Protective effect of UV-irradiated red perilla (Perilla frutescens (L.) Britton) on carbon tetrachloride-induced liver injury in mice.

UV-irradiated red perilla demonstrated promising protective effects against carbon tetrachloride-induced liver injury in mice. UV exposure significantly enhanced the accumulation of rosmarinic acid, malonylshisonin, and shisonin in red perilla, and increased 1,1-diphenyl-2-picrylhydrazyl radical scavenging capacity. The hepatoprotective effect of UV-irradiated red perilla may be attributed to the high level of its polyphenolic compounds, which exhibit antioxidant activity.

Erucic Acid-Rich Yellow Mustard Oil Improves Insulin Resistance in KK-Ay Mice.

Obesity is a major risk factor for some metabolic disorders including type 2 diabetes. Enhancement of peroxisome proliferator-activated receptor (PPAR) γ, a master regulator of adipocyte differentiation, is known to increase insulin-sensitive small adipocytes. In contrast, decreased PPARγ activity is also reported to improve insulin resistance. We have previously identified erucic acid as a novel natural component suppressing PPARγ transcriptional activity. In this study, we investigated the effect of erucic acid-rich yellow mustard oil (YMO) on obese/diabetic KK-Ay mice. An in vitro luciferase reporter assay and mesenchymal stem cell (MSC) differentiation assay revealed that 25 µg/mL YMO significantly inhibited PPARγ transcriptional activity and differentiation of MSCs into adipocytes but promoted their differentiation into osteoblasts. In KK-Ay mice, dietary intake of 7.0% (w/w) YMO significantly decreased the surrogate indexes for insulin resistance and the infiltration of macrophages into adipose tissue. Furthermore, 7.0% YMO increased bone mineral density. These results suggest that YMO can ameliorate obesity-induced metabolic disorders.

Effect of mushroom polysaccharides from Pleurotus eryngii on obesity and gut microbiota in mice fed a high-fat diet.

PURPOSE: Mushrooms are reported to have a variety of health-promoting activities. However, little information is available on the effects of intake of polysaccharides from Pleurotus eryngii on obesity. In this study, we investigated the effects of P. eryngii polysaccharides on obesity and gut microbiota in mice fed a high-fat diet. METHODS: Soluble polysaccharides were extracted from P. eryngii using hot water. C57BL/6J mice were fed a standard diet (ST), a high-fat diet (HF), or HF with 1% or 5% P. eryngii polysaccharide fraction (LP or HP) for 16 weeks. Adipose tissues were weighed and blood parameters were measured. Expression of genes involved in fatty acid and cholesterol metabolism was assessed by real-time quantitative PCR. The gut microbiota composition was analysed by 16S rRNA gene sequencing. RESULTS: Body weight gain and mesenteric fat tissue were lower in the HP group than in the HF group. In the HP group, serum total cholesterol and LDL cholesterol levels decreased, and lipid and total bile acids in faeces increased. Mice in the HP group showed increased expression of the LDLR gene in the liver and GPR43 in fat. The relative abundance of Firmicutes was significantly higher in the HF and HP groups than in the ST group. The abundance of some short-chain fatty acid-producing gut bacteria was altered by P. eryngii polysaccharides. CONCLUSIONS: These results provide the first evidence that P. eryngii polysaccharides have anti-obesity and LDL cholesterol-lowering effects in obese mice through increased excretion of bile acids and lipids and altered microbiota.

Erucic acid derived from rosemary regulates differentiation of mesenchymal stem cells into osteoblasts/adipocytes via suppression of peroxisome proliferator-activated receptor γ transcriptional activity.

Osteoporosis is associated with increase in fat tissue in bone marrow in humans. Mesenchymal stem cells in bone marrow are induced to differentiate into osteoblasts rather than adipocytes by the stimulation of peroxisome proliferator-activated receptor (PPAR) γ antagonists. PPARγ antagonists are expected to be useful to prevent osteoporosis by regulating the lineages of mesenchymal stem cells in bone marrow, as well as the prevention of obesity. In this study, we explored natural components suppressing PPARγ transcriptional activity in rosemary. Separation of active fraction of rosemary extract by repeated high performance liquid chromatograph and PPARγ luciferase reporter assay identified erucic acid, one of the monounsaturated fatty acids, as an active component. Twenty-five-micrometer erucic acid significantly decreased PPARγ luciferase activity and enhanced the differentiation of mouse-delivered C3H10T1/2 cells into osteoblasts rather than adipocytes. Furthermore, 25-µM erucic acid significantly decreased the expression of adipocyte marker genes, while accelerating osteoblast marker genes. In conclusion, erucic acid is a novel natural component derived from rosemary regulating mesenchymal stem cell differentiation via suppression of PPARγ transcriptional activity.

PGC1α regulates ACMSD expression through cooperation with HNF4α.

ACMSD is a tryptophan metabolic key enzyme. HNF4α regulates the transcription of some energy-metabolic enzymes by cooperating with PGC1α, a major transcriptional co-regulator involved in energy metabolism. In this study, we investigated the involvement of PGC1α in Acmsd expression through cooperation with HNF4α. Luciferase reporter assay was performed in NIH3T3 cells using a reporter vector containing HNF4α responsive elements in the Acmsd 5' upstream transcriptional regulatory region together with HNF4α and/or PGC1α expression vectors. The Acmsd luciferase reporter activity was greatly elevated by co-overexpression of HNF4α and PGC1α in NIH3T3 cells. Moreover, the expression level of Acmsd mRNA was significantly increased by co-overexpression of HNF4α and PGC1α in primary hepatocytes compared with expression of either HNF4α or PGC1α alone. These results indicate that PGC1α is involved in Acmsd expression through cooperation with HNF4α.

Ferulic acid suppresses expression of tryptophan metabolic key enzyme indoleamine 2, 3-dioxygenase via NFκB and p38 MAPK in lipopolysaccharide-stimulated microglial cells.

Ferulic acid (FA) is a phenol compound found in plants that has anti-inflammatory properties. Indoleamine 2, 3-dioxygenase (IDO) is a tryptophan catabolic enzyme induced in immune cells, including glial cells, during inflammation. Enhanced IDO expression leads to reduced tryptophan levels and increased levels of toxic metabolites, including quinolinic acid. Therefore, inhibition of IDO expression may be effective in suppressing progression of neurodegenerative diseases. In this study, we examined the effect of FA in microglial cells on IDO expression levels and related inflammatory signal molecules. FA suppressed LPS-induced IDO mRNA expression and also suppressed nuclear translocation of NF-κB and phosphorylation of p38 MAPK. However, FA did not affect the production of LPS-induced inflammatory mediators and phosphorylation of JNK. Our results indicate that FA suppresses LPS-induced IDO mRNA expression, which may be mediated by inhibition of the NF-κB and p38 MAPK pathways in microglial cells.

Regulation of rat hepatic α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase, a key enzyme in the tryptophan- NAD pathway, by dietary cholesterol and sterol regulatory element-binding protein-2.

PURPOSE: Nicotinic acid is one of the older drugs used to treat hyperlipidemia, the greatest risk factor of coronary heart disease. Nicotinic acid is also a precursor of the coenzyme nicotinamide adenine dinucleotide (NAD). In mammals, α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays a key role in NAD biosynthesis from tryptophan. However, the relationship between ACMSD and cholesterol metabolism has not been clarified enough yet. The present study was performed to make clear the relationship between ACMSD and cholesterol metabolism using hypercholesterolemic rats and rat primary hepatocytes. METHODS: Male Sprague-Dawley rats were fed a diet containing cholesterol for 10 days to induce hypercholesterolemia. The NAD levels in the plasma and liver and hepatic ACMSD activity were determined. In vitro study, the expression of ACMSD and the transcriptional factors that regulate cholesterol metabolism were determined using rat primary hepatocytes treated with cholesterol and 25-hydroxycholesterol or simvastatin, a statin medication, by quantitative real-time PCR analysis and Western blotting analysis. RESULTS: The hepatic NAD level of the hypercholesterolemic group was significantly higher than the control, and the hepatic ACMSD activity of this group was significantly suppressed. There was a significant negative correlation between the hepatic ACMSD activity and liver cholesterol levels. Additionally, in primary rat hepatocytes treated with cholesterol and 25-hydroxycholesterol or simvastatin, ACMSD gene and protein expression was subjected to sterol-dependent regulation. This gene expression changed in parallel to sterol regulatory element-binding protein (SREBP)-2 expression. CONCLUSION: These results provide the first evidence that ACMSD is associated with cholesterol metabolism, and ACMSD gene expression may be upregulated by SREBP-2.

Gene expression analysis of the liver and skeletal muscle of psyllium-treated mice.

Psyllium, a dietary fibre rich in soluble components, has both cholesterol- and TAG-lowering effects. Many studies have verified these actions using liver samples, whereas little information is available on the effects of psyllium treatment on other organs. The purpose of the present study was to evaluate the possible beneficial effects of psyllium. We investigated the gene expression profiles of both liver and skeletal muscle using DNA microarrays. C57BL/6J mice were fed a low-fat diet (LFD; 7 % fat), a high-fat diet (HFD; 40 % fat) or a HFD with psyllium (40 % fat+5 % psyllium; HFD+Psy) for 10 weeks. Body weights and food intake were measured weekly. After 10 weeks, the mice were killed and tissues were collected. Adipose tissues were weighed, and plasma total cholesterol and TAG blood glucose levels were measured. The expression levels of genes involved in glycolysis, gluconeogenesis, glucose transport and fatty acid metabolism were measured by DNA microarray in the liver and skeletal muscle. In the HFD+Psy group, plasma total cholesterol, TAG and blood glucose levels significantly decreased. There was a significant reduction in the relative weight of the epididymal and retroperitoneal fat tissue depots in mice fed the HFD+Psy. The expression levels of genes involved in fatty acid oxidation and lipid transport were significantly up-regulated in the skeletal muscle of the HFD+Psy group. This result suggests that psyllium stimulates lipid transport and fatty acid oxidation in the muscle. In conclusion, the present study demonstrates that psyllium can promote lipid consumption in the skeletal muscle; and this effect would create a slightly insufficient glucose state in the liver.

Effect of dietary phytol on the expression of α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase, a key enzyme of tryptophan-niacin metabolism, in rats.

α-Amino-ß-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays a key role in the regulation of NAD biosynthesis or the production of quinolinate from tryptophan (Trp). We investigated in this study the effect of phytol, a phytochemical known as a peroxisome proliferator-activated receptor α (PPARα) ligand, on NAD synthesis and ACMSD expression in rats. Male Sprague-Dawley rats were fed a diet containing 0.5%, 1%, or 2% phytol for 7 d. Phytol decreased the ACMSD activity and its mRNA expression in a dose-dependent manner in the liver. Phytol similarly and significantly suppressed ACMSD mRNA expression in primary rat hepatocytes. However, the mRNA expression of ACO (a known PPARα target gene) was higher in the low-phytol groups than in the high-phytol group in vivo and in vitro. Phytol increased the blood NAD level by suppressing ACMSD mRNA expression in the liver of the rats. It is possible that this mechanism occurred by the activation of PPARα and also of other transcriptional factors.

Effect of apigenin on tryptophan metabolic key enzymes expression in lipopolysaccharide-induced microglial cells and its mechanism.

[Aims] Flavonoid apigenin (API) has a wide range of biological functions, particularly anti-inflammation. Indoleamine 2,3-dioxygenase (IDO) and 2-Amino-3-carboxymuconate-6-semialdehyde decarboxylase (ACMSD) are important tryptophan metabolic enzymes that play pivotal roles in the production of toxic metabolite quinolinic acid. However, the relationship between inflammation and ACMSD remains unclear. The present study investigated the relationship between inflammation and tryptophan metabolic key enzymes. Similarly, the anti-inflammatory effect of API on important tryptophan metabolic enzymes was examined in lipopolysaccharide (LPS)-treated microglial cells. [Main methods] MG6 cells were exposed to LPS with or without API treatment for 24-48 h. IDO and ACMSD mRNA expression and production of inflammatory mediators were analyzed. Activation of inflammatory signaling pathways, such as mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB), was also examined to study the mechanism of API in the inflammatory state. [Key findings] LPS suppressed ACMSD expression and enhanced IDO expression. However, API elevated ACMSD mRNA expression and suppressed IDO mRNA expression in LPS-treated MG6 cells. Furthermore, API suppressed interleukin-6 and nitric oxide production, whereas overproduction of inflammatory mediators enhanced IDO expression and assisted tryptophan degradation. API also inhibited activation of extracellular signal-regulated kinase (Erk) and jun N-terminal kinase (JNK) MAPK, and degradation of IκBα. [Significance] These results indicate alteration of ACMSD expression under inflammatory conditions. Moreover, API recovers expression of tryptophan metabolic key enzymes, which may be mediated by inhibition of proinflammatory mediator production via inactivation of Erk, JNK MAPK, and NF-κB pathways in LPS-stimulated microglial cells.

Suppressive effect of modified arabinoxylan from rice bran (MGN-3) on D-galactosamine-induced IL-18 expression and hepatitis in rats.

We investigated in this study the effect of modified arabinoxylan from rice bran (MGN-3) and its fractions on D-galactosamine (D-GalN)-induced IL-18 expression and hepatitis in rats. Male Wistar rats were pretreated with MGN-3 or fractions of the MGN-3 hydrolysate, or with saline 1 h before administering D-GalN (400 mg/kg B.W.). The serum transaminase activities, IL-18 mRNA expression level in the liver and IL-18 concentration in the serum were determined 24 h after injecting D-GalN. Both the oral and intraperitoneal administration of MGN-3 (20 mg/kg B.W.) alleviated D-GalN-induced hepatic injury under these experimental conditions. The low-molecular-weight fraction (LMW) of MGN-3 showed the strongest protective effect on D-GalN-induced liver injury, its main sugar component being glucose. Moreover, the D-GalN-induced IL-18 expression was significantly reduced by treating with MGN-3 and LMW. The results suggest that MGN-3 and LMW could provide significant protection against D-GalN liver injury, and that IL-18 might be involved in their protective influence.

Protection by dietary Spirulina platensis against D-galactosamine--and acetaminophen-induced liver injuries.

Increasing attention has been paid to Spirulina for its potential clinical uses. The present study investigated the protection by dietary Spirulina platensis against d-galactosamine (d-GalN)- and acetaminophen (APAP)-induced hepatitis in ICR mice. Mice in each group (n 6) were fed with a standard diet (American Institute of Nutrition (AIN)-93G), a positive control diet containing 0.5 % butylated hydroxytoluene (BHT), or a diet containing 3, 6 or 9 % S. platensis for 1 week. On the last day the mice were treated with d-GalN (300 mg/kg body weight, intraperitoneally) or APAP (150 mg/kg body weight, intraperitoneally) and 24 h later the mice were killed. The doses of both 6 and 9 % S. platensis were found to significantly alleviate the increase of serum glutamate oxaloacetoacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities in d-GalN- or APAP-intoxicated mice. The observation was very similar to that of the positive control groups. Two more experiments were carried out to investigate the involvement of thiobarbituric acid-reactive substances (TBARS) and IL-18 in the suppression of 6 % S. platensis on d-GalN- and APAP-induced hepatitis. The significant increase of GOT and GPT activities was found to be accompanied with the elevation of hepatic TBARS level, IL-18 mRNA expression and serum IL-18 concentration, and was significantly alleviated by supplementation with 6 % S. platensis in diets. These results showed that dietary S. platensis could provide a significant protection against d-GalN- and APAP-induced liver injuries, and IL-18 and lipid peroxidation might be involved in the protective influence of S. platensis.

Mechanism of the suppression against D-galactosamine-induced hepatic injury by dietary amino acids in rats.

To elucidate the mechanism by which dietary amino acids suppress the D-galactosamine (D-GalN)-induced hepatitis, we examined the involvement of Kupffer cells, tumor necrosis factor-alpha (TNF-alpha) and apoptosis in the mechanism. In experiment 1, the rats were fed with 10% L-glutamine or 5% glycine diet injected with D-GalN with or without gadolinium chloride (GdCl3)-pretreatment. The results indicated that these amino acids suppressed the D-GalN-induced elevation of serum transaminase activities, irrespective of GdCl3-pretreatment. In experiment 2, rats were fed with 10% of L-glutamine, L-serine, L-alanine or L-glutamic acid diets injected with D-GalN. The results demonstrated that all these amino acids suppressed the D-GalN-induced elevation of serum transaminase activities, but that serum TNF-alpha concentrations and hepatic caspase-3 activities in the rats were not appreciably changed. In conclusion, the suppressive effects of amino acids on D-GalN-induced hepatitis were suggested not to be always mediated by the inhibition of Kupffer cells --> TNF-alpha --> apoptosis pathway.

Production of L-tryptophan-derived catabolites in hepatocytes from streptozotocin-induced diabetic rats.

BACKGROUND: Recently the L-tryptophan (Trp) metabolites such as L-kynurenine(Kyn), L-kinurenic acid, quinolinic acid (QA) and picolinic acid (PA) have been shown physiologically important in central nervous and immune system, and various enzyme activities concerning their production were reported to be affected by insulin-dependent diabetes mellitus. However, the states of these metabolites in diabetes have not been clarified enough yet. AIM OF STUDY: The present study was performed to make clear the states of the productions of L-Kyn, QA, PA and nicotinamide (Nam) in vitro in the hepatocytes prepared from streptozotocin (STZ)-induced diabetic rats using [5-3H]L-Trp. METHODS: The diabetic model rats were made by STZ injection (60 mg/kg) and the hepatocytes isolated from the rats were incubated with [5-3H]L-Trp. The amounts of metabolites derived from L-Trp were determined by the isotope-dilution methods. RESULTS: The alpha-amino-beta-carboxymuconate-epsilon-semiarldehyde decarboxylase (ACMSD) mRNA level in the diabetic group was greatly higher than that in the control group. In the STZ-induced diabetes group, the amount of [5-3H]L-Trp converted to tritiated water, L-Kyn or QA were found to be more than 3 times of that in the control group, respectively. The produced amounts of PA and Nam were not significantly different between the diabetic and the control groups. CONCLUSIONS: It is suggested that STZ-diabetes mellitus causes augmentations of both L-Kyn and QA generations but not those of PA and Nam in liver, indicating the possibility that the immune and neuronal systems of insulin dependent diabetes mellitus would be influenced by the increased amounts of LKyn and QA but not by those of PA and Nam.

The Combination of 'Benifuuki' with Quercetin Suppresses Hepatic Fat Accumulation in High-Fat High-Cholesterol Diet-Fed Rats.

We investigated the combined effects of 'Benifuuki,' a tea cultivar that contains O-methylated catechins like epigallocatechin-3-O-(3-O-methyl) gallate, and quercetin on hepatic fat accumulation in male Sprague-Dawley rats fed a high-fat, high-cholesterol diet for 15 d. Rats given 'Benifuuki'+quercetin had synergistically lower liver triglyceride (TG) level compared with rats given 'Benifuuki' or quercetin alone. Compared with 'Benifuuki' or quercetin alone, supplementation with 'Benifuuki'+quercetin resulted in a low level of fatty acid synthase (FAS) and stearoyl-CoA desaturase1 (SCD1) gene expression levels. These results suggest that the combination of 'Benifuuki' and quercetin has greater liver lipid-lowing effects than that of 'Benifuuki' or quercetin alone. The liver TG-lowing effect of combination of 'Benifuuki' with quercetin may be partially mediated by the suppression of lipogenesis. The combination of 'Benifuuki' and quercetin suppresses hepatic fat accumulation in high fat high cholesterol diet fed rats, showing a new trend of 'Benifuuki' as synergist with quercetin.

L-Gln and L-Ser suppress the D-galactosamine-induced IL-18 expression and hepatitis.

D-Galactosamine (GalN) induces acute hepatitis in experimental animals and this hepatitis has been shown to be suppressed by preceding ingestion of amino acids such as Gly, L-Ser, and L-Gln. However, little is known about the mechanism of its action. The present study shows for the first time that IL-18 reduction is involved in the suppressive actions of L-Gln and L-Ser on GalN-induced hepatitis. Elevation of IL-18 mRNA expression in liver and its concentration in serum in GalN-treated rats were found to be suppressed by preceding ingestion of 10% L-Gln- or 10% L-Ser diets, and resulted in the attenuation of the increase in serum transaminase (ALT and AST) activities, indexes of hepatic injury. These results suggest that suppressive effects of some dietary amino acids on the GalN-induced hepatitis are mediated by IL-18 reduction.

Effects of resistant maltodextrin on bowel movements: a systematic review and meta-analysis.

It is well known that dietary fiber helps to relieve and prevent constipation, and there are a number of scientific papers, including systematic reviews and meta-analyses on the effects of naturally derived dietary fiber on bowel movements. In recent years, there has been an increase in the manufacture of dietary fiber ingredients obtained from food raw materials, and these are now commonly available in the market. Resistant maltodextrin (RMD), a soluble dietary fiber, is manufactured from starch, and industrially produced soluble dietary fiber is used worldwide. While there are many reports on the effects of RMD on bowel movements, no systematic review or meta-analysis has been reported. We conducted a systematic review and meta-analysis to clarify the effect of RMD on bowel movements based on stool frequency and stool volume. We also investigated the subjective evaluation of RMD effects on bowel movements. Of a total of 314 potentially relevant articles, 28 articles met the eligibility criteria, and 29 randomized controlled trials were identified. As a result of integration analyses, we found that the intake of RMD significantly increased stool volume and stool frequency compared with placebo intake. Furthermore, RMD intake tended to improve sensation of complete/incomplete evacuation. In conclusion, the evidence suggests that RMD has a positive effect on bowel movements, contributing to normal bowel function. This finding will help in the development of new criteria for choice of dietary fiber in the process of developing food products.

Roles of nuclear receptors in the up-regulation of hepatic cholesterol 7alpha-hydroxylase by cholestyramine in rats.

Nuclear receptors are involved in regulating the expression of cholesterol 7alpha-hydroxylase (CYP7A1), however, their roles in the up-regulation of CYP7A1 by cholestyramine (CSR) are still unclear. In the present study, male Wistar rats were divided into four groups and fed [high sucrose + 10% lard diet] (H), [H + 3% CSR diet] (H + CSR), [H + 0.5% cholesterol + 0.25% sodium cholate diet] (C), or [C + 3% CSR diet] (C + CSR) for 2 weeks. Cholestyramine decreased serum and liver cholesterol levels significantly in rats fed C-based diets, but had no effect on these parameters in rats fed H-based diets. Cholestyramine raised hepatic levels of CYP7A1 mRNA and activity in both groups. The gene expression of hepatic ATP-binding cassettes A1 and G5, regulated by liver X receptor (LXR), were unchanged and down-regulated by cholestyramine, respectively. The mRNA levels of the hepatic ATP-binding cassette B11 and short heterodimer partner (SHP), regulated by farnesoid X receptor (FXR), were not changed by cholestyramine. C-based diets, which contained cholesterol and cholic acid, increased SHP mRNA levels compared to H-based diets. Consequently, in rats fed the C+CSR diet, hepatic FXR was activated by dietary bile acids, but the hepatic CYP7A1 mRNA level was increased 16-fold compared to that in rats fed an H diet. These results suggest that cholestyramine up-regulates the expression of CYP7A1 independently via LXR- or FXR-mediated pathways in rats.

Effects of various kinds of edible seaweeds in diets on the development of D-galactosamine-induced hepatopathy in rats.

In the present study we investigated the effects of 11 kinds of edible seaweeds (6 brown and 5 red algae) which contain characteristic seaweed dietary fibers on the induction of D-GalN (D-galactosamine)-hepatopathy in rats (Exps. 1 and 2). Then, the efficacy of various components prepared from Gelidium sp., which was found to alleviate the hepatopathy in Exps. 1 and 2, was examined (Exp. 3). The rats were fed the diets containing various kinds of seaweeds (Exps. 1 and 2), or several components of Gelidium sp. such as total dietary fiber (TDF), soluble dietary fiber (SDF), insoluble dietary fiber (IDF) and dietary fiber-free components (DFFC) (Exp. 3), for 8 d. The rats in all experiments were injected with D-GalN (800 mg/kg body weight) intraperitoneally at the 7th day to induce liver injury and were sacrificed 24 h after the injection of D-GalN. The serum transaminase activities (ALT and AST) and lactate dehydrogenase (LDH) were determined to evaluate the levels of hepatopathy. In Exp. 3, the total GSH concentration in the liver, plasma and cecal contents and organic acid concentration in cecal contents were also evaluated. In Exps. 1 and 2, repressive effects against D-GalN-hepatopathy were shown by four seaweeds Laminaria sp., Gelidium sp., Sargassum fulvellum and Eisenia bicyclis. In Exp. 3, it was found that protective activity in Gelidium sp. against D-GalN-hepatopathy existed not only in the SDF but also in the DFFC fraction. The results in Exp. 3 also indicated that the total GSH but not organic acid concentration in the cecal contents were significantly correlated with serum AST activity, suggesting that the protective effect of Gelidium sp. on D-GalN-hepatopathy in rats is related to GSH metabolism in the intestine.

Effect of dietary fiber in edible seaweeds on the development of D-galactosamine-induced hepatopathy in rats.

Previous studies in our laboratory demonstrated the repressive effect of seaweeds (Laminaria sp., Sargassum fulvellum, Eisenia bicyclis and Gelidium sp.) against D-galactosamine (D-GalN)-induced hepatopathy. However, the mechanism by which these four seaweeds attenuate the D-GalN-hepatopathy has not been completely clarified. This study was carried out to determine the constituents of these seaweeds that protect rats against the D-GalN-hepatopathy. Male Wistar rats were fed for 8 d diets containing 5% seaweeds with or without the antibiotic neomycin (NEO) in experiment 1, and typical seaweed dietary fibers (laminaran, fucoidan, alginate, agar and kappa-carrageenan) of these seaweeds in experiment 2. On the 7th day, the rats were treated with D-GalN (1,900 mg in experiment 1 and 800 mg/kg in experiment 2) and then sacrificed 24 h after the injection of D-GalN. Their serum transaminase (aspartate and alanine aminotransferases: AST and ALT) activities were then determined. In experiment 1, the serum AST and ALT levels in the rats fed the four kinds of seaweeds without NEO were significantly low in comparison to that of the control group, but those with NEO were not significantly different among the groups. In experiment 2, the serum AST and ALT levels in the rats fed fucoidan were significantly low in comparison to those of the other groups fed the dietary fibers and the control. These results suggest that the protective effect of the three kinds of brown seaweeds Laminaria sp., Sargassum fulvellum and Eisenia bicyclis against D-GalN-hepatopathy was caused at least in part by fucoidan.