bluuebunny/crossref_metadata_2025_split huggingface dataset:
Properties of fucoidan from Cladosiphon okamuranus tokida in gastric mucosal protection
Authors: Shibata Hideyuki , Kimura‐Takagi Itsuko , Nagaoka Masato , Hashimoto Shusuke , Aiyama Ritsuo , Iha Masahiko , Ueyama Sadao , Yokokura Teruo 
Published: December 2008

AbstractTo elucidate the anti‐ulcer potential of Cladosiphon fucoidan, anti‐peptic activity, bFGF stabilizing activity and inflammatory properties of this and related substances were investigated. Anti‐peptic activity was observed with this and other sulfated polysaccharides such as dextran sulfate, carrageenan, and Fucus fucoidan. However, non‐sulfated polysaccharides such as mannan and dextran did not exert the anti‐peptic activity. The loss of bFGF bioactivity was prevented by all sulfated polysaccharides tested except chondroitin sulfate, at pH 7.4 and at pH 4.0. At pH 2.0, only heparin protected the bFGF activity. The generation of superoxide by macrophages and PMNs was stimulated by dextran sulfate, carrageenan, and Fucus fucoidan, whereas Cladosiphon fucoidan, heparin and chondroitin did not. Dextran sulfate, carrageenan, and Fucus fucoidan also stimulated the secretion of TNFα from macrophages, while Cladosiphon fucoidan did not. Thus, Cladosiphon fucoidan is a sulfated polysaccharide without inflammatory action. These results suggest that Cladosiphon fucoidan is a safe substance with potential for gastric protection.
Inhibition of angiotensin‐converting enzyme protects endothelial cell against hypoxia/reoxygenation injury
Authors: Fujita Noriko , Manabe Hiroki , Yoshida Norimasa , Matsumoto Naohito , Ochiai Jun , Masui Yasuharu , Uemura Manabu , Naito Yuji , Yoshikawa Toshikazu 
Published: December 2008

AbstractCardiovascular tissue injury in ischemia/reperfusion has been shown to be prevented by angiotensin‐converting enzyme (ACE) inhibitors. However, the mechanism on endothelial cells has not been assessed in detail. Cultured human aortic endothelial cells (HAEC) were exposed to hypoxia with or without reoxygenation. Hypoxia enhanced apoptosis along with the activation of caspase‐3. Reoxygenation increased lactate dehydrogenase release time‐dependently, along with an increase of intracellular oxygen radicals. ACE inhibitor quinaprilat and bradykinin significantly lessened apoptosis and lactate dehydrogenase release with these effects being diminished by a kinin B2 receptor antagonist and a nitric oxide synthase inhibitor. In conclusion, hypoxia activated the suicide pathway leading to apoptosis of HAEC by enhancing caspase‐3 activity, while subsequent reoxygenation induced necrosis by enhancing oxygen radical production. Quinaprilat could ameliorate both apoptosis and necrosis through the upregulation of constitutive endothelial nitric oxide synthase via an increase of bradykinin, with the resulting increase of nitric oxide.
Prevention of cancer and other chronic diseases worldwide based on sound mechanisms
Authors: Weisburger John H. 
Published: December 2008

AbstractThe transformation of normal cells by DNA reactive, genotoxic carcinogens and the growth promotion and development of mutated cells by enhancing factors is involved in the overall basic mechanism of cancer induction. Thus, discrimination between genotoxic carcinogens and nongenotoxic chemicals is essential. The dose‐response curves, reversibility, and organ‐and species specificity are distinct. Genotoxic carcinogens are mutagenic, form DNA adducts, induce DNA repair, and form hydroxy radicals and inappropriate peroxidation reactions that antioxidants such as those in vegetables, fruits, and tea can decrease. In contrast, promoters do not form DNA adducts, but raise cell duplication rates, among other attributes. In the USA, about 35% about 55% decreased by avoiding the formation of carcinogens, reducing their metabolic activation, or increasing their detoxification. Excessive dietary salt, and heterocyclic arylamines formed in cooking of meats or fish, and high intake of 40% vegetables, fruits, tea, soy products, and fibers are protective. We review nutritional factors involved in cancer and chronic disease causation and prevention.
Bioactive peptides derived from food proteins preventing lifestyle‐related diseases
Authors: Yoshikawa Masaaki , Fujita Hiroyuki , Matoba Nobuyuki , Takenaka Yasuyuki , Yamamoto Taichi , Yamauchi Rena , Tsuruki Hirotaka , Takahata Kyoya 
Published: December 2008

AbstractMany kinds of bioactive peptides which might prevent lifestyle‐related diseases are released from food proteins after enzymatic digestion. Inhibitory peptides for angiotensin I‐converting enzyme (ACE) having anti‐hypertensive effect have been isolated from enzymatic digests of various food proteins. LKPNM, which was isolated from the thermolysin digest of dried bonito was activated 8‐fold by ACE itself and showed a prolonged effect after oral administration. Two vasorelaxing peptides, ovokinin and ovokinin(2–7), showing antihypertensive effect after oral administration were obtained from ovalbumin digests. We found that low molecular weight peptides derived from food proteins lowered serum cholesterol without increasing excretion of cholesterol and bile acids. An immunostimulating peptide isolated from an enzymatic digest of soybean protein prevented alopecia induced by cancer chemotherapy.
Anticancer activity of hydrophobic peptides from soy proteins
Authors: Kim Song E , Kim Hyuck Hwa , Kim Ji Yeon , Kang Young Im , Woo Hee Jong , Lee Hyong Joo 
Published: December 2008

AbstractAn anticancer peptide from soy protein was purified and isolated. Defatted soy protein was hydrolyzed with thermoase and hydrophobic peptides were extracted with ethanol. The peptide extract was fractionated by XAD‐2 hydrophobic, gel filtration chromatography, and different C18 HPLCs. Anticancer activity of each fraction was assayed by measuring in vitro cytotoxicity on P388D1, a mouse monocyte macrophage cell line. IC50 value of a peptide fraction from Sephadex G‐25 chromatography was 0.16 mg/ml. This peptide fraction at 1 mg/ml significantly affected cell cycle progression by arresting P388D1 at G2/M phases. Finally purified peptide from analytical C18 HPLC was nonapeptide of which molecular weight was 1157 Da and the sequence was X‐Met‐Leu‐Pro‐Ser‐Tye‐Ser‐Pro‐Tyr.
Respective bioavailability of quercetin aglycone and its glycosides in a rat model
Authors: Morand Christine , Manach Claudine , Crespy Vanessa , Remesy Christian 
Published: December 2008

AbstractA large number of flavonoids, mostly O‐glycosides, are found in foods of plant origin. The bound sugar moiety is known to influence their bioavailability. We examined here the effect of the nature of the sugar on the absorption of the glycosides. Four groups of rats (n=6) received a meal containing 20 mg of quercetin equivalents supplied as aglycone, quercetin 3‐glucoside, quercetin 3‐rhamnoside or rutin. Plasma were hydrolysed by a βglucuronidase/sulfatase and analyzed by HPLC coupled to UV detection at 370 nm. Four hours after the beginning of the meal, the quercetin metabolites present in plasma were identical in all groups but their total concentrations were quite different. With pure quercetin the circulating levels were 11.7± 1.8 μM, but this level was three fold higher when quercetin was supplied as quercetin 3‐glucoside (33.2± 3.5 μM). By contrast, the plasma concentrations of quercetin metabolites was quite low with the rutin meal (about 3 μM) and undetectable after the quercetin 3‐rhamnoside meal. These data suggest that the 3‐O‐glucosylation improves the absorption of quercetin in the small intestine, whereas the binding of a rhamnose or of a glucose‐rhamnose moiety to the aglycone markedly depressed its absorption. Additionnal experiments have shown that the higher plasma levels measured after the meal containing quercetin 3‐glucoside compared to quercetin were maintained throughout a 24 hour period following the meal.In conclusion, the nature of the glycosylation markedly influences the efficiency of quercetin absorption in rats. Quercetin 3‐glucose can be absorbed in the small intestine and is better absorbed than quercetin itself. By contrast, glycosides containing a rhamnose moiety could not be absorbed in the small intestine.
Suppressive effects of citrus fruits on free radical generation and nobiletin, an anti‐inflammatory polymethoxyflavonoid
Authors: Murakami Akira , Nakamura Yoshimasa , Ohto Yoshimi , Yano Masamichi , Koshiba Teruaki , Koshimizu Koichi , Tokuda Harukuni , Nishino Hoyoku , Ohigashi Hajime 
Published: December 2008

AbstractCitrus fruit intake is known to be associated with a reduction of cancer incidence. Free radicals, including superoxide (O−2) and nitric oxide (NO), are involved in some epithelial carcinogenesis processes. In the present study, we screened thirty‐one citrus fruits for their suppressive activities toward three lines of free radical generating systems: 1) O−2 generation by the xanthine (XA)‐xanthine oxidase (XOD) system; 2) O−2 generation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in differentiated human promyelocytic HL‐60 cells; and 3) NO generation in murine macrophage RAW264.7 cells stimulated with lipopolysaccharide (LPS) and interferon (IFN)‐γ. As a result, the inhibitory activities of peel parts were largely found to be higher than those of the corresponding juice sac parts. In particular, the peel portion of Dancy tangerine (Citrus tangerina) showed marked anti‐oxidative activities in these systems. In addition, nobiletin, a polymethoxyflavonoid isolated from C. nobilis, showed a higher anti‐inflammatory activity than indomethacin in a TPA‐induced edema formation test in mouse ears. These results indicate that citrus fruits could be notable sources of anti‐oxidative, anti‐inflammatory, and cancer preventive compounds.
Mechanisms involved in the chemoprevention of flavonoids
Authors: Siess Marie‐HÉLÉNe , Bon Anne‐Marie Le , Canivenc‐Lavier Marie‐Chantal , Suschetet Marc 
Published: December 2008

AbstractFlavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin were investigated on two steps of aflatoxin B1 (AFB1)‐induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of γ‐glutamyl transpeptidase‐preneoplastic foci. In the same conditions of administration, quercetin, a polyhydroxylated flavonoid, showed no protective effect. Moreover, feeding rats with flavanone during the phenobarbital‐induced promotion step significantly reduced the areas of placental glutathione S‐transferase preneoplastic foci. Quercetin, flavone, and tangeretin, administered in the same conditions, caused no significant effect. Therefore flavanone act as an anti‐initiator as well as an anti‐promotor. Several mechanisms were involved in the anti‐initiating effects of flavone, flavanone, and tangeretin: enhancement of enzymes involved in the detoxication of AFB1 (glutathione S‐transferase, UDP‐glucuronyl transferase), increase of the formation of AFB1‐glutathione conjugates and inhibition of the binding of AFB1 to DNA. Although the relevance of these data to the human situation remains to be demonstrated, they confirm that several flavonoids administered by the dietary route possess promising chemoprotective effects.
Isoflavonoids and chronic disease: Mechanisms of action
Authors: Barnes S. , Boersma B. , Patel R. , Kirk M. , Darley‐Usmar V. M. , Kim H. , Xu J. 
Published: December 2008

AbstractSoy and its isoflavones are associated with a reduced risk of chronic disease. The mechanisms of action of isoflavones include their roles as weak estrogens, inhibitors of tyrosine kinase‐dependent signal transduction processes and as cellular antioxidants. Although estrogen receptor beta binds genistein with an affinity close to that of 17β‐estradiol, it remains to be determined whether it is a mediator of genistein's activity in vivo. Genistein's inhibition of protein tyrosine kinases is not limited to direct effect on these kinases, but may result from alteration in kinase expression. Genistein is not a particularly good scavanger of cellular oxidants; however, it reacts vigorously with the prooxidant hypochlorous acid, produced by neutrophils as part of the inflammatory response. The chlorinated isoflavones may have altered biochemical and biological effects compared to their parent compounds and may provide increased protection against inflammatory disease.
Comparison of plasma and urinary phytoestrogens in Japanese and Finnish women by time‐resolved fluoroimmunoassay
Authors: Uehara Mariko , Arai Yusuke , Watanabe Shaw , Adlercreutz Herman 
Published: December 2008

AbstractTime‐resolved fluoroimmunoassays (TR‐FIA), with europium labeled phytoestrogens as tracers, were developed for the quantitative measurement of genistein, daidzein and enterolactone in plasma and urine for the purpose of screening large populations and studies on possible correlation between the values in biological fluids and the risk of western diseases.The mean values of the three phytoestrogens in plasma as determined by TR‐FIA were similar to those obtained by gas chromatography‐mass spectrometry (GC‐MS). The urinary excretion levels of total individual phytoestrogens were higher than those obtained by GC‐MS, with the exception of the daidzein values. However, comparing the assay results obtained by the present method and those obtained by GC‐MS, a strong correlation was evident (r=0.87‐0.99, p<0.001).We measured plasma levels of genistein, daidzein and enterolactone in 111 healthy Japanese women. The mean and median levels of genistein were 406.8 and 306.3 nmol/l, respectively, and those of daidzein were 118.4 and 76.8 nmol/l, respectively. These levels are higher than those reported for Americans and Western Europeans. Isoflavone intake as calculated from dietary records (genistein: mean, 86.5 μmol/day and daidzein: mean, 57.4 μmol/day) was correlated with the plasma concentrations observed (genistein: r=0.287, p<0.01 and daidzein: r=0.313, p<0.01). Plasma enterolactone levels were low in Japanese women (mean, about 10 nmol/l). The levels of urinary excretions of genistein, daidzein were also measured and it was found that, in the majority, the levels ranged between 5–25 and 5–50 μmol/24 h, respectively. In contrast, healthy Finnish women showed very low values of isoflavones (below 10nmol/l in plasma (n=87) and below 0.6 μmol/24h in urine (n=126) for both compounds) and high levels of enterolactone in both plasma and urine (plasma: mean, 25nmol/l and urine: majority range, 1–7 μmol/24 h).
Attenuation of neurodegeneration‐relevant modifications of brain proteins by dietary soy
Authors: Kim Helen , Xia Hongli , Li Lin , Gewin John 
Published: December 2008

AbstractEpidemiological studies show that postmenopausal women who undertake estrogen‐replacement therapy have significantly lower risk for the onset of Alzheimer's disease (AD) than women who do not. Animal behavior studies have shown that ovariectomy results in the development of cognitive dysfunction that is prevented by estrogen‐replacement, suggesting that normal mammalian cognitive function is impaired by estrogen reduction. Soy isoflavones in particular genistein have been demonstrated to have weak and selective estrogenic actions in various models of human chronic diseases. A hallmark of several human dementias including AD and fronto temporal dementia with Parkinsonism on chromosome 17 (FTDP‐17) is the hyperphosphorylation of the microtubule‐associated protein tau. Preliminary experiments are discussed here which show that isoflavones delivered in a soy protein matrix attenuated selected AD‐relevant tau phosphorylations in a primate model of menopause. The rationale is discussed for the use of soy‐based foods for protection against postmenopausal neurodegeneration.
Anti‐tumor polysaccharides from mushrooms during storage
Authors: Mizuno Masashi 
Published: December 2008

AbstractThe changes in the contents of an anti‐tumor polysaccharide from Lentinus edodes (lentinan) and Grifola frondosa (GGF) during storage were investigated using by an ELISA inhibition assay. When the mushrooms were stored at low temperature, the contents of their anti‐tumor polysaccharides show hardly any changes, but their contents decreased markedly at higher temperature (20°C). Moreover, the effect of the extract from Lentinus edodes stored at different temperatures on tumor necrosis factor (TNF)‐α and nitric oxide (NO) productions from macrophages was investigated to confirm the influence to the stimulation of macrophages. Because lentinan stimulates macrophages to augment their antitumor activity. Their productions showed little difference between Lentinus edodes stored at low temperature and the fresh mushroom, although the cytokine production decreased significantly in Lentinus edodes stored at 20°C. These results suggest that low‐temperature storage is more effective in maintaining not only the quality of the mushrooms but also the contents of anti‐tumor polysaccharides as health‐beneficient foods.
Butyrate as a model for “Gene‐regulating chemoprevention and chemotherapy”
Authors: Sowa Yoshihiro , Sakai Toshiyuki 
Published: December 2008

AbstractRecent progress in molecular genetics has facilitated understanding of the mechanisms of carcinogenesis. However, there is not yet any effective therapy or prevention for cancer based on the molecular mechanisms of carcinogenesis. So‐called “gene therapy” for cancer is expected to become a new method of treatment, but there are still several serious problems with gene therapy. As a matter of fact, it seems impossible to adopt gene therapy for prevention. We therefore tried to develop a different method of cancer prevention or therapy based on the molecular mechanisms of carcinogenesis. For instance, the tumor‐suppressor gene p53 is mutated in about 50% malignancies. It is known that p53 stimulates the promoter activities of p21/WAF1, gadd45 and bax genes, resulting in cell cycle arrest, DNA repair and apoptosis, respectively. Therefore, chemical compounds that can stimulate these genes should compensate for the function of p53. As a model of this, we found that histone deacetylase inhibitors such as butyrate or trichostatin A dramatically stimulate the p21/WAF1 gene promoter through the Sp1 sites, resulting in cell cycle arrest. Interestingly, another group has recently reported that phenylbutyrate, which is also known as a histone deacetylase inhibitor, is very effective for leukemia patients. We therefore consider methods of up‐regulating p21/WAF, gadd45 or bax genes should be useful for cancer therapy and termed this method “Gene‐regulating chemotherapy”. Theoretically, the chemicals up‐regulating such genes should be also useful for chemoprevention, and we also termed it as “Gene‐regulating chemoprevention”.In conclusion, we propose that “Gene‐regulating chemotherapy or chemoprevention” may be a promising new method for cancer therapy or prevention and histone deacetylase inhibitor is a good candidate for this method.
Effect of dietary α‐linolenic acid on the activity and gene expression of hepatic fatty acid oxidation enzymes
Authors: Ide Takashi 
Published: December 2008

AbstractThe activities of hepatic fatty acid oxidation enzymes in rats fed linseed and perilla oils rich in α‐linolenic acid (α‐18:3) were compared with those in the animals fed safflower oil rich in linoleic acid (18:2) and saturated fats (coconut or palm oil). Mitochondrial and peroxisomal palmitoyl‐CoA (16:0‐CoA) oxidation rates in the liver homogenates were significantly higher in rats fed linseed and perilla oils than in those fed saturated fats and safflower oil. The fatty oxidation rates increased as dietary levels of α‐18:3 increased. Dietary α‐18:3 also increased the activity of fatty acid oxidation enzymes except for 3‐hydroxyacyl‐CoA dehydrogenase. Unexpectedly, dietary α‐18:3 caused great reduction in the activity of 3‐hydroxyacyl‐CoA dehydrogenase measured with short‐ and medium‐chain substrates but not with long‐chain substrate. Dietary α‐18:3 significantly increased the mRNA levels of hepatic fatty acid oxidation enzymes including carnitine palmitoyltransferase I and II, mitochondrial trifunctional protein, acyl‐CoA oxidase, peroxisomal bifunctional protein, mitochondrial and peroxisomal 3‐ketoacyl‐CoA thiolases, 2, 4‐dienoyl‐CoA reductase and Δ3, Δ2‐enoyl‐CoA isomerase. Fish oil rich in very long‐chain n‐3 fatty acids caused similar changes in hepatic fatty acid oxidation. Regarding the substrate specificity of β‐oxidation pathway, mitochondrial and peroxisomal β‐oxidation rate of α‐18:3‐CoA, relative to 16:0‐ and 18:2‐CoAs, was higher irrespective of the substrate/albumin ratios in the assay mixture or dietary fat sources. The substrate specificity of carnitine palmitoyltransferase I appeared to be responsible for the differential mitochondrial oxidation rates of these acyl‐CoA substrates. Dietary fats rich in α‐18:3‐CoA relative to safflower oil did not affect the hepatic activity of fatty acid synthase and glucose 6‐phosphate dehydrogenase. It was suggested that both substrate specificities and alterations in the activities of the enzymes in β‐oxidation pathway play a significant role in the regulation of the serum lipid concentrations in rats fed α‐18:3.
Platelet‐activating factor (PAF)‐like oxidized phospholipids: Relevance to atherosclerosis
Authors: Tokumura Akira , Sumida Tuneki , Toujima Masaoki , Kogure Kentaro , Fukuzawa Kenji 
Published: December 2008

AbstractLipid peroxidation is involved in the pathogenesis of chronic diseases including atherosclerosis. Oxidized lipoprotein has diverse biological activities and is believed to initiate atheroma formation and maturate fatty plaque. The active components of oxidized lipoproteins still remain to be clarified, but a likely candidate is the phosphatidylcholine (PC) having an it sn‐2‐short‐chain acyl group with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs, formed by oxidative fragmentation of the polyunsaturated acyl group of the parent PC in liposomes, low density lipoproteins and blood plasma, induce platelet aggregation through the activation of the receptor for platelet‐activating factor (PAF), due to their resemblance in structure with PAF. We have found that PAF‐like lipids regulate DNA synthesis and production of nitric oxide independently of the activation of the PAF receptor in vascular smooth muscle cells. Regulation of vascular cell function through two distinct signaling pathways mediated by PAF‐like lipids provides new insight into the mechanism of induction of atherosclerosis.