The objective was to evaluate the effect of replacing milk with soymilk or calcium-fortified soymilk as a part of a meal on postprandial serum phosphorus levels. This study had a randomized crossover design. Ten healthy subjects were enrolled and consumed three test meals that contained either milk, soymilk, or calcium-fortified soymilk containing the same amount of calcium as milk. Blood samples were collected at 0, 30, 60, 120, 240 and 360 min and urine samples were collected from 0 to 360 min after consuming the test meal. Serum phosphorus levels decreased the most after the ingestion of the soymilk meal, and the least after the ingestion of the milk meal. After the ingestion of each meal, serum intact parathyroid hormone levels showed an initial drop followed by a gradual rise, and these changes were more pronounced for the soymilk meal than for the milk meal and the soymilk + calcium meal. Our study shows that replacing milk with soymilk as a part of a meal may suppress the postprandial elevation in serum phosphorus levels, even when the soymilk contains the same amount of calcium as milk.
Elevated levels of cholesterol aldehyde, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A, also called 5,6-secosterol), and its aldolization product (secosterol-B) have been detected in human atherosclerotic plaques and tissues samples of brains affected by neurodegeneration, such as Alzheimer’s disease and Lewy body dementia suggesting that increased formation of these compounds may be associated with inflammation-related diseases. Secosterol-A and secosterol-B, and also further oxidized products seco-A-COOH and seco-B-COOH induce several pro-inflammatory activities in vitro. Accumulating evidences demonstrate that the covalent bindings of these secosterols to target proteins seem to be critical to trigger their pro-inflammatory activities. One of the molecular mechanisms of protein adduct formations is that aldehydic function of secosterol-A and secosterol-B is reactive and form Schiff bases with ɛ- or N-terminal amino groups of proteins. In other cases, it is recently suggested that Michael acceptor moiety formed by the dehydration of not only secosterol-A and secosterol-B but also seco-A-COOH may react with nucleophilic site on target proteins. In this review, I summarize and provide an overview of formation mechanism of secosterols in in vitro and in vivo, patho- or physiological concentrations in biological and clinical samples, and molecular mechanisms of pro-inflammatory activities of secosterols.
In a variety of experimental models, dietary phytochemicals have been demonstrated to exhibit pronounced and versatile bioactivities. Importantly, the possibility of such phytochemicals for human application has been supported in part by epidemiological surveys, which have demonstrated that frequent ingestion of vegetables and fruits containing abundant phytochemicals lowers the risk of onset of various diseases. However, the action mechanisms underlying those dietary phytochemical activities remain to be fully elucidated. For example, even though the anti-oxidant effects of natural polyphenols have long received widespread attention from food scientists, their roles in and contribution to those bioactivities remain controversial because of their poor bioavailability, resulting in extremely low concentrations in the bloodstream. Meanwhile, another important question is why phytochemicals have beneficial effects for animals, including humans, since they are biosynthesized by plants as compounds necessary for adaptation to environmental stress. In regard to that fundamental question, we recently reported novel and unique mechanisms of action of zerumbone, a sesquiterpene with anti-inflammatory and chemopreventive properties. This agent was found to partially exhibit bioactivity through its non-specific interactions with cellular proteins. More strikingly, a non-specific protein binding action of zerumbone was revealed to partially contribute to its anti-inflammatory functions via activation of heat shock factor 1. The present review article highlights and introduces our recent findings regarding the proteo-stress-mediated mechanisms of this phytochemical, along with the concept of hormesis.
Hypercholesterolemia is a major risk factor for cardiovascular diseases. This study investigated the cholesterol-lowering potential of β-caryophyllene in a rat model. Hypercholesterolemia was induced by feeding male Wistar rats a high cholesterol and fat diet for 2 weeks. This was followed by oral administration of β-caryophyllene to hypercholesterolemic rats at 30, 100 and 300 mg/kg b.w. for 4 weeks. A dose of 30 mg/kg of β-caryophyllene significantly lowered serum total cholesterol, low density lipoprotein and the atherogenic index and significantly increased high density lipoprotein level. Moreover, it ameliorated liver injury as evidenced by decreasing hepatomegaly, macrovesicular steatosis and the activity of hepatic marker enzymes alanine aminotransferase and aspartate aminotransferase. Furthermore, it increased the activity of the antioxidant enzyme superoxide dismutase. This dose of β-caryophyllene significantly inhibited the activity of hepatic HMG-CoA reductase. Higher doses (100 and 300 mg/kg) of β-caryophyllene, however, did not induce significant beneficial effects on the studied parameters. These observations demonstrate that β-caryophyllene has a cholesterol-lowering effect on hypercholesterolemic rats, thus offering protection against hypercholesterolemia-induced diseases such as atherosclerosis and fatty liver.
Oxidative stress causes cell death and induces many kinds of disease, including liver disease. Nitroxides are known to react catalytically with free radicals. In this study, the cell protective activities of nitroxides were compared with those of other antioxidants. Nitroxides showed much greater inhibition of hydrogen peroxide-induced cell death than other antioxidants in a hepatic cell line and in primary hepatocytes. The intracellular oxidative stress level at 24 h after hydrogen peroxide stimulation was significantly decreased by nitroxides, but not by other antioxidants. To clarify the mechanism of cell protection by nitroxides, we investigated whether nitroxides inhibited DNA damage and mitogen-activated protein kinase pathway activation. We found that nitroxides reduced caspase-3 activation and may have ultimately inhibited cell death. In conclusion, nitroxides are very useful for attenuating cell damage due to oxidative stress. Nitroxides are thus a potential therapeutic agent for oxidative stress-related diseases.
Nanoparticles are widely used as useful industrial materials. Therefore, their possible adverse health effects must be appraised. We assessed and compared the oxidative DNA damage caused by four different nanoparticles (TiO2, NiO, ZnO and CeO2). The effects of the administration methods, intratracheal instillation and inhalation, were also evaluated. Rats were subjected to intratracheal instillations or 4 weeks of inhalation exposure to the nanoparticles, and the 8-hydroxydeoxyguanosine (8-OHdG) levels in the lung were analyzed by an HPLC-EC detector method. The 8-OHdG levels were increased in a dose-dependent manner with the inhalation of NiO. ZnO also increased the 8-OHdG levels with inhalation. In comparison with the control, the 8-OHdG levels were significantly and persistently higher with the CeO2 nanoparticle administration, by both intratracheal instillation and inhalation. In contrast, there were no significant differences in the 8-OHdG levels between the control and TiO2 nanoparticle-treated groups, with either intratracheal instillation or inhalation during the observation period. These results indicated that NiO, ZnO and CeO2 nanoparticles generate significant amounts of free radicals, and oxidative stress may be responsible for the lung injury caused by these nanoparticles. In addition, both intratracheal instillation and inhalation exposure induced similar tendencies of oxidative DNA damage with these nanoparticles.
This study was conducted to investigate the effect of dietary supplement containing astaxanthin-rich extract derived from Paracoccus carotinifaciens (astaxanthin supplement) on cognitive function of subjects aged 45–64 years. Cognitive functions of 28 subjects orally administered 8 mg astaxanthin/day of astaxanthin supplement for 8 weeks (astaxanthin group) and 26 subjects given a placebo (placebo group) were compared by word memory test, verbal fluency test, and Stroop test. The astaxanthin group experienced significantly larger increase in blood astaxanthin level than the placebo group. However, there were no significant intergroup differences in the results of the tests. A subgroup analysis was performed after dividing subjects into the <55 years old and ≥55 years old age groups. The result of ”words recalled after 5 minutes” in word memory test in <55 years old subjects showed significant improvement in the astaxanthin group than in the placebo group, which was not found in ≥55 years old subjects. Our results indicate that people aged 45–54 years may experience improved cognitive function after ingesting astaxanthin supplement for 8 weeks. On the basis of the parameters tested, administration of astaxanthin supplement was not associated with any problems related to safety.
The gastrointestinal symptoms of irritable bowel syndrome are strongly related to impaired quality of life (QOL), especially in diarrhea-predominant. The gene polymorphisms associated with serotonin, or 5-hydroxytryptamine, alter gastrointestinal symptoms and mental status. We aimed to evaluate the effects of gene polymorphisms on gastrointestinal symptoms, psychological conditions, and QOL, and compare these between patients with diarrhea-predominant irritable bowel syndrome (n = 62) and healthy controls (n = 64). The gene polymorphisms of 5-HTTLPR, 5-HTTVNTR, TPH1 rs453773, and TPH1 rs211105 were evaluated. Gastrointestinal symptoms, depressive state, and QOL were assessed using the Gastrointestinal Symptom Rating Scale, Self-rating Depression Scale, and Short-Form-36. Gene polymorphisms did not significantly differ in frequency between the two groups. The scores for diarrhea, abdominal pain, and indigestion significantly correlated with the physical component summary score. Only the group of patients with diarrhea-predominant irritable bowel syndrome showed a significant correlation between the TPH1 rs211105 T/T genotype and lower scores for role physical and mental health, and higher scores for indigestion and diarrhea. 5-HTTLPR l/s was associated with lower score of role emotional in the diarrhea-predominant irritable bowel syndrome and higher scores in the controls. The gene polymorphisms of 5-hydroxytryptamine signaling effected gastrointestinal symptoms and QOL, especially of the patients with diarrhea-predominant irritable bowel syndrome.
The purpose was to clarify the effects of Helicobacter pylori (H. pylori) eradication on the changes in serum lipid levels by comparing subjects with and without continuous H. pylori infection. The study subjects were 774 individuals (males 536, females 238, mean age 52.6 years) who visited between April 2013 and March 2016 for annual medical checkups. Serum total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and triglyceride levels, and LDLC/HDLC ratio were compared between the subjects with and without H. pylori infection, as well as those with H. pylori eradication subjects. The HDLC level in the H. pylori-positive group was significantly lower as compared to the H. pylori-negative group. The serum level of HDLC in subjects with successful eradication of H. pylori tended to be higher, while the serum levels of total cholesterol, LDLC, and triglycerides tended to be lower in comparison to subjects with continuous H. pylori infection. In addition, the LDLC/HDLC ratio in the H. pylori-positive group was significantly higher than that in the H. pylori-negative group, and successful H. pylori eradication tended to reduce that ratio. In conclusion, successful eradication of H. pylori may have favorable effects on lipid metabolism.
Phosphorus management through dietetic therapy is vital for the prevention of cardiovascular disease in chronic kidney disease patients. There are two main sources of phosphorus in the diet, organic phosphorus from protein and inorganic phosphorus from food additives. The adverse effects of high phosphorus intake on vascular-endothelium function have been reported; however, the differences in the effects of organic phosphorus versus inorganic phosphorus are not clear. In this study, we examined an acute effect of these high phosphorus meals intake on vascular-endothelium function. This was a randomized, double-blind, cross-over test study design targeting healthy young men. We conducted a food intake test using two test meals, one high in organic phosphorus from organic food sources, and one high in inorganic phosphorus from food additives. Endothelium-dependent vasodilation, phosphorus and calcium in the urine and blood, and phosphorus-related hormones were measured preprandial to 120 min postprandial. The results showed higher serum and urine phosphorus values after the high inorganic phosphorus meal, and a significant reduction in endothelium-dependent vasodilation at 30 min postprandial. These findings are evidence that inorganic phosphorus has a stronger influence on vascular-endothelium function than organic phosphorus.
Hyperproduced prostaglandin E2 by cyclooxygenase-2 and microsomal prostaglandin E synthase-1 evokes several pathophysiological responses such as inflammation and carcinogenesis. Our recent study demonstrated that Dioscorea japonica extract suppressed the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 and induced apoptosis in lung carcinoma A549 cells. In the present study, we investigated the effects of Dioscorea japonica on squamous cell carcinoma of mouse skin. Dioscorea japonica feeding and Dioscorea japonica extract topical application suppressed the expression of cyclooxygenase-2, microsomal prostaglandin E synthase-1, interleukin-1β and interleukin-6 and inhibited tumor formation, hyperplasia and inflammatory cell infiltration. Immunohistochemical analyses showed the immunoreactivities of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in tumor keratinocytes and stronger immunoreactivities of cyclooxygenase-2 and hematopoietic prostaglandin D synthase in epidermal dendritic cells (Langerhans cells). Treatment with Dioscorea japonica decreased the immunoreactivity of cyclooxygenase-2 and microsomal prostaglandin E synthase-1. These results indicate that Dioscorea japonica may have inhibitory effects on inflammation and carcinogenesis via suppression of the prostaglandin E2 synthetic pathway.
Low-dose aspirin, which is widely used to reduce the risk of cardio- and cerebrovascular thrombosis, often induces gastroenteropathy by increasing the permeability of the mucosa. However, therapeutic strategies for patients with low-dose aspirin-induced small intestinal injury have not been determined. We evaluated the preventative effect of egualen sodium hydrate, a gastro-protective agent that suppresses indomethacin-induced small-intestinal damage in rats, against small-intestinal mucosal damage induced by low-dose aspirin in healthy adult male volunteers. Participants were randomly allocated to receive aspirin 100 mg/kg daily (control group, n = 10) or aspirin 100 mg/kg plus egualen sodium 1.2 g daily (egualen sodium group, n = 10). Small intestinal mucosal injury was evaluated by capsule endoscopy two weeks after initiation of drug administration. Fecal analyses (occult blood test, immunochemical test, transferrin measurement and calprotectin measurement) were carried out before and after treatment. Egualen sodium significantly suppressed the total number of small intestinal injuries detected by capsule endoscopy and the positive ratio for the fecal occult blood test. Daily use of 1.2 g of egualen sodium showed a preventative effect on low-dose aspirin-induced small intestinal injury. Since acid suppression therapy was reported to exacerbate NSAIDs-induced enteropathy via dysbiosis, egualen sodium may be useful for patients treated with low-dose aspirin.
The exact pathogenesis of diarrhea-dominant irritable bowel syndrome (IBS) is not known, but the abnormal microbiota of the gastrointestinal tract is considered to be one of the important contributing factors as in other gastrointestinal diseases such as inflammatory bowel disease, antibiotic-associated diarrhea, and colorectal cancer as well as systemic diseases. Though diverse trials of probiotics had been continued in the treatment of diarrhea-IBS, only a few proved by randomized clinical trial. To prove the efficacy of Lactobacillus gasseri BNR17 isolated from breast milk in patients with diarrhea-IBS, prospective, randomized, placebo controlled clinical trial was done including health related-quality of life analysis, colon transit time, and the changes of fecal microbiota. BNR17 significantly improved the symptoms of diarrhea compared to control group. Health related-QOL analysis showed significant improvement of abdominal pain, distension, disturbed daily life, and mean defecation frequency with BNR17. On comparative CTT before and after BNR17, 6 out of 24 subjects showed significant correction of rapid colon transit pattern, while only 2 out of 24 in placebo (p<0.01). Upon fecal microbiota analysis, BNR17 significantly increased B. fecalis, E. rectale, C. aerofaciens, F. prausnitzil and B. steroris. Conclusively, Lactobacillus gasseri BNR17 can be a potential probiotics to ameliorate diarrhea-IBS.
The human intestinal microbiota has a close relationship with health control and causes of diseases, and a vast number of scientific papers on this topic have been published recently. Some progress has been made in identifying the causes or species of related microbiota, and successful results of data mining are reviewed here. Humans who are targets of a disease have their own individual characteristics, including various types of noise because of their individual life style and history. The quantitatively dominant bacterial species are not always deeply connected with a target disease. Instead of conventional simple comparisons of the statistical record, here the Gini-coefficient (i.e., evaluation of the uniformity of a group) was applied to minimize the effects of various types of noise in the data. A series of results were reviewed comparatively for normal daily life, disease and technical aspects of data mining. Some representative cases (i.e., heavy smokers, Crohn’s disease, coronary artery disease and prediction accuracy of diagnosis) are discussed in detail. In conclusion, data mining is useful for general diagnostic applications with reasonable cost and reproducibility.
Several environmental factors during the prenatal period transgenerationally affect the health of newborns in later life. Because low-dose antibiotics have been used for promoting the growth of crops and livestock in agriculture, humans may have ingested residual antibiotics for several decades. However, the effect of prenatal administration of low-dose antibiotics on newborns’ health in later life is unclear. In the present study, we found that prenatal treatment of murine mothers with low-dose antibiotics increased the abundance of bacteria of the phylum Firmicutes and the genera Clostridium IV and XIVa in feces from pups. In addition, the body fat percentage of mice in the antibiotic-treated group was higher than those in the control group at 12 weeks of age even though all pups were fed a standard diet. The body fat percentage of all mice was correlated with the abundance of fecal bacteria of Clostridium IV and XIVa. These results predict that low-dose antibiotic administration during the prenatal period affects the gut microbiota of newborns and possibly their health in later life.
We previously reported that type 2 diabetes risk, early impaired glucose tolerance and insulin resistance can be predicted by measuring the fasting levels of certain biomarkers. Here we validated these findings in randomly recruited healthy volunteers (n = 101) based on biomarker expression as well as various non-invasive indices. Weight, body mass index, waist circumference and visceral fat differed between individuals with impaired fasting glucose and/or impaired glucose tolerance, and normal subjects. Fasting plasma levels of glycated hemoglobin, leptin, pro-insulin and retinol binding protein 4 differed between impaired fasting glucose/impaired glucose tolerance and normal subjects group and between newly detected diabetes and normal subjects group. Insulin resistance was correlated with fasting levels of insulin and leptin/adiponectin (r = 0.913); of insulin, retinol binding protein 4 and leptin/adiponectin (r = 0.903); and of insulin, glycated albumin, and leptin/adiponectin (r = 0.913). Type 2 diabetes risk, early impaired glucose tolerance and insulin resistance were predicted with >98% specificity and sensitivity by comparing fasting glucose levels to the estimated Matsuda Index based on fasting levels of insulin, adiponectin and leptin with or without oxidative lineolate metabolites. Non-invasive indices are slightly correlated with glucose tolerance and insulin resistance but do not increase the accuracy of predicting type 2 diabetes risk.
Astaxanthin, a natural antioxidant, exists in non-esterified and esterified forms. Although it is known that astaxanthin can improve exercise endurance and cause metabolic improvement in skeletal muscle, the effects of the two different forms are unclear. We investigated the effects of the different forms of astaxanthin on endurance in mice. Eight-week-old ICR mice were divided into four groups: control; astaxanthin extracted from Haematococcus pluvialis in an esterified form; astaxanthin extracted from Phaffia rhodozyma in a non-esterified form; and astaxanthin synthesized chemically in a non-esterified form. After 5 weeks of treatment, each group was divided into sedentary and exercise groups. In the group fed astaxanthin from Haematococcus, the running time to exhaustion was longest, and the plasma and tissue concentrations of astaxanthin were significantly higher than those in the other groups. Astaxanthin from Haematococcus increased 5'-adenosine monophosphate-activated protein kinase levels in the skeletal muscle. Although the mice in the Haematococcus group ran for longer, hexanoyl lysine adduct levels in the skeletal muscle mitochondria were similar in the control and Haematococcus groups. Our results suggested that esterified astaxanthin promoted energy production and protected tissues from oxidative damage during exercise owing to its favorable absorption properties, leading to a longer running time.
The present study was carried out to investigate the hypoglycemic effect of soy isoflavones from hypocotyl in GK diabetic rats. A single administration and long-term administration tests were conducted in GK diabetic rats to test the hypoglycemic effect of soy isoflavones. At the end of long-term administration trial, blood protein, cholesterol, triglyceride, glycosylated serum protein, C-reactive protein, insulin, aminotransferase, lipid peroxide, interleukin-6, tumor necrosis factor-α were estimated. Inhibition of soy isoflavones against α-amylase and α-glucosidase, as well as on glucose uptake into brush border membrane vesicles or Caco-2 cells were determined in vitro. In single administration experiment, soy isoflavones reduced postprandial blood glucose levels in GK rats. In long-term administration, hypoglycemic effect of soy isoflavones was first observed at week 12 and maintained till week 16. A significant reduction in fasting blood glucose, C-reactive protein, and lipid peroxide was noted at week 16. However, there was no significant treatment effect on blood insulin. Furthermore, soy isoflavone administration resulted in significant decreases in glycosylated serum protein, tumor necrosis factor-α, and interleukin-6. Other biochemical parameters, such as protein, cholesterol, triglyceride and aminotransferases were not modified, however. The results in vitro showed that soy isoflavones showed a potent inhibitory effect on intestinal α-glucosidase, but not on pancreatic α-amylase. Soy isoflavones also decreased glucose transport potency into brush border membrane vesicles or Caco-2 cells. It is concluded that soy isoflavones from hypocotyl, performs hypoglycemic function in GK rats with type 2 diabetes, maybe via suppression of carbohydrate digestion and glucose uptake in small intestine.