactivity with sulfhydryl (‐SH) groups in biomolecules (GSH, cysteine residue in a certain protein, etc.).