Biomedical subjects

Yoshinobu Kiso

Publications and source records attributed to Yoshinobu Kiso.

At least 19 recordsLinked to original sources

PubMed2006

Anti-tumor activities of the antlered form of Ganoderma lucidum in allogeneic and syngeneic tumor-bearing mice.

We investigated the anti-tumor effects of a dry powder preparation of the antlered form of Ganoderma lucidum (G. lucidum AF, rokkaku-reishi in Japanese), a variant type of G. lucidum, not only in allogeneic Sarcoma 180-bearing ddY mice, but also in syngeneic MM 46-bearing C3H/He mice. G. lucidum AF inhibited tumor growth and elongated the life span when orally administered to mice by free-feeding of a 2.5% G. lucidum AF-containing diet. It also showed anti-tumor activity in spite of post-feeding after tumor inoculation. G. lucidum AF significantly countered the depression of splenic CD8+ cells and protected the decrease in interferon-gamma (IFN-gamma) production in regional lymph nodes of MM 46-bearing mice, indicating that the anti-tumor activity of G. lucidum AF might be caused by its immunostimulating action. These results suggest that the ingestion of G. lucidum AF can be useful for the prevention and curing of cancer.

Animals↗

PubMed2006

Distribution and metabolism of dihomo-gamma-linolenic acid (DGLA, 20:3n-6) by oral supplementation in rats.

We compared the dietary effects of dihomo-gamma-linolenic acid (DGLA) contained in the DGLA oil produced by a fungus with gamma-linolenic acid (GLA) on the fatty acid composition. Wistar rats were fed with three kinds of oil for two weeks as follows: (i) control group: corn oil; (ii) GLA group: borage oil; (iii) DGLA group: DGLA oil/safflower oil = 55:45. The DGLA concentrations in the liver, serum, and brain of the DGLA group were higher than those of the GLA oil group. We also examined the dose effect of DGLA. The DGLA levels in the liver, serum, and brain significantly increased with increasing dosage of DGLA in the diet. DGLA administration significantly increased the ratio of PGE1/PGE2 in the rat plasma. The mechanism for GLA administration to improve atopic eczema is thought to involve an increase in the concentration of DGLA metabolized from GLA, so these results suggest that the dietary effect of DGLA would be more dominant than GLA.

8,11,14-Eicosatrienoic Acid↗

PubMed2006

Selectivity of fatty acid ligands for PPARalpha which correlates both with binding to cis-element and DNA binding-independent transactivity in Caco-2 cells.

It is thought that peroxisome proliferator-activated receptor alpha (PPARalpha) is a major regulator for fatty acid metabolism. Long-chain fatty acids have been shown to induce expression of the genes related to fatty acid metabolism through PPARalpha. However, it is unclear whether the intensity of PPARalpha activation is different among various fatty acids. In this study, we compared various fatty acids in the capability of PPARalpha activation by differential protease sensitivity assay (DPSA), electrophoretic mobility shift assay and GAL4-PPAR chimera reporter assay in intestinal cell line, Caco-2. DPSA revealed that polyunsaturated fatty acids of 18 to 20 carbon groups with 3-5 double bonds strongly induced a PPARalpha conformational change. The ligand-induced changes in the sensitivity to protease corresponded to the enhancement of the binding of PPARalpha-RXRalpha heterodimer to the PPAR-response element (PPRE). The GAL4-PPAR chimera reporter assay revealed that the DNA binding-independent transactivity of PPARalpha was induced by various fatty acids with a wide spectrum of intensity which correlated with the conformational change of PPARalpha. These results suggest that PPARalpha has greater selectivity to certain types of polyunsaturated fatty acids, and that the ligand-induced conformational change of PPARalpha leads to parallel increases in both DNA binding to the PPAR-response element and the DNA binding-independent transactivity.

Binding, Competitive↗

PubMed2006

Renoprotective effects of l-carnosine on ischemia/reperfusion-induced renal injury in rats.

We examined the renoprotective effects of l-carnosine (beta-alanyl-l-histidine) on ischemia/reperfusion (I/R)-induced acute renal failure (ARF) in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. In vehicle (0.9% saline)-treated rats, renal sympathetic nerve activity (RSNA) was significantly augmented during the renal ischemia, and renal function was markedly decreased at 24 h after reperfusion. Intracerebroventricular injection of l-carnosine (1.5 and 5 pmol/rat) to ischemic ARF rats dose-dependently suppressed the augmented RSNA during ischemia and the renal injury at 24 h after reperfusion. N-alpha-Acetyl-l-carnosine [N-acetyl-beta-alanyl-l-histidine; 5 pmol/rat intracerebroventricular (i.c.v.)], which is resistant to enzymatic hydrolysis by carnosinase, did not affect the renal injury, and l-histidine (5 pmol/rat i.c.v.), a metabolite cleaved from l-carnosine by carnosinase, ameliorated the I/R-induced renal injury. Furthermore, a selective histamine H(3) receptor antagonist, thioperamide (30 nmol/rat i.c.v.) eliminated the preventing effects by l-carnosine (15 nmol/rat intravenously) on ischemic ARF. In contrast, a selective H(3) receptor agonist, R-alpha-methylhistamine (5 pmol/rat i.c.v.), prevented the I/R-induced renal injury as well as l-carnosine (5 pmol/rat) did. These results indicate that l-carnosine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppressing the enhanced RSNA during ischemia. In addition, the present findings suggest that the renoprotective effect of l-carnosine on ischemic ARF is induced by its conversion to l-histidine and l-histamine and is mediated through the activation of histamine H(3) receptors in the central nervous system.

Acute Kidney Injury↗

PubMed2006

Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction.

Age-dependent increase of peroxidation of membrane fatty acids such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) in neurons was reported to cause a decline of the hippocampal long-term potentiation (LTP) and cognitive dysfunction in rodents. Although supplementation of ARA and DHA can improve LTP and cognitive function in rodents, their effects in humans are unknown. The present work was undertaken to study whether ARA and DHA have beneficial effects in human amnesic patients. The subjects were 21 mild cognitive dysfunction (12 MCI-A with supplementation and 9 MIC-P with placebo), 10 organic brain lesions (organic), and 8 Alzheimer's disease (AD). The cognitive functions were evaluated using Japanese version of repeatable battery for assessment of neuropsychological status (RBANS) at two time points: before and 90 days after the supplementation of 240 mg/day ARA and DHA, or 240 mg/day of olive oil, respectively. MCI-A group showed a significant improvement of the immediate memory and attention score. In addition, organic group showed a significant improvement of immediate and delayed memories. However, there were no significant improvements of each score in AD and MCI-P groups. It is suggested from these data that ARA and DHA supplementation can improve the cognitive dysfunction due to organic brain damages or aging.

Adult↗

PubMed2006

Evaluation of the hypolipemic property of Camellia sinensisVar. ptilophylla on postprandial hypertriglyceridemia.

A naturally decaffeinated tea, Camellia sinensis var. ptilophylla (cocoa tea), has long been popular in southern China as a healthy beverage. Our experiments indicate that a single oral administration of 500 mg/kg of cocoa tea extract suppresses increases in plasma triacylgycerol (TG) levels when fed with 5 mL/kg of olive or lard oil in mice and that the inhibition rates are 22.9% and 31.5%, respectively, compared with controls. Under the same condition, cocoa tea extract did not affect the level of plasma free fatty acid. Likewise, the extract reduced the lymphatic absorption of lipids at 250 and 500 mg/kg. Also, cocoa tea extract and polyphenols isolated from cocoa tea inhibit pancreatic lipase. These findings suggest that cocoa tea has hypolipemic activity, which may be due to the suppression of digestive lipase activity by the polyphenols contained within the tea.

Animals↗

PubMed2006

Arachidonic acid preserves hippocampal neuron membrane fluidity in senescent rats.

Previous studies indicate that long-term dietary supplementation with arachidonic acid (AA) in 20-month-old rats (OA) effectively restores performance in a memory task and the induction of long-term potentiation in the hippocampus to the level of young control animals (YC). The present study examined protein mobility using the live cell imaging technique "Fluorescent Recovery After Photobleaching (FRAP)" in YC, old control (OC) and OA neurons in hippocampal slice preparations. Three measures; mobile fraction (M(f)), diffusion constant (D) and time constant (tau), were estimated among YC, OC and OA. Each of these parameters was significantly different between OC and YC, suggesting that membrane fluidity is lower in OC than in YC. In contrast, D and tau were comparable in OA and YC, indicating that hippocampal neuronal membranes supplemented with AA were more fluid than those in OC, whereas the fraction of diffusible protein in the bleached region remained smaller than in YC. Long-term administration of AA to senescent rats might help to preserve membrane fluidity and maintain hippocampal plasticity.

Aging↗

PubMed2006

Effects of beer and hop on ionotropic gamma-aminobutyric acid receptors.

Beer induced the response of the ionotropic gamma-aminobutyric acid receptors (GABA(A) receptors) expressed in Xenopus oocytes, indicating the presence of gamma-aminobutyric acid (GABA)-like activity. Furthermore, the pentane extract of the beer, hop (Humulus lupulus L.) oil, and myrcenol potentiated the GABA(A) receptor response elicited by GABA. The GABA(A) receptor responses were also potentiated by the addition of aliphatic esters, most of which are reported to be present in beer flavor. Aliphatic esters showed the tendency to decrease in the potentiation of the GABA(A) receptor response with an increase in their carbon chain length. When myrcenol was injected to mice prior to intraperitoneal administration of pentobarbital, the pentobarbital-induced sleeping time of mice increased additionally. Therefore, the beer contained not only GABA-like activity but also the modulator(s) of the GABA(A) receptor response.

Acyclic Monoterpenes↗

PubMed2006

Sesamin metabolites induce an endothelial nitric oxide-dependent vasorelaxation through their antioxidative property-independent mechanisms: possible involvement of the metabolites in the antihypertensive effect of sesamin.

Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radical-scavenging activities against the xanthine/xanthine oxidase-induced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m- and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (NOARG), or a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Neither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NOARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin.

Animals↗

PubMed2006

Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene.

Brain-type fatty acid-binding protein (B-FABP) belongs to a family of intracellular lipid-binding proteins. B-FABP exhibits a binding affinity to long-chain fatty acids (FAs) whose effects on brain functions including development, emotion, learning and memory have been proposed. B-FABP is localized in the ventricular germinal cells in embryonic brain and astrocytes in developing and mature brain of rodents. In the present study we generated the mouse harboring a null mutation in the B-FABP gene and studied its phenotype. B-FABP mutant mice exhibited the enhanced anxiety and increased fear memory as well as the decreased content of docosahexaenoic acid (DHA) in their brain during the neonatal period without detection of any histological changes in the brain. In the adult brain, B-FABP was localized more numerously to the astrocytes in the amygdala and septal area than to those in the hippocampal area. Analysis of FA content in the amygdala of adult brain revealed that arachidonic and palmitic acids increased significantly in the mutant mice compared with wild-type. Furthermore, the response of N-methyl-d-aspartate receptor-mediated current to DHA in isolated neurons from B-FABP mutant brain was significantly decreased compared with that of wild-type, while no significant differences were detected in behavioral responses related to the spatial learning/memory or in the hippocampal long-term potentiation. These data indicate that B-FABP is crucially involved in the fear memory and anxiety through its binding with FAs and/or its own direct effects on pertinent metabolism/signaling of FAs.

Animals↗

PubMed2006

Antihypertensive effect of angiotensin I-converting enzyme inhibitory peptides from a sesame protein hydrolysate in spontaneously hypertensive rats.

Sesame peptide powder (SPP) exhibited angiotensin I-converting enzyme (ACE) inhibitory activity, and significantly and temporarily decreased the systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) by a single administration (1 and 10 mg/kg). Six peptide ACE inhibitors were isolated and identified from SPP. The representative peptides, Leu-Val-Tyr, Leu-Gln-Pro and Leu-Lys-Tyr, could competitively inhibit ACE activity at respective Ki values of 0.92 microM, 0.50 microM, and 0.48 microM. A reconstituted sesame peptide mixture of Leu-Ser-Ala, Leu-Gln-Pro, Leu-Lys-Tyr, Ile-Val-Tyr, Val-Ile-Tyr, Leu-Val-Tyr, and Met-Leu-Pro-Ala-Tyr according to their content ratio in SPP showed a strong antihypertensive effect on SHR at doses of 3.63 and 36.3 microg/kg, which accounted for more than 70% of the corresponding dosage for the SPP-induced hypotensive effect. Repeated oral administration of SPP also lowered both SBP and the aortic ACE activity in SHR. These results demonstrate that SPP would be a beneficial ingredient for preventing and providing therapy against hypertension and its related diseases.

Administration, Oral↗

PubMed2005

Inhibitory effects of oolong tea polyphenols on pancreatic lipase in vitro.

Fifty-four polyphenols isolated from tea leaves were evaluated for their inhibitory activities against pancreatic lipase, the key enzyme of lipid absorption in the gut. (-)-Epigallocatechin 3-O-gallate (EGCG), which is one of major polyphenols in green tea, showed lipase inhibition with an IC50 of 0.349 microM. Moreover, flavan-3-ol digallate esters, such as (-)-epigallocatechin-3,5-digallate, showed higher activities of inhibition on lipase with an IC50 of 0.098 microM. On the other hand, nonesterified flavan-3-ols, such as (+)-catechin, (-)-epicatechin, (+)-gallocatechin, and (-)-epigallocatechin, showed zero and/or the lowest activities against pancreatic lipase (IC50 > 20 microM). These data suggested that the presence of galloyl moieties within the structure was required for enhancement of pancreatic lipase inhibition. It is well-known that flavan-3-ols are polymerized by polyphenol oxidase and/or heating in a manufacturing process of oolong tea. Oolonghomobisflavans A and B and oolongtheanin 3'-O-gallate, which are typical in oolong tea leaves, showed strong inhibitory activities with IC50 values of 0.048, 0.108, and 0.068 microM, respectively, even higher than that of EGCG. The oolong tea polymerized polyphenols (OTPP) were prepared for the assay from oolong tea extract, from which the preparation effectively subtracted the zero and/or less-active monomeric flavan-3-ols by preparative high-performance liquid chromatography. The weight-average molecular weight (Mw) and number-average molecular-weight (Mn) values of OTPP were 2017 and 903, respectively, by using gel permeation choromatography. OTPP showed a 5-fold stronger inhibition against pancreatic lipase (IC50 = 0.28 microg/mL) by comparison with that of the tannase-treated OTPP (IC50 = 1.38 microg/mL). These data suggested that the presence of galloyl moieties within their chemical structures and/or the polymerization of flavan-3-ols were required for enhancement of pancreatic lipase inhibition.

Camellia sinensis↗

PubMed2005

Arachidonic acid improves aged rats' spatial cognition.

To examine the effects of arachidonic acid (AA) on age-related cognitive deficits, F-344 rats were administered with an AA-supplemented powder diet from 79 weeks of age (OA group). For comparison, we also used an age-matched control group of animals (OC group) that were fed with a non AA-supplemented powder diet. When the subjects reached 87 weeks old, they were trained for Morris water maze place and cue tasks. Escape latencies of the OA group on the place task were significantly shorter than those of the OC group in the latter half of training. The probe test showed that OA rats remembered the trained platform position significantly better than OC rats. In the cue task training, the OC group was significantly slower than the OA group at the beginning of training, but their performance soon matched with that of the OA group. Fatty acids in the hippocampi were measured after the behavioral testing. There was no difference in AA composition in hippocampal phospholipids between the OA and OC groups. However, regression analysis conducted on AA composition and place task performance showed a significant correlation between these two parameters. The present study suggests that AA administration to aged animals can alleviate age-related deficits in spatial cognition.

Aging↗

PubMed2005

Sesamin ingestion regulates the transcription levels of hepatic metabolizing enzymes for alcohol and lipids in rats.

BACKGROUND: Sesamin, a major lignan in sesame seeds, has multiple functions such as stimulation effect of ethanol metabolism in mice and human, and prevention of ethanol-induced fatty liver in rats. However, the mechanism has not been clarified yet. METHODS: The changes of gene expression were investigated in rats given 250 mg/kg of sesamin (sesamin rats) or vehicle (control rats) for three days by using a DNA microarray analysis. At 4 hr after the final ingestion, the profiles of gene expression in rat livers were compared. RESULTS: The analysis showed that 38 transcripts were up-regulated with a significant change of more than two-fold and eight transcripts were down-regulated with a significant change to less than half in the livers of sesamin rats versus control rats. The gene expression levels of the early stage enzymes of beta-oxidation including long-chain acyl-CoA synthetase, very long-chain acyl-CoA synthetase and carnitine palmitoyltransferase were not changed, however, those of the late stage enzymes of beta-oxidation including trifunctional enzyme in mitochondria, and acyl-CoA oxidase, bifunctional enzyme and 3-ketoacyl-CoA thiolase in peroxisomes, were significantly increased by sesamin ingestion. Also, in sesamin rats, the gene expression of aldehyde dehydrogenase was increased about three-fold, whereas alcohol dehydrogenase, liver catalase and CYP2E1 were not changed. Changes in the gene expression of alcohol- and aldehyde-metabolizing enzymes observed in a DNA microarray were also confirmed by a real-time PCR method. CONCLUSIONS: These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for alcohol and lipids.

Aldehyde Dehydrogenase↗

PubMed2005

Influence of low dietary histamine on seizure development of chemical kindling induced by pentylenetetrazol in rats.

AIM: To determine the role of dietary low histamine on the seizure development of pentylenetetrazol (PTZ)-induced kindling in rats. METHODS: After 14 d of feeding on a low histamine diet (LH, containing 0.145 mumol/g of histamine), the rats were chemically kindled by repeated intraperitoneal injection of a subconvulsant dose of PTZ (35 mg/kg) once every 48 h, and seizure activity of kindling was recorded for 30 min. Histamine in brain samples was analyzed using a high performance liquid chromatography system with a fluorescence spectrofluorometer. RESULTS: The LH diet induced an increase in seizure response (seizure susceptibility) to the first trial of PTZ, and resulted in facilitation of subsequent PTZ kindling process (seizure development). The histamine levels in the cortex, hippocampus, and hypothalamus of LH-treated rats decreased significantly and these changes correlated well with seizure behavior (r = 0.875, 0.651, and 0.796, respectively). In addition, chronic kindled seizures resulted in a significant increase of the histamine content in the cortex and hypothalamus in the LH-fed groups. CONCLUSION: These findings indicate that the histamine in daily food could influence the brain histaminergic function, and play an important role in regulating seizure susceptibility.

Animals↗

PubMed2005

Preventive effect of flavangenol on ischemia/reperfusion-induced acute renal failure in rats.

The effects of flavangenol on ischemia/reperfusion-induced acute renal failure (ARF) in rats were examined. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured. Renal function in ARF rats markedly decreased at 1 d after reperfusion. Pre-ischemic treatment with flavangenol (3-30 mg/kg, i.v.) attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damage, such as tubular necrosis and proteinaceous casts in tubuli, which were also significantly suppressed by the administration of flavangenol. These findings suggest that flavangenol supplementation may be a promising candidate for treatments to improve the ischemia/reperfusion-induced renal injury.

Acute Kidney Injury↗

PubMed2005

Dietary supplementation of L-carnosine prevents ischemia/reperfusion-induced renal injury in rats.

The effects of dietary supplementation of L-carnosine (beta-alanyl-L-histidine) on ischemia/reperfusion-induced acute renal failure (ARF) in rats were examined. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured. Renal function in ARF rats markedly decreased at 1 d after reperfusion. Prior feeding of L-carnosine-containing diet (0.0001 w/w%) for 2 weeks attenuated the ischemia/reperfusion-induced renal dysfunction. Histopathological examination of the kidney of ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, which were also significantly suppressed by the dietary supplementation of L-carnosine. These findings strongly suggest that L-carnosine supplementation is useful as a prophylactic treatment in the development of the ischemic ARF.

Animals↗

PubMed2005

Modulating effect of sesamin, a functional lignan in sesame seeds, on the transcription levels of lipid- and alcohol-metabolizing enzymes in rat liver: a DNA microarray study.

Sesamin, a major lignan in sesame seeds, has multiple functions such as cholesterol-lowering and anti-hypertensive activities. To investigate the effect of sesamin on gene expression in the liver, a DNA microarray analysis was carried out. The ingestion of sesamin dissolved in olive oil up-regulated the expression of 38 genes, 16 of which encode proteins possessing a lipid-metabolizing function, and 16 of which encode proteins possessing a xenobiotic/endogenous substance metabolizing function. In particular, sesamin significantly increased the expression of beta-oxidation-associated enzymes in peroxisomes and auxiliary enzymes required for degradation, via the beta-oxidation pathway, of unsaturated fatty acids in mitochondria. The ingestion of sesamin also resulted in an increase in the gene expression of acyl-CoA thioesterase involved in acyl-CoA hydrolase and very-long-chain acyl-CoA thioesterase. Interestingly, it induced the expression of the gene for aldehyde dehydrogenase, an alcohol-metabolizing enzyme. These results suggest that sesamin regulates the metabolism of lipids, xenobiotics, and alcohol at the mRNA level.

Alcohols↗