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High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p

Background and aims: Sarcopenia is recognized as a major public health issue, because it is prevalent in the elderly, especially those who live in long-term care facilities. The purpose of this study was to investigate the beneficial effects of milk or soy milk combined with resistance exercise on the muscle mass and muscle strength of individual elderly nursing home residents with sarcopenia. Methods: This study was a randomized controlled trial (clincaltrials.gov as NCT05035121) that recruited very old (&gt, 75 years) subjects with sarcopenia in a nursing home (Su-Ao and Yuanshan Branches, Taipei Veterans General Hospital) from June to December 2017. Thirty-five elderly (84.9 ± 6.1 years old) subjects were recruited and divided into three groups: control (n = 12), milk supplemented (n = 12), and soy milk supplemented (n = 11). All participants joined a mild resistance exercise training program three times a week (30 min/time). Moreover, elderly subjects in the milk and soy milk groups drank 200 mL of milk or soy milk for breakfast and as a snack after exercise. Results: After 12 weeks, compared to the baseline, calf circumferences had significantly increased in the control and soy milk groups (p = 0.0362 and p = 0.0197, respectively). Hand grip strength had significantly improved in the milk and soy milk groups (p = 0.0407 and p = 0.0096, respectively). In addition, there was no difference among the three groups. Conclusions: Mild resistance exercise combined with milk or soy milk improved the calf circumference and hand grip strength in very old nursing home residents with sarcopenia.

An imbalance of energy intake and expenditure leads to fat accumulation and metabolic disorders. The aim of the study was to investigate the effects of antroquinonol on diet-induced obesity. Thirty-two rats were divided into a control group (C), an obesogenic group (OB), and two experimental groups consuming 25 (OB-AQ25) and 50 mg/kg (OB-AQ50) antroquinonol (n = 8). After a 12-week experimental period, we collected blood, liver, abdominal fat, and gastrocnemius muscle tissue for analysis. The obesogenic diet induced greater weight gain and fat accumulation, and increased hepatic lipids, and tumor necrosis factor-α and interleukin-1β concentrations in rats. Antroquinonol consumption reduced epididymal and hepatic lipids and inflammatory cytokines. We found that antroquinonol upregulated hepatic adenosine monophosphate-activated protein kinase and downregulated sterol regulatory element-binding protein-1 protein expressions and downregulated fatty acid synthase mRNA expression. In addition, gastrocnemius fibronectin type III domain containing 5 protein expression was also higher in the B group. In conclusion, our results suggested that consuming antroquinonol may ameliorate diet-induced abdominal and hepatic fat accumulation. PRACTICAL APPLICATION: Antroquinonol is a bioactive compound derived from Antrodia camphorate which is traditionally used in Chinese medicinal cuisine, and is used for developing functional foods in Taiwan. This is the first study investigating the possible effects of antroquinonol on obesity and we found that antroquinonol can ameliorate diet-induced obesity, and therefore may be used in further studies and functional food development.

The objective of this study was to evaluate the effects of the hot-water extract of defatted Camellia oleifera seeds (CSE) on body and liver fat accumulation in rats. Forty rats were divided into 5 groups and each group was fed either an isocaloric control diet or a high-fat liquid diet with 0% (H), 0.12% (H1), 0.24% (H2), or 0.48% CSE (H3) for 8 weeks. Ingestion of the high-fat liquid diet increased abdominal and liver fat accumulation, although no difference was found in body weights compared with rats fed the control diet. We found that rats fed the H2 and H3 diets had lower plasma alanine aminotransferase activities than the H group in the fourth and eighth weeks. At the end of the study, the H2 and H3 groups also had lower epididymal and retroperitoneal fat masses, and all CSE groups had lower circulatory leptin levels than the H group. CSE consumption decreased hepatic fat accumulation in terms of liver triglycerides and a histopathology analysis, and ameliorated high-fat diet-induced elevation of hepatic tumor necrosis factor-α levels. We also found that CSE groups had lower malondialdehyde and hydroxyproline levels in the liver. Our results suggested that CSE may exert beneficial effects through decreasing body fat accumulation and hepatic steatosis and regulating adipokine levels in diet-induced nonalcoholic fatty liver disease.

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.

The purpose of this study was to investigate whether or not Coriandrum sativum seed extract (CSSE) can ameliorate memory impairment in senescence-accelerated mouse-prone 8 (SAMP8) mice. Sixteen 10-week-old male SAMP8 mice were divided into two groups, which were orally administrated water (SAMP8(&minus, )) or CSSE (200 mg/kg/day, SAMP8(+)). Eight 10-week-old male Institute of Cancer Research (ICR) mice were used as a normal control group and were also orally administrated water. The mean escape time in the Barnes maze test of SAMP8(&minus, ) mice was significantly longer than that of ICR mice. However, SAMP8(+) mice showed a shorter mean escape time compared to that of SAMP8(&minus, ) mice. Neurofilament messenger (m)RNA levels significantly decreased in the frontal lobe of SAMP8(&minus, ) mice when compared with ICR mice, but significantly increased in SAMP8(+) mice relative to SAMP8(&minus, ) mice. In addition, mRNA levels of inducible nitric oxide synthase (iNOS) and neuronal (n)NOS significantly increased in the frontal lobe of SAMP8(&minus, ) mice, but only the mRNA level of nNOS significantly decreased in SAMP8(+) mice. These results indicated that continuous oral administration of CSSE for 12 weeks could ameliorate aging-induced memory declines in the senescence-accelerated SAMP8 mouse model.

Clinical and animal experiments indicated that gut-derived endotoxin and imbalanced intestinal microbiota contribute to the pathogenesis of alcoholic liver disease (ALD). In this study, we investigated whether synbiotic supplementation could improve ALD in rats by altering the intestinal microbial composition and improving the intestinal integrity. Male Wistar rats were divided into four groups according to plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and subjected to either a normal liquid diet (C), a normal liquid diet with synbiotic supplementation (C + S), an ethanol liquid diet (E), or an ethanol liquid diet with synbiotic supplementation (E + S) for 12 weeks. Results revealed that the ethanol-fed group showed increases in plasma AST and ALT activities, the endotoxin level, the hepatic triglyceride (TG) level, and hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels, and a decrease in the hepatic IL-10 level. Ethanol-feeding also contributed to increased intestinal permeability and decreased fecal bifidobacteria and lactobacilli amounts. However, synbiotic supplementation effectively attenuated the plasma endotoxin, hepatic TG and TNF-α levels, and increased the hepatic IL-10 level. Furthermore, synbiotic supplementation protected the rats against ethanol-induced hyperpermeability of the intestine, and significantly increased amounts of bifidobacteria and lactobacilli in the feces. This study demonstrated that synbiotics possess a novel hepatoprotective function by improving the intestinal permeability and microbiota in rats with ethanol-induced liver injury.

Dysregulated iron metabolism is associated with altered body composition and nonalcoholic fatty liver disease (NAFLD); however, mechanisms underlying this association remain undefined. We investigated this association in 117 women. Middle-aged women (≥45 years old (y)) were heavier and had lower serum iron, higher serum hepcidin, ferritin, and severe NAFLD incidence than young adult women (

The properties of confined liquid water, or liquid water in contact with hydrophobic surfaces, are significantly different from those of bulk liquid water. However, all of water's commonly described properties are related to inert "bulk liquid water" which comprises a tetrahedral hydrogen-bonded network. In this work, we report an innovative and facile method for preparing small water clusters (SWCs) with reduced affinity hydrogen bonds by letting bulk water flow through supported Au nanoparticles (NPs) under resonant illumination to give NP-treated (AuNT) water at constant temperature. Utilizing localized surface plasmon resonance on illuminated Au NPs, the strong hydrogen bonds of bulk water can be disordered when water is located at the illuminated Au/water interface. The prepared SWCs are free of Au NPs. The energy efficiency for creating SWCs is ∼17%. The resulting stable AuNT water exhibits distinct properties at room temperature, which are significantly different from the properties of untreated bulk water, examples being their ability to scavenge free hydroxyl and 2,2-diphenyl-1-picrylhydrazyl radicals and to effectively reduce NO release from lipopolysaccharide-induced inflammatory cells.

The objective of the present study was to investigate the effects of β-conglycinin and soya isoflavones on diabetic nephropathy (DN). DN was induced by an intravenous injection of streptozotocin (25 mg/kg) in spontaneously hypertensive rats. DN rats were divided into a non-diabetic group (C, control group) and three DN groups (D, DN with control diet; B, DN+control diet with one-eighth of casein replaced by β-conglycinin as the protein source; and I, DN+control diet with 0·01 % soya isoflavones). After a 4-week experimental period, we found that fasting blood sugar and plasma and kidney advanced glycation end product levels and 24 h urinary protein excretion of the B group were significantly lower than those of the D group and insulin sensitivity and nephrin expression of the B group were significantly higher than those of the D group. In addition, systolic blood pressure, angiotensin-converting enzyme activity, angiotensin II level and plasma TAG level of the B group were significantly lower than those of the D group, whereas only the levels of plasma TAG and thiobarbituric acid-reactive substances of the I group were lower than those of the D group. In conclusion, β-conglycinin may be beneficial for retarding DN progression and this effect cannot be completely explained by its isoflavone content.

The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys. Results showed that administration of methylglyoxal-bovine serum albumin (MG-BSA) AGE accelerated renal MG, carboxyethyl lysine, carboxymethyl lysine and malondialdehyde formation and, in parallel, the levels of serum creatinine and blood urea nitrogen (BUN) were significantly increased. Expression of RAGE and NLRP3 inflammasome-related proteins (TXNIP, NLRP3, procaspase-1 and caspase-1) and IL (interleukin)-1β secretion were upregulated, whereas the levels of EPCs, eNOS and NO were lower in MG-BSA-treated mice. This induction by MG-BSA was significantly inhibited by RAGE antagonist. Our results firstly reveal a possible mechanism of AGE-mediated renal dysfunction upon NLRP3 inflammasome activation. Therapeutic blockade of RAGE may ameliorate renal and endothelial functions in subjects under high AGE burden.

Objective This investigation attempted to clarify the effects of soy protein on alcoholic liver disease (ALD) in rats undergoing ethanol withdrawal. Methods Alcoholic liver disease was induced in rats by administration of a low-carbohydrate ethanol liquid diet for 12 weeks, after which the ethanol was withdrawn and the rats were divided into two experimental groups: a control group (EC group) and a soy protein group (EP group) for 4 weeks. Results After the 12-week ALD-inducing period, the ethanol group had significantly higher hepatic lipid accumulation, oxidative stress and inflammation. We found that the EP group had significantly lower hepatic lipids, malondialdehyde, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, hydroxyproline levels and myeloperoxidase activity compared to the EC group. Moreover, the fecal total cholesterol and total lipids were higher in the EP group. Expression of the hepatic cytochrome P450 2E1 (CYP2E1) protein in the EP group was significantly lower than that in the EC group, and the hepatic peroxisome proliferator-activated receptor (PPAR) α and cytochrome P450 4A (CYP4A) protein expressions in the EP group were significantly higher than those in the EC group. In the histopathological analysis, we also found that soy protein ameliorated fat accumulation in the liver. Conclusion These results suggest that soy protein may improve alcohol-induced lipid accumulation, oxidative stress and inflammation by decreasing proinflammatory cytokines and CYP2E1 protein expression and by increasing PPARα and CYP4A protein expressions and fecal lipid excretion, thereby producing beneficial effects on ALD during ethanol withdrawal.

The purpose of this study was to investigate the effects of glutamine supplementation on inflammatory responses in chronic ethanol-fed rats. Male Wistar rats weighing about 160 g were divided into five groups. Two groups were fed a normal liquid diet and three groups were fed a glutamine-containing liquid diet. After 1 week, one of the normal liquid diet groups was fed an ethanol-containing liquid diet (CE), and the other group served as the control (CC) group. At the same time, one of the glutamine-containing liquid diet groups was continually fed the same diet (GCG), but the other two groups were fed ethanol-containing diet supplemented with glutamine (GEG) or without glutamine (GE). The following items were analyzed: (1) liver function, (2) cytokine contents, and (3) hepatic oxidative stress. The activities of aspartate transaminase (AST) and alanine transaminase (ALT) and levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the CE group had significantly increased. In addition, hepatic cytochrome P450 2E1 (CYP2E1) expression had significantly increased in the CE, GE and GEG groups. However, the activities of AST and ALT and levels of TNF-α and IL-1β in the GE group were significantly lower than those of the CE group. The results suggest that the plasma inflammatory responses of rats fed an ethanol-containing liquid diet for 7 weeks significantly increased. However, pretreatment with glutamine improved the plasma inflammatory responses induced by ethanol.

Endothelial dysfunction leads to elevation of blood pressure and vascular remodeling, which may result in tissue injuries. The aim of this study was to investigate the mechanisms and effects of antroquinonol on hypertension and related renal injuries. Rats were fed water containing 25 mg/kg/day N&omega, nitro-l-arginine methyl ester (L-NAME) to induce hypertension, and a diet with or without antroquinonol (20 or 40 mg/kg/day) for a 9-week experiment. During the experimental period, antroquinonol reduced the elevation of systolic and diastolic blood pressure. At the end of the study, we found that the antroquinonol groups had lower serum creatinine, renal endothelin-1, angiotensin II, and malondialdehyde levels and arteriole thickening. We found that the 40 mg/kg/day antroquinonol group had lower renal nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activities, greater nuclear factor erythroid-2, and heme oxygenase-1 expressions. Moreover, we also found that antroquinonol decreased proinflammatory cytokine concentrations in the kidney by modulating the nuclear factor-&kappa, B pathway. These results suggest that antroquinonol may ameliorate hypertension and improve renal function by reducing oxidative stress and inflammation in rats with endothelial dysfunction.

The study was designed to evaluate the effects of 1 μM β-carotene on antioxidant status in ethanol-treated rat hepatocytes and investigate possible anti-apoptotic mechanisms of β-carotene in protecting ethanol-induced cytotoxicity. The isolated rat hepatocytes were incubated for 48 h in a medium with or without alcohol (100 mM) and μ-carotene (1 μM) using the following groups: the control (C), β-carotene (CB), ethanol (E), and ethanol + β-carotene (EB) groups. The cell viability, antioxidative status, cytochrome P450 2E1 (CYP2E1) and caspase expressions in hepatocytes were measured. The E group demonstrated lower cell viability, glutathione (GSH) levels, and lipid peroxide accumulation in rat hepatocytes; meanwhile, CYP2E1, caspase-3, and caspase-9 expressions increased. In contrast, cell viability, GSH levels, and glutathione reductase (GRD) activity significantly increased while lipid peroxides and expressions of CYP2E1, casapse-3, and caspase-9 decreased in the EB group. The results suggest that ethanol treatment decreases cell viability in rat hepatocytes via induced oxidative stress. 1 μM β-carotene decreased oxidative stress and prevented ethanol-induced cell death by inhibiting caspase-9 and caspase-3 expression. Copyright © 2009 John Wiley & Sons, Ltd.

To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl(4))-induced hepatic oxidative stress in male Sprague-Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl(4) group (CCl(4) injection), silymarin group (CCl(4) injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl(4) injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl(4) injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl(4) group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl(4) group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl(4) group by 25%. These results suggest that the schisandrin B-sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl(4)-induced hepatic oxidative stress.

We investigated the effects of soy protein and soy protein hydrolysate on blood pressure control, angiotensin-converting enzyme (ACE) activity, and renal function in a rat chronic renal failure model. Rats that had undergone a 5/6 nephrectomy were separated into three groups and fed different experimental diets for 14 weeks. At the end of the study, rats that fed a diet containing soy protein as the protein source had better blood pressure control and renal function, as well as lower circulating ACE activity and renal tumor-necrosis factor-alpha (TNF-alpha) concentration than rats fed a casein protein diet. Soy protein hydrolysate was shown to be as effective as soy protein in preventing the elevation of blood pressure, the progression of renal failure, and decreases in kidney TNF-alpha level, plasma ACE activity, and insulin concentration. In conclusion, the beneficial effects of consuming soy protein on blood pressure and renal function may be mediated mostly by its pepsin-digested hydrolysate through its ACE inhibitory activity.

This study investigated the effects of soymilk on lipid metabolism in Sprague-Dawley rats fed a cholesterol-enriched (0.3%) diet.Thirty male Sprague-Dawley rats weighing 230.0 +/- 9.8 g were randomly assigned to one of three groups: control, S1 (containing 15% soymilk powder in the diet), and S2 (22.5%). After 8 wk, lipid profiles of the plasma, liver, and feces were determined.Body weight gain, daily food intake, and feeding efficiency showed no differences across groups (P0.05). The experimental groups had significantly lower plasma levels of cholesterol, triacylglycerol, and low-density lipoprotein cholesterol than the control group (P0.05) at weeks 4 and 8. However, total fecal excretion of neutral steroid did not significantly differ across groups (P0.05).Soymilk affects the metabolism of plasma cholesterol in Sprague-Dawley rats.

We examined the angiotensin I-converting enzyme (ACE) inhibitory activity and antihypertensive effect of the hot water extract of wakame, Undaria pinnatifida. Ten dipeptides were isolated from the extract by several steps of chromatography, and their amino acid sequences were Tyr-His, Lys-Trp, Lys-Tyr, Lys-Phe, Phe-Tyr, Val-Trp, Val-Phe, Ile-Tyr, Ile-Trp, and Val-Tyr. Both single administration and repeated oral administration of synthetic Tyr-His, Lys-Tyr, Phe-Tyr, and Ile-Tyr significantly decreased blood pressure in spontaneously hypertensive rats.

The aim of this study was to investigate the inhibitory activity of angiotensin-convening enzyme (ACE) and antihypertensive effects of soybean protein hydrolysate in spontaneously hypertensive rats (SHRs). The inhibitory activities against ACE with an IC 50 of the peptidic fraction were 0.82 (casein), 0.73 (soybean protein isolate), and 0.48 mg/mL (soybean acid-precipitated protein), respectively. Peptic hydrolysate containing 1 % NaCl was added to the SHRs' feed (5% of each protein hydrolysate). Systolic blood pressure of the soybean protein hydrolysate-supplemented groups were significantly lower than that of the casein hydrolysate-supplemented group in the study period. These data suggested that soybean protein hydrolysate may retard the development of hypertension in SHRs by its ACE inhibitory effect in vivo.

This study investigated the effect of supplementation with chicken extract on plasma and colostrum protein compositions in lactating women. Thirty healthy pregnant women were evenly divided into the control (n = 15) or chicken extract (CE) group (n = 15). The CE group was given one bottle (70 mL/bottle) of chicken extract three times a day to provide 18 g protein from the 37th week pregnancy to 3 days postpartum. All women in the CE group consumed chicken extract at least for 2 weeks (18 +/- 5 days). High protein supplement was restricted in the control group. Blood samples were collected during the 37th week pregnancy and 3-day postpartum, and milk was collected during 3-day postpartum. The results showed that plasma total protein was significantly lower by 14% in the CE group compared with that in the control group during 3-day postpartum. Plasma epidermal growth factor (EGF) significantly elevated by 236% during 3-day postpartum compared with those during the 37th week pregnancy in the CE group. The levels of lactoferrin, EGF, and transforming growth factor-beta2 (TGF-beta2) in colostrum significantly increased by 34%, 62%, and 196%, respectively, in the CE group compared with those in the control group. However, the levels of total protein, casein, lactalbumin, and secretory immunoglobulin A in colostrum did not significantly differ between two groups. Therefore, supplementation with chicken extract increased colostrum levels of lactoferrin, EGF, and TGF-beta2, which are important for the growth and immune functions of the infants, in lactating women.

The objective of the present experiment was to examine the effect of substituting different quantities of soyabean protein for casein on renal function and lipid metabolism in rats with chronic renal failure induced by a five-sixths nephrectomy. Experimental animals were subjected to a nephrectomy and fed either casein or soyabean protein (200 or 100 g/kg diet). The diets were isoenergetic with identical fat, Na, K and P contents. Rats ingesting 200 g casein/kg diet showed a significantly (PP

Peptides having potent antioxidant activity were separated from the hydrolysate of wheat gluten by ion-exchange and gel filtration chromatography. Peptides obtained by SP Sephadex C-25 chromatography of the most active fraction (WP-3) were further separated using reversed-phase high performance liquid chromatography. The amino acid sequences of these peptides were Leu-Gln-Pro-Gly-Gln-Gly-Gln-Gln-Gly and Ala-Gln-Ile-Pro-Gln-Gln.

Peptidic fractions which inhibit angiotensin I-converting enzyme (ACE) were separated from peptic digests of soybean by ion exchange chromatography and gel filtration. Further separation of the peptidic fractions by ODS HPLC afforded active peptides, the amino acid sequences of which were identified by Edman 's procedure as: Ile-Ala (inhibitory against ACE with an IC 50 of 153 μM), Tyr-Leu-Ala-Gly-Asn-GIn (14 μM), Phe-Phe-Leu (37 μM), Ile-Tyr-Leu-Leu (42 μM), and Val-Met-Asp-Lys-Pro-Gln-Gly (39 μM). The antihypertensive activity of the soybean peptides was also investigated. Peptide fractions (2.0 g/kg body weight, oral administration) markedly lowered the blood pressure of spontaneously hypertensive rats (SHRs).

This study was performed to investigate the effects of the peptic undigested fraction derived from soybean protein hydrolysate (UDSP) on lipid metabolism in rats fed a cholesterol-enriched diet (1%). Eighteen male Wistar rats weighing 205-235 g were randomly divided into three groups: the control group (20% casein), U2 (18% casein + 2% UDSP), and U5 group (15% casein + 5% UDSP). After 4 weeks, rats were sacrificed, and the lipid profiles of the plasma, liver, and feces were determined. Body weight gain, daily food intake, and liver weight showed no differences among the groups, but the feeding efficiency ratio in the U5 group was significantly lower than that in the other groups (P < 0.05). There were no changes in plasma cholesterol, LDL-C, HDL-C, and liver cholesterol levels in each group. However, the U5 group showed a significantly lower VLDL-C compared to the control and U2 groups. In addition, the plasma and liver TG content were lower in the U2 and U5 groups than in the control group (P < 0. 05). Moreover, the fecal bile acid and total neutral steroid excretions were higher in the U2 and U5 groups (P < 0.05) compared to the control group.

Peptides having potent antioxidant activity were separated from the hydrolysate of wheat gluten by ion-exchange and gel filtration chromatography. Peptides obtained by SP Sephadex C-25 chromatography of the most active fraction (WP-3) were further separated using reversed-phase high performance liquid chromatography. The amino acid sequences of these peptides were Leu-Gln-Pro-Gly-Gln-Gly-Gln-Gln-Gly and Ala-Gln-Ile-Pro-Gln-Gln.

The peptidic fractions that inhibited angiotensin I-converting enzyme (ACE) were separated from the peptic digests of 2 microalgae, Chlorella vulgaris and Spirulina platensis, by ion exchange chromatography and gel filtration. Oral administration of peptidic fractions into spontaneously hypertensive rats at 200 mg/kg of body weight resulted in marked antihypertensive effects. Further separation of the peptidic fractions by ODS high-performance liquid chromatography furnished the following active peptides: Ile-Val-Val-Glu (inhibitory against ACE with an IC(50) of 315.3 microM), Ala-Phe-Leu (63.8 microM), Phe-Ala-Leu (26.3 microM), Ala-Glu-Leu (57.1 microM), and Val-Val-Pro-Pro-Ala (79.5 microM) from C. vulgaris; Ile-Ala-Glu (34.7 microM), Phe-Ala-Leu, Ala-Glu-Leu, Ile-Ala-Pro-Gly (11.4 microM), and Val-Ala-Phe (35.8 microM) from S. platensis.

Immunostimulative peptides were isolated from the pepsin digest of soybean by ion exchange, gel filtration, and reversed-phase high-performance chromatography. The peptides formed blastoids against the splenocytes of CSH/HeN mice. The amino acid sequences of these peptides were: Ala-Glu-lle-Asn-Met-Pro-Asp-Tyr, Ile-Gln-Gln-Gly-Asn, and Ser-Gly-Phe-Ala-Pro, respectively.

Chronic hepatitis/cirrhosis is the eighth leading cause of death in Taiwan. Excess accumulated extracellular matrix produced by activated hepatic stellate cells (HSCs) is the major cause of liver fibrosis. Ginsenoside Rb1, the most active compound purified from ginseng, has been considered to be hepatoprotective. This study investigated the effects of ginsenoside Rb1 (98.8% purity) on activation, proliferation, and profibrotic factors in rat HSC-T6 cells under H₂O₂ oxidative stress. Rat HSC-T6 cells were activated by 10 nM H₂O₂ and then incubated with different concentrations of ginsenoside Rb1 (5, 10, 20, 40, and 80 μg/mL) for 24 hours. Medium containing 0.08% dimethyl sulfoxide or 5 mM N-acetyl-l-cysteine was used as a negative or positive control, respectively. The results showed that ginsenoside Rb1 at 5-40 μg/mL significantly reduced α-smooth muscle actin levels and at 5-80 μg/mL inhibited cell proliferation in HSC-T6 cells after induction with H₂O₂ (P.05). Collagen secreted by HSC-T6 cells was decreased by ginsenoside Rb1 at 5-80 μg/mL (P.05). Protein expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-1 was suppressed by ginsenoside Rb1 at 10-80 μg/mL (P.05). In addition, mRNA expression of type I and III collagen, TGF-β1, and TIMP-1 was inhibited by ginsenoside Rb1 (10 and 80 μg/mL) (P.05). Therefore, ginsenoside Rb1 exerted an antifibrotic effect on HSCs by inhibiting activation, proliferation, and expression of collagen, TGF-β1, MMP-2, and TIMP-1.

Objective The purpose of this study was to investigate the protective effects of combined treatment of folate and vitamin B12 against alcoholic liver disease. Methods Male Wistar rats weighing about 160 g were divided into four groups: an ethanol group fed an ethanol liquid diet; a control group pair-fed an isoenergetic diet without ethanol; an ethanol and vitamin group fed an ethanol-containing diet that was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day); and a control and vitamin group fed an isoenergetic diet without ethanol, which was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day). Results After 16 wk, the plasma folate concentration in the ethanol group was significantly lower than in the other three groups. The plasma homocysteine concentration in the ethanol group was significantly higher than in the other three groups. The hepatic matrix metalloproteinase-2 concentration in the ethanol group was significantly higher than in the control and ethanol/vitamin groups. Furthermore, the plasma homocysteine concentration at the 16th week and the hepatic matrix metalloproteinase-2 concentration showed a significant positive correlation in rats of each group. In addition, pathologic evidence of liver fibrosis was observed only in the ethanol group. Furthermore, hepatic cytochrome 2E1 protein expression in group E increased significantly. Conclusion These results suggest that combined treatment of folate and vitamin B12 can alleviate alcoholic liver injury that may be related to normalization of plasma homocysteine levels.

The study was designed to evaluate the effects of 1 microM beta-carotene on antioxidant status in ethanol-treated rat hepatocytes and investigate possible anti-apoptotic mechanisms of beta-carotene in protecting ethanol-induced cytotoxicity. The isolated rat hepatocytes were incubated for 48 h in a medium with or without alcohol (100 mM) and mu-carotene (1 microM) using the following groups: the control (C), beta-carotene (CB), ethanol (E), and ethanol + beta-carotene (EB) groups. The cell viability, antioxidative status, cytochrome P450 2E1 (CYP2E1) and caspase expressions in hepatocytes were measured. The E group demonstrated lower cell viability, glutathione (GSH) levels, and lipid peroxide accumulation in rat hepatocytes; meanwhile, CYP2E1, caspase-3, and caspase-9 expressions increased. In contrast, cell viability, GSH levels, and glutathione reductase (GRD) activity significantly increased while lipid peroxides and expressions of CYP2E1, casapse-3, and caspase-9 decreased in the EB group. The results suggest that ethanol treatment decreases cell viability in rat hepatocytes via induced oxidative stress. 1 muM beta-carotene decreased oxidative stress and prevented ethanol-induced cell death by inhibiting caspase-9 and caspase-3 expression.

Objective Non-alcoholic steatohepatitis (NASH) is a common cause of liver disease, and it may progress to fibrosis or cirrhosis. The aim of this study was to investigate the effects of soy protein on hepatic steatosis and insulin resistance in NASH. Methods Forty male Sprague-Dawley rats were fed a high-fat diet for 4 wk to induce NASH and then were allocated to one of four diets: a NASH-inducing diet, a standard diet, a NASH-inducing diet plus soy protein, and a standard diet plus soy protein. Results After the 10-wk experimental period, the results showed that soy protein significantly lowered plasma cholesterol concentrations and body fat accumulation. Soy protein intake also decreased the hepatic lipid depots of triacylglycerols and cholesterol and decreased the concentrations of lipid peroxides. In an analysis of antioxidative status, rats fed the soy protein diet showed improved antioxidative potential due to increases in superoxide dismutase and catalase activities and a decrease in the protein expression of cytochrome P450 2E1. Conclusion Soy protein may improve the liver function in patients with NASH by lowering lipid levels in the blood and liver, increasing the antioxidative capacity, and improving insulin resistance.

This study examined the effects of beta-carotene on antioxidant status in rats with chronic alcohol consumption. At the beginning of experiment (week 0), according to both the plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, rats (n = 24) were divided into 3 groups and fed with a standard diet (group C), a diet containing ethanol (group E), or a diet containing ethanol and beta-carotene (group E+B). After 10 weeks, plasma AST and ALT, fat accumulation in the liver, antioxidant enzyme activities in erythrocytes and the liver, malondialdehyde (MDA), and alpha-tocopherol and retinol in plasma and hepatic samples were analyzed. The chronic alcohol diet significantly increased AST and ALT levels in plasma, and these changes were prevented by supplementing the diet with beta-carotene. Glutathione (GSH) in erythrocytes and in the liver was significantly elevated in rats fed with a diet containing beta-carotene. The results indicate that beta-carotene supplementation can prevent ethanol-induced liver damage and increase GSH concentrations in erythrocytes and the liver.

In traditional Chinese medicine (TCM), purgation is indicated when a person suffers an illness due to the accumulation of evil internal heat. Obese individuals with a large belly, red face, thick and yellow tongue fur, constipation, and avoidance of heat are thought accumulates of evil internal heat, and they are also treated with purgatives such asTa-Cheng-Chi-Tang(TCCT),Xiao-Chen-Chi-Tang(XCCT), andTiao-Wei-Chen-Chi-Tang(TWCCT) by TCM doctors. In previous studies, our group found that TCCT has potent anti-inflammatory activity, and that XCCT is an effective antioxidant. Since rhubarb is the principle herb in these three prescriptions, we will first present a thorough review of the literature on the demonstrated effect (or lack of effect) of rhubarb and rhubarb-containing polyherbal preparations on lipid and weight control. We will then continue our research with an investigation of the anti-obesity and lipid-lowering effect of TCCT, XCCT, TWCCT, and rhubarb extracts using two animal models. TWCCT lowered the serum triglyceride concentration as much as fenofibrate in Triton WR-1339-treated mice. Daily supplementation with XCCT and TWCCT significantly attenuated the high-fat-diet-induced hypercholesterolemia in rats. In addition, TWCCT also significantly lowered the high-fat-diet-induced hypertriglycemia. Although feeding high-fat diet rats with these extracts did not cause loose stools or diarrhea or other deleterious effects on renal or hepatic function. None of these extracts lowered the body weight of rats fed on high-fat diet. In conclusion, the results suggest that XCCT and TWCCT might exert beneficial effects in the treatment of hyperlipidemia.

To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl(4))-induced hepatic oxidative stress in male Sprague-Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl(4) group (CCl(4) injection), silymarin group (CCl(4) injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl(4) injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl(4) injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl(4) group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl(4) group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl(4) group by 25%. These results suggest that the schisandrin B-sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl(4)-induced hepatic oxidative stress.

Pepsin-digested soy protein hydrolysate (SPH) has been reported to be responsible for many of the physiological benefits associated with soy protein consumption. In the present study, we investigated the effects of SPH with angiotensin-converting enzyme (ACE) inhibitory potential on blood pressure and renal injuries in rats with N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension. Rats were fed a diet containing L-NAME (50 mg/kg body weight) with or without SPH (at 1%, 3%, or 5%) for 6 weeks. We found that ingestion of SPH ameliorated the development of hypertension during the 6-week experimental period. SPH was also found to ameliorate renal function by decreasing urinary protein excretion and elevating the creatinine clearance rate. The levels of kidney ACE activity, malonaldehyde, tumor necrosis factor-a and plasminogen activator inhibitor-1, and the expression of CYP4A decreased in the 5% SPH group. Consumption of 5% SPH also ameliorated renal damage according to the histopathological analysis. These findings suggest that SPH might ameliorate the elevation of blood pressure and show renoprotective effects in nitric oxide (NO)-deficient rats, and one possible mechanism might be mediation via its ACE inhibitory activity.

This investigation attempted to clarify the hypolipidemic effects of non-dialyzed soybean protein hydrolysate (NSPH), which is hydrolyzed by pepsin from soybean acid-precipitated protein (APP), in rats fed a cholesterol-rich diet.Forty Sprague-Dawley rats were divided into four groups as the control group (19.7% casein), the APP group (14.7% casein + 5% APP), the NSPH group (14.7% casein + 5% NSPH), and the ISO group (19.7% casein + 0.0013% soy isoflavone).After 12-week experimental period, the APP and NSPH groups had a significant lower plasma total cholesterol, triglycerides, and LDL-cholesterol concentrations compared with the control group. Additionally, the atherosclerosis index in APP and NSPH group had also markedly decreased. Liver cholesterol and triglyceride contents of the APP and NSPH group were significantly lower than those of the control group. There were no different in plasma LDL-C, liver cholesterol and triglycerides between the ISO group and control group. Fecal excretion of neutral steroids and nitrogen compounds was significantly higher in the APP and NSPH groups than that in the control group. An in vitro study also showed that NSPH, compared with casein, obviously decreased cholesterol micellar solubility.These results suggested that NSPH may decrease lipid accumulation in the liver and have a hypolipidemic effect by enhancing excretion and inhibiting absorption of lipids.

Pepsin-digested soy protein hydrolysate has been reported to be responsible for many of the physiological benefits associated with soy protein consumption. In the present study, we investigated the effects of soy protein hydrolysate with angiotensin-converting enzyme (ACE) inhibitory potential on the blood pressure and cardiovascular remodeling in rats with N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension. Rats were fed a diet containing L-NAME (50 mg/kg body weight) with or without soy protein hydrolysate (1%, 3% or 5%) for 6 weeks. We found that ingestion of soy protein hydrolysate retarded the development of hypertension during the 6-week experimental period without affecting the amount of food intake. Although there was no difference in plasma ACE activity or tissue nitric oxide levels, ACE activity in the heart of rats consuming soy protein hydrolysate was significantly lower than that of the control group. Moreover, cardiac malonaldehyde and tumor necrosis factor-alpha concentrations were also lower in the soy protein hydrolysate group. No difference in plasminogen activator inhibitor-1 level was found in plasma or cardiovascular tissue. In the histopathological analysis, we also found that soy protein hydrolysate ameliorated inflammation and left ventricle hypertrophy in the heart. These findings suggest that soy protein hydrolysate might not only improve the balance between circulating nitric oxide and renin-angiotensin system but also show beneficial effects on cardiovascular tissue through its ACE inhibitory activity.

Studies have demonstrated that isolated soya protein (ISP) can slow the progression of renal injury, reduce blood pressure and improve the serum lipid profile in experimental animals and human subjects. The mechanisms and components of soya responsible have not been fully established. The present study was designed to evaluate the effects of the hydrophilic supernatant fraction (SF) and the hydrophobic precipitate fraction (PF) isolated from soya protein hydrolysate on renal function, lipid metabolism and blood pressure in five-sixths nephrectomized rats. Experimental animals were subjected to a nephrectomy and allocated to four groups (180 g casein/kg, 180 g ISP/kg, 100 g casein/kg with 80 g SF/kg, and 100 g casein/kg with 80 g PF/kg). The SF group had the most significant decreases in blood pressure and total cholesterol, as well as a significantly retarded progression of the experimentally induced renal disease, compared with the other groups. The PF group exhibited a significantly increased faecal excretion of total steroids. The serum creatinine, level of proteinuria, total cholesterol and LDL-cholesterol concentrations, and blood pressure were significantly reduced, and HDL-cholesterol was significantly increased, in the ISP and PF groups compared with the casein group, but no significant differences were observed between the ISP and PF groups. These results suggest that both soya protein hydrolysate fractions favourably affected chronic renal failure induced by a five-sixths nephrectomy, and the hydrophilic fraction of soya protein hydrolysate had the most pronounced effect on attenuating hypertension and slowing the progression of renal disease.

Clinical trials have shown that soya protein reduces the concentrations of some atherogenic lipids in subjects with normal renal function. The present study examined the effects of soya protein on serum lipid concentrations and lipoprotein metabolism in patients on hypercholesterolaemic haemodialysis. Twenty-six hypercholesterolaemic (total cholesterol ≥6·21mmol/l) patients on haemodialysis were studied in a randomized, double-blind, placebo-controlled clinical trial. After a 4-week run-in phase, the subjects were randomly assigned to two groups. Isolated soya protein or milk protein 30g was consumed daily as a beverage at breakfast or post-dialysis for 12 weeks. Soya protein substitution resulted in significant reductions in total cholesterol (17·2 (sd8·9)%), LDL-cholesterol (15·3 (sd12·5)), apo B (14·6 (sd12·1)%) and insulin (23·8 (sd18·7)%) concentrations. There were no significant changes in HDL-cholesterol or apo A-I. These results indicate that replacing part of the daily protein intake with soya protein has a beneficial effect on atherogenic lipids and favourably affects lipoprotein metabolism in hypercholesterolaemic patients undergoing haemodialysis.