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Our aging population and the accompanying decline in immune function is a growing concern that may be addressed by finding natural methods to enhance the immunocompetence of our elderly. Bovine milk and colostrum from cows that have been immunized have been shown to provide additional immunoglobulins and other bioactive molecules that enhance immune function. The purpose of this study was to investigate the ability of hyperimmune bovine colostrum to alleviate the symptoms of rheumatoid arthritis in a murine model. The collagen-induced arthritis DBA/1J murine model was used for this study. Mice were fed colostrum from immunized cows at either 5 or 10 mg/mouse per day or controls for 49 d. The data showed that the colostrum-fed groups had significantly lower total swelling scores and significantly lower collagen-specific antibody (IgG 2a ), inflammation-associated antibody (total IgG), and the inflammatory cytokines tumor necrosis factor α, IL-2, IL-6, and IFN-γ. The results strongly suggest that colostrum from immunized cows may have anti-inflammatory activity in a mouse model of rheumatoid arthritis., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Tangeretin, 4',5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the C max , T max and t 1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC) of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects., (Copyright © 2017. Published by Elsevier B.V.)

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. β-Amyloid (Aβ) has been proposed to play a role in the pathogenesis of AD. Deposits of insoluble Aβ are found in the brains of patients with AD and are one of the pathological hallmarks of the disease, but the underlying signaling pathways are poorly understood. In order to develop antidementia agents with potential therapeutic value, we examined the inhibitory effect of the Nelumbo nucifera seed embryo extracts on to the aggregated amyloid β peptide (agg Aβ 1-40 )-induced damage of differentiated PC-12 cells (dPC-12), a well-known cell model for AD. In the present study, seed embryos of N. nucifera were extracted with 70% methanol in water and then separated into hexane, ethyl acetate, n-butanol, and water layers. Among them, only the n-butanol layer showed strong activity and was therefore subjected to separation on Sephadex LH-20 chromatography. Two fractions showing potent activity were found to significantly inhibit Aβ 1-40 toxicity on dPC-12 cells in increasing order of concentration (10-50 μg/mL). Further purification and characterization of these active fractions identified them to be flavonoids such as rutin, orientin, isoorientin, isoquercetrin, and hyperoside. 2,2-Diphenyl-1-picrylhydrazyl hydrate scavenging activity of the extracts was also carried out to ascertain the possible mechanism of the activity., (Copyright © 2017. Published by Elsevier B.V.)

There have been various effective surgical procedures for the treatment of non-syndromic sagittal craniosynostosis, but no definitive guidelines for management have been established. We conducted a study to elucidate the current state of practice and establish a warranted standard of care. An Internet-based study was sent to 180 pediatric neurosurgeons across the country and 102 craniofacial plastic surgeons in fourteen different countries, to collect data for primary indication for surgical management, preference for timing and choice of surgery, and pre-, peri-, and post-operative management options. The overall response rate from both groups was 32% (n=90/284). Skull deformity was the primary indication for surgical treatment in patients without signs of hydrocephalus for both neurosurgeons and craniofacial surgeons (80% and 63%, respectively). Open surgical management was most commonly performed at six months of age by neurosurgeons (46%) and also by craniofacial surgeons (35%). Open surgical approach was favored for patients younger than four months of age by neurosurgeons (50%), but endoscopic approach was favored by craniofacial surgeons (35%). When performing an open surgical intervention, most neurosurgeons preferred pi or reversed pi procedure (27%), whereas total cranial vault remodeling was the most commonly performed procedure by craniofacial surgeons (37%). The data demonstrated a discrepancy in the treatment options for non-syndromic sagittal craniosynostosis. By conducting/comparing a wide survey to collect consolidative data from both groups of pediatric neurosurgeons and craniofacial plastic surgeons, we can attempt to facilitate the establishment of standard of care., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Metabolic syndrome (MetS), characterized by a constellation of disorders such as hyperglycemia, insulin resistance, and hypertension, is becoming a major global public health problem. Fructose consumption has increased dramatically over the past several decades and with it the incidence of MetS. However, its molecular mechanisms remain to be explored. In this study, we used male Sprague-Dawley (SD) rats to study the pathological mechanism of fructose induced MetS. The SD rats were fed a 60% high-fructose diet for 16 weeks to induce MetS. The induction of MetS was confirmed by blood biochemistry examination. Proteomics were used to investigate the differential hepatic protein expression patterns between the normal group and the MetS group. Proteomic results revealed that fructose-induced MetS induced changes in glucose and fatty acid metabolic pathways. In addition, oxidative stress and endoplasmic reticulum stress-related proteins were modulated by high-fructose feeding. In summary, our results identify many new targets for future investigation. Further characterization of these proteins and their involvement in the link between insulin resistance and metabolic dyslipidemia may bring new insights into MetS., (Copyright © 2016. Published by Elsevier B.V.)

By using the ILSI network in Asia, we are holding a session focused on food safety programs in several Asian areas. In view of the external environment, it is expected to impact the global food system in the near future, including the rapid increase in food demand and in public health services due to population growth, as well as the threats to biosecurity and food safety due to the rapid globalization of the food trade. Facilitating effective information sharing holds promise for the activation of the food industry. At this session, Prof. Hwang shares the current situation of Food Safety and Sanitation Regulations in Taiwan. Dr. Liu provides a talk on the role of risk assessment in food regulatory control focused on aluminum-containing food additives in China. After the JECFA evaluation of aluminum-containing food additives in 2011, each country has carried out risk assessment based on dietary intake surveys. Ms. Chan reports on the activities of a working group on Food Standards Harmonization in ASEAN. She also explains that the ILSI Southeast Asia Region has actively supported the various ASEAN Working Groups in utilizing science to harmonize food standards. Prof. Park provides current research activities in Korea focused on the effect of climate change on food safety. Climate change is generally seen as having a negative impact on food security, particularly in developing countries. We use these four presentations as a springboard to vigorous discussion on issues related to Food Safety in Asia.

Object: Over the past several years, there has been increasing interest in combining angiogenesis inhibitors with radiotherapy and temozolomide chemotherapy in the treatment of glioblastoma. Although the US FDA approved bevacizumab for the treatment of glioblastoma in 2009, the European Medicines Agency rejected its use due to its questionable impact on patient survival. One factor contributing to the failure of angiogenesis inhibitors to increase overall patient survival may be their inability to cross the blood-brain barrier. Here the authors examined in a 9L glioma model whether intracranial polymer-based delivery of the angiogenesis inhibitor minocycline potentiates the effects of both radiotherapy and temozolomide chemotherapy in increasing median survival. The authors also investigated whether the relative timing of minocycline polymer implantation with respect to radiotherapy affects the efficacy of radiotherapy., Methods: Minocycline was incorporated into the biodegradable polymer polyanhydride poly(1,3-bis-[p-carboxyphenoxy propane]-co-[sebacic anhydride]) (CPP:SA) at a ratio of 50:50 by weight. Female Fischer 344 rats were implanted with 9L glioma on Day 0. The minocycline polymer was then implanted on either Day 3 or Day 5 posttumor implantation. Cohorts of rats were exposed to 20 Gy focal radiation on Day 5 or were administered oral temozolomide (50 mg/kg daily) on Days 5-9., Results: Both minocycline polymer implantations on Days 3 and 5 increased survival from 14 days to 19 days (p < 0.001 vs control). Treatment with a combination of both minocycline polymer and radiotherapy on Day 5 resulted in a 139% increase in median survival compared with treatment with radiotherapy alone (p < 0.005). There was not a statistically significant difference in median survival between the group that received minocycline implanted on the same day as radiotherapy and the group that received minocycline polymer 2 days prior to radiotherapy. Lastly, treatment with a combination of minocycline polymer with oral temozolomide resulted in a 38% extension of median survival compared with treatment of oral temozolomide alone (p < 0.001)., Conclusions: These results show that minocycline delivered locally potentiates the effects of both radiotherapy and oral temozolomide in increasing median survival in a rodent glioma model. More generally, these results suggest that traditional therapy in combination with local, as opposed to systemic, delivery of angiogenesis inhibitors may be able to increase median survival for patients with glioblastoma.

Ginseng and lingzhi (Ganoderma lucidum) both are valuable traditional Chinese medicines and have been extensively utilised in functional foods and traditional medicines in many Asian countries. However, massive quantity of ginseng residue is produced after extraction of ginseng which still contains a lot of bioactive compounds such as ginsenosides. The goal of this study was to reuse the American ginseng extraction residue as the fermentation medium of G. lucidum to produce bioactive ginsenoside enriched biotransformation products. The changes of ginsenosides in the fermentation products were analysed during fermentation. Our results showed that after 30 days of fermentation, ginsenoside Rg1, Rd, and compound K (CK) significantly increased, especially Rd, while other ginsenosides (Re, Rb1 and Rc) decreased during fermentation. Ginsenoside Rd is the major ginsenoside in the final fermentation product. Furthermore, the biotransformation of ginsenosides was the major reaction in this fermentation process., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Sinensetin (SIN), one of the major polymethoxyflavones (PMFs) contained mainly in the citrus peels, has been reported to possess various bioactivities, including antifungal, antimutagenic, anticancer, and anti-inflammatory activities. Although the biotransformation of SIN in fungi and insects has been reported, the information about the metabolism of SIN in mammals is still unclear. In this study, formation of SIN metabolites in rats was investigated. Four isotope-labeled SINs ([4'-D3]SIN, [3'-D3]SIN, [5-D3]SIN, and [6-D3]SIN) were synthesized and administered to rat. The urine samples were collected and main metabolites were monitored by ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry. The administered compound and four SIN metabolites were detected in rat urine. These metabolites were identified as 4'-hydroxy-5,6,7,3'-tetramethoxyflavone, 5-hydroxy-6,7,3',4'-tetramethoxyflavone, 6-hydroxy-5,7,3',4'-tetramethoxyflavone, and 7-hydroxy-5,6,3',4'-tetramethoxyflavone sulfate.

In this study, the neuroprotective effect of Dimocarpus longan Lour. flower water extract (LFWE) was investigated. First, an in vitro study showed that LFWE concentration-dependently inhibited lipid peroxidation of brain homogenates incubated at 37 °C. The antioxidative activity of LFWE was more potent than that of glutathione or Trolox. Furthermore, an ex vivo study found that the basal lipid peroxidation (0 °C) and lipid peroxidation incubated at 37 °C were lower in the brain homogenates of LFWE-treated (500 mg/day) rats, indicating that the brain of LFWE-treated rats was more resistant to oxidative stress. Moreover, a Parkinsonian animal model was employed to demonstrate that oral administration of LFWE (125-500 mg/kg/day) dose-dependently attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced neurotoxicity in the nigrostriatal dopaminergic system of rat brain. In conclusion, this study suggests that LFWE is antioxidative, anti-inflammatory, and anti-apoptotic. Furthermore, oral administration of LFWE appears to be useful in preventing and/or treating central nervous system neurodegenerative diseases, including Parkinsonism.

Sesame lignans such as sesamin, sesaminol, and sesamolin are major constituents of sesame oil, and all have a methylenedioxyphenyl group and multiple functions in vivo. It was previously reported that sesaminol, a tetrahydrofurofuran type lignin, was metabolized to mammalian lignans. The present study examined the tissue distribution of sesaminol in Sprague-Dawley (SD) rats. Changes in the concentration of sesaminol and its metabolites (sesaminol glucuronide/sulfate, hydroxymethylsesaminol-tetrahydrofuran, enterolactone, and enterodiol) were determined in tissues within a 24 h period after tube feeding (po 220 mg/kg) to SD rats. The concentrations of enterodiol and enterolactone were significantly higher than those of sesaminol and its tetrahydrofuranoid metabolites in the organs (liver, heart, brain, and kidney). This study demonstrates that sesaminol has potent inhibition of cytochrome P450 (CYPs), compared to tetrahydrofuranoid metabolites. The IC(50) values of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 for sesaminol were determined as 3.57, 3.93, 0.69, 1.33, and 0.86 μM, respectively. In addition, hydroxymethylsesaminol-tetrahydrofuran and enterodiol were weak inhibitors of CYP2C9 and CYP1A2, respectively.

5,7,3',4'-Tetramethoxyflavone (TMF), one of the major polymethoxyflavones (PMFs) isolated from Kaempferia parviflor , has been reported possessing various bioactivities, including antifungal, antimalarial, antimycobacterial, and anti-inflammatory activities. Although several studies on the TMF have been reported, the information about the metabolism of TMF and the structures of TMF metabolites is still not yet clear. In this study, an isotope-labeling method was developed for the identification of TMF metabolites. Three isotope-labeled TMFs (5,7,3',4'-tetramethoxy[3'-D(3)]flavone, 5,7,3',4'-tetramethoxy[4'-D(3)]flavone, and 5,7,3',4'-tetramethoxy[5,4'-D(6)]flavone) were synthesized and administered to rats. The urine samples were collected, and the main metabolites were monitored by ultrahigh-performance liquid chromatography-electrospray ionization-mass spectrometry. Five TMF metabolites were unambiguously identified as 3'-hydroxy-5,7,4'-trimethoxyflavone, 7-hydroxy-5,3',4'-trimethoxyflavone sulfate, 7-hydroxy-5,3',4'-trimethoxyflavone, 4'-hydroxy-5,7,3'-trimethoxyflavone, and 5-hydroxy-7,3',4'-trimethoxyflavone.

Oxidative damage plays an important role in the pathology of human diseases. Ganoderma lucidum, a medicinal fungus, has been used for thousands of years in traditional Oriental medicine. It is reported to have antioxidant functions such as inhibition of lipid peroxidation. The objective of the present study was to investigate the effect of fermentation time on the antioxidative activities of G. lucidum broth filtrate using leguminous plants as part of the liquid fermentation medium. Inhibition of Cu(2+)-induced oxidation of human low-density lipoprotein (LDL), DPPH radical-scavenging activity, total phenolic compounds, isoflavones and protocatechuic acid were measured to evaluate the antioxidant activity of G. lucidum fermentation broth filtrate. Our results showed that black soybean and Astragalus membranaceus improved the antioxidant activity of the G. lucidum fermentation broth filtrate. Protocatechuic acid was identified by LC-MS as the antioxidant compounds whose relative potency of inhibiting LDL oxidation to Trolox is 1.55. Protocatechuic acid showed positive correlation with the antioxidant activity of the fermentation broth filtrate while isoflavones did not contribute to antioxidant activity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Proanthocyanidins constitute an important class of polyphenols ubiquitously found in plants. They have been extensively studied for their antioxidant capacity and bioactivity in vitro and in animal models. However, their stability under different pH conditions and in cell culture medium has not been well documented. In the present study, it was observed that proanthocyanidin A2 (PA2) was relatively more stable in acidic condition than in weak alkaline condition. PA2 was also quite unstable in basal-Dulbecco's Modified Eagle medium (b-DMEM medium) at 37 °C. The addition of PA2 to the cell culture medium accelerated its epimerization with a half-life of <15 min, and ethylenediaminetetraacetic acid (EDTA) could not stop the reaction. The results also demonstrated that the major isomers transformed in the weak alkaline condition or cell culture medium at 37 °C were identified as epicatechin-(4β→8; 2β→O→7)-ent-catechin (proanthocyanidin A4) and epicatechin-(4β→6; 2β→O→7)-ent-catechin. The rates of transformation were dependent on the pH or the components of the medium. Therefore, the results obtained for PA2 in the cell culture bioassays, which were usually carried out for 24 h, might not represent the true activity of the original PA2. The stability and transformation of PA2 should be considered when the bioactivity of PA2 is evaluated in a given cell culture system.

Currently, liver cancer is a leading cause of cancer-related death in the world. Hepatocellular carcinoma is the most common type of liver cancer. Previously, it was reported that blazeispirol A (BA) is the most active antihepatoma compound in an ethanolic extract of Agaricus blazei fermentation product. The aim of this study was to understand the antihepatoma mechanism of BA in human liver cancer Hep 3B cells. The results showed that BA inhibited the growth of Hep 3B cells and increased the percentage of cells in sub-G1 phase in a concentration- and time-dependent manner. In addition, BA treatment resulted in DNA fragmentation, caspase-9 and caspase-3 activations, poly(ADP-ribose)polymerase (PARP) degradation, down-regulation of Bcl-2 and Bcl-xL expressions, up-regulation of Bax expression, and disruption of the mitochondrial membrane potential (MMP) in Hep 3B cells. Furthermore, z-VAD-fmk, a caspase inhibitor, did not enhance the viability of BA-treated Hep 3B cells, and BA induced the release of HtrA2/Omi and apoptosis-inducing factor (AIF) from mitochondria into the cytosol. These findings suggested that BA with novel chemopreventive and chemotherapeutic potentials causes both caspase-dependent and caspase-independent cell death in Hep 3B cells.

Sesame seeds (Sesamum indicum L.) are unique because of potent and various physiological activities imparted by their bioactive lignans. This investigation studied the intestinal distribution and excretion of sesaminol in Sprague-Dawley (SD) rats. To investigate the distribution of sesaminol (per oral 220 mg/kg), the changes in concentration of sesaminol and its metabolites were determined in the intestines and plasma within the 24 h period after tube feeding of sesaminol to SD rats. Results show that the epimerization of sesaminol appeared to be catalyzed by acid in the simulated gastric fluids. The major sesaminol epimer was characterized as 2-episesaminol using 2D-NMR. These findings indicate that sesame sesaminol and its epimer are poorly absorbed prior to reaching the rectum and that substantial amounts pass from the small to the large intestine, where they are metabolized by the colonic microflora to tetrahydrofuranoid metabolites. Sesaminol in plasma was largely present as phase II conjugates, and the seven metabolites were detected as the 2-episesaminol, sesaminol-6-catechol, methylated sesaminol-catechol, R,R-hydroxymethylsesaminol-tetrahydrofuran, S,R-hydroxymethylsesaminol-tetrahydrofuran, enterolactone, and enterodiol. Excretions of sesaminol in urine and feces within the 24 h period were equivalent to 0.02 and 9.33% of the amount ingested, respectively.

trans-Fatty acids in humans not only may be obtained exogenously from food intake but also could be generated endogenously in tissues. The endogenous generation of trans-fatty acids, especially in the cell membranes induced by radical stress, is an inevitable source for the living species. Thiyl radicals generated from thiols act as the catalyst for the cis-trans isomerization of fatty acids. Arachidonic acid (5c,8c,11c,14c-20:4) with only two of the four double bonds deriving from linoleic acid in the diet can be used to differentiate the exogenous or endogenous formation of double bonds. The aim of this study is to evaluate the effective compounds in preventing thiyl radical-induced trans-arachidonic acid formation during UV irradiation in vitro. The trans-arachidonic acids were found to be 75% after 30 min UV irradiation of all-cis-arachidonic acid. Myricetin, luteolin, and quercetin had the highest thiyl radical scavenging activities, whereas sesamol, gallic acid, and vitamins A, C, and E had the lowest. The structures of flavonoids with higher thiyl radical scavenging activities were a 3',4'-o-dihydroxyl group in the B ring and a 2,3-double bond combined with a 4-keto group in the C ring. These effective compounds found in the present work may be used as lead compounds for the potential inhibitors in the formation of trans-fatty acids in vivo.

Sesaminol triglucoside (STG) is the main sesame (Sesamum indicum L.) lignan. Like many other plant lignans, STG can be converted to the mammalian lignans by intestinal microbiota. The objectives of the present study were to investigate the distribution of STG metabolite in rats, and the effects of STG and its metabolite on in vitro inflammation and estrogenic activities. STG was metabolized via intestinal microflora to a biologically active catechol moiety which would then be absorbed into the body in rats. After oral administration of STG to Sprague-Dawley rats, the concentrations of major STG metabolites in rectum, cecum, colon, and small intestines are higher than those in liver, lung, kidney, and heart. Its concentration in brain is low but detectable. The present study demonstrates that STG may be metabolized to form the catechol metabolites first by intestinal microflora and then incorporated via intestine absorption into the cardiovascular system and transported to other tissues. Results showed that the catechol metabolites were found to be able to penetrate the tail end of intestines (large intestine) and go through urinary excretion. STG metabolites significantly reduced the production of IL-6 and TNF-alpha in RAW264.7 murine macrophages stimulated with lipopolysaccharide. The estrogenic activities of STG metabolites were also established by ligand-dependent transcriptional activation through estrogen receptors. This study clearly shows that STG has anti-inflammatory and estrogenic activities via metabolism of intestinal microflora.

Lignan glycosides are important functional compounds in sesame meal. In the present study, we investigated whether the tissue distribution of nano/submicrosized lignan glycosides from sesame meal (N-LGSM) differs from lignan glycosides from sesame meal (LGSM). LGSM was nano/submicrosized with 0.3 mm zirconia beads as the milling media. The average particle size of the 4% LGSM aqueous suspension reduced rapidly from approximately 2 microm to 200 nm after media milling at an agitation speed of 3600 rpm for 30 min. We examined the tissue distribution of sesaminol triglucoside (ST), the main component in LGSM, in Sprague-Dawley (SD) rats. The concentrations of ST were determined in various tissues and plasma within a 24 h period after oral administration of N-LGSM and LGSM (800 mg/kg of body weight). The results showed that higher concentrations of ST and its metabolites (sesaminol, sesaminol sulfate, and sesaminol glucuronide) were found in N-LGSM compared to those in LGSM in most tissues, especially liver and small intestine. Sesaminol glucuronide was the main metabolite in rats. After 3 h of oral administration, around 70% higher concentration of sesaminol glucuronide was found in N-LGSM compared to that in LGSM. This study clearly showed that LGSM is more bioavailable after nano/submicrosizing.

Plant lignans occur widely in foods, with flaxseed recognized as their richest source. Some plant lignans can be converted by intestinal microbiota to the mammalian lignans, enterodiol and enterolactone, which may have protective effects against hormone-related diseases such as breast cancer. This study determined whether plant lignans in sesame seed, particularly sesaminol triglucoside (STG), could be metabolized to mammalian lignans. STG is a furofuran lignan with methylenedioxyphenyls. The transformation of furofuran lignans to mammalian lignans by intestinal microbiota involves the hydrolysis of glucoside, demethylenation of a methylene group, oxidation of dibenzylbutanediol to dibenzylbutyrolactone, and reductive cleavage of furofuran rings. STG has methylenedioxyphenyl moieties in their structures that may require additional oxidative demethylenation of the methylenedioxyphenyl ring for conversion to mammalian lignans. However, STG is metabolized, via intestinal microbiota, to a catechol moiety. The major STG metabolite was characterized as 4-[((3R,4R)-5-(6-hydroxybenzo[d][1,3]dioxol-5-yl)-4-(hydroxymethyl)tetrahydrofuran-3-yl)methyl]benzene-1,2-diol using NMR and mass spectrometry, and STG could be converted to enterolactone and enterodiol by rat intestinal microflora.

Sesame exhibits many beneficial physiological effects, which are mostly related to its lignan compounds, such as sesaminol glucosides. This investigation studies the distribution and elimination of sesaminol triglucoside from sesame in Sprague Dawley (SD) rats. In order to investigate the distribution of sesaminol triglucoside (p.o. 500 mg/kg) in SD rats, the changes in concentration of sesaminol triglucoside and its metabolites were determined in tissues and plasma within 24 h period after tube-feeding to SD rats. Results showed that sesaminol triglucoside may be deglycosylated to form sesaminol first by intestinal microflora and then incorporated via lymphatic absorption into the cardiovascular system, transported to other tissues. The concentrations of sesaminol triglucoside and its metabolites in rectum, caecum, colon, and small intestines are higher than those in liver, lung, kidney, and heart. Its concentration in brain is low but detectable. Glucuronidation and sulfation was the main metabolic pathway for sesaminol in urine, and fecal elimination was a major route of elimination. From LC/MS/MS analysis of rat organs, sesaminol triglucoside can be converted to mammalian lignans, enterodiol (END), and enterolactone (ENL), by rat intestinal microflora. In the plasma, concentrations of END and ENL were 5.9 +/- 0.2 and 5.5 +/- 0.2 micromol/mL, respectively.

Sesamol, generally regarded as a main antioxidative component in sesame oil, is generated from sesamolin upon roasting of sesame seed or during bleaching process of sesame oil. This investigation studied the bioavailability and excretion of sesamol in Sprague-Dawley rats. After oral administration of sesamol (p.o. 100 mg/kg) to SD rats, the changes in concentration of sesamol were determined in various excreta within 24 h period. Our results showed that sesamol conjugated metabolites were rapidly eliminated from urine and feces in 0-4 h. The majority of intact sesamol glucuronide was excreted in the urine. It is suggested that sesamol conjugated metabolites are primarily eliminated from the plasma via the kidney by active tubular secretion. LC-MS/MS analyses of rat excreta showed that sesamol can be converted to 2-methoxybenzene-1,4-diol and benzene-1,2,4-triol in vivo by rat.

Recent evidence strongly suggests that oxidative stress due to redox imbalance is highly associated with metabolic syndrome. The objective of this study was to evaluate the effect of the supplementation of longan flower water extract (LFWE), which showed powerful antioxidative activity in vitro, on markers of metabolic syndrome in a fructose-fed rat model. Male Sprague-Dawley rats were randomly divided into four groups: group C, fed with standard Purina chow; group F, fed with high-fructose diet (HF) alone; group L, fed with HF plus LFWE 125 mg/kg bw per day by gavage; and group H, fed HF plus LFWE 250 mg/kg bw per day by gavage. The dietary manipulation lasted for 14 weeks. Results of our study showed that rats fed with HF resulted in oxidative stress and affected the antioxidant status including plasma thiobarbituric acid and liver antioxidant enzyme activity. Treatment with LFWE significantly augmented the antioxidant system. HF was able to cause insulin resistance and elevation of the blood pressure. The supplementation of LFWE ameliorated insulin resistance by enhancing the expression of insulin signaling pathway related proteins, including insulin receptor substrate-1 and glucose transporter 4. LFWE supplementation was also found to decrease systolic blood pressure. These findings indicate that longan flower water extract may improve the symptoms of metabolic syndrome in fructose-fed rats.

The antihepatoma activity and related active components in the fermentation products of Agaricus blazei (AB) cultured in the medium containing soybean (S) or black soybean (BS) were investigated. AB(BS)-pE and AB(S)-pE were the ethanolic extracts from the fermentation products of AB(BS) and AB(S), respectively. According to the IC 50 values, AB(BS)-pE (161.1 and 24.0 microg/mL for Hep 3B and Hep G2 cells, respectively) exhibited stronger cytotoxicities against hepatoma cells than AB(S)-pE (>200 and 99.9 microg/mL for Hep 3B and Hep G2 cells, respectively). AB(BS)-pE was separated by silica gel column chromatography and eluted with n-hexane/ethyl acetate/methanol gradient solvent system into 21 fractions. Fraction 3 [AB(BS)-pE-F3], eluted with n-hexane/ethyl acetate (97:3 and 19:1, v/v), was the most active fraction having inhibitory activity on the proliferation of Hep 3B and Hep G2 cells (IC 50 of 3.6 and 1.9 microg/mL, respectively). Three major compounds, compounds 1- 3, were further isolated from the AB(BS)-pE-F3 fraction by reversed-phase semipreparative high-performance liquid chromatography. Compounds 2 and 3 gave better antihepatoma activity than that of compound 1. The IC 50 values of compounds 2 and 3 were 2.8 and 4.5 microg/mL for Hep 3B cells and 1.4 and 2.0 microg/mL for Hep G2 cells, respectively. The structures of compounds 2 and 3 were identified by UV, IR, electron impact mass spectrometry, and (1)H and (13)C NMR to be blazeispirols A and C, respectively. Blazeispirols A and C existed in the mycelia but not in the broth and were more in AB(BS)-pE (49.9 +/- 8.9 and 14.2 +/- 2.4 mg/g, respectively) than AB(S)-pE (15.9 +/- 1.7 and 3.9 +/- 0.6 mg/g, respectively). Additionally, the result shows that the production of blazeispirols A and C was increased after cultivation in the medium containing black soybean on day 6 and reached the maximum on day 12, and the contents of blazeispirols A and C were negatively correlated with Hep 3B and Hep G2 cell viabilities ( r = -0.84 to -0.93, P < 0.01). It suggests that blazeispirols A and C could be used as biomarkers to produce the fermentation product of A. blazei with antihepatoma activity.

Sesamol, generally regarded as the main antioxidative component in sesame oil, can be generated from sesamolin by roasting sesame seed or bleaching sesame oil. This paper reports the bioavailability of sesamol in Sprague-Dawley (SD) rats. Biological fluid was sampled following a dose of sesamol of 50 mg/kg by gastric gavage (p.o.) or by intravenous injection. The pharmacokinetic data of sesamol were calculated by noncompartmental model. The tissue distribution of sesamol (p.o., 100 mg/kg) in SD rats was also investigated. The concentration changes of sesamol were determined in various tissues and plasma within a 24 h period after oral administration of sesamol. The results showed that the oral bioavailability of sesamol was 35.5 +/- 8.5%. Sesamol was found to be able to penetrate the blood-brain barrier and go through hepatobiliary excretion. Sesamol conjugated metabolites were widely distributed in SD rat tissues, with the highest concentrations in the liver and kidneys and the lowest in the brain. It is postulated that sesamol is incorporated into the liver first and then transported to the other tissues (lung, kidneys, and brain). The major metabolites of sesamol distributed in the lung and kidney were glucuronide and sulfate.

Three different solvent extracts (methanol, ethyl acetate, and n-hexane) of longan ( Dimocarpus longan Lour.) flowers were assayed with three different antioxidant capacity methods, namely, the DPPH free radical scavenging effect, the oxygen radical absorbance capacity (ORAC) assay, and the inhibition of Cu(2+)-induced oxidation of human low-density lipoprotein (LDL). It was revealed that the methanol extract has the best antioxidative activity, followed by ethyl acetate and n-hexane extracts. The methanol extract was separated by liquid-liquid partition into n-hexane, ethyl acetate, n-butanol, and water fractions. The ethyl acetate fraction was found to have the highest activity of delaying LDL oxidation. After silica gel column chromatography, the fraction having a superior activity was identified as containing two major compounds, (-)-epicatechin and proanthocyanidin A2.

Anthocyanidins found in certain flowers have been shown to act as strong antioxidants in various systems, exhibiting multiple biological actions. The antioxidative effects of water extract and ethanolic extract of longan (Dimocarpus longan Lour.) flowers were evaluated by radical scavenging activity and compared to those of gallic acid, myricetin, and epigallocatechin gallate. In this study, the suppressive effects of longan flower extracts on nitric oxide and prostaglandin E2 production were investigated using a lipopolysaccharide-stimulated RAW 264.7 cell model. Abundant levels of phenolic compounds including flavonoids, condensed tannins, and proanthocyanidins were found in water or ethanolic extracts prepared from dried longan flowers. The antioxidative effect of longan flower extract was similar to the effect exhibited by pure antioxidants. Moreover, longan flower extract showed prominent inhibitory effects on prostaglandin E2 production. Significant concentration-dependent inhibition of nitric oxide production was detected when cells were cotreated with lipopolysaccharide and various concentrations of longan flower extracts. These inhibitory effects were further attributed to suppression of inducible nitric oxide synthase protein expression and not to reduced enzymatic activity. These results suggest that longan flower crude extracts, especially ethanolic extract, have antioxidant and anti-inflammatory effects, and the probable mechanism involves inhibition of inflammation by proanthocyanidins. Preliminary observations suggest that longan flower extract, especially alcoholic extract, could be another potential source of natural dietary antioxidant and anti-inflammatory agent.

Bag teas, packed 3g of ground black, green, oolong, paochoung and pu-erh tea leaves (the particle size used was 1-2mm), were steeped in 150 mL of 70, 85 or 100 degrees C hot water to study the effects of the number of steeping (the same bag tea was steeped repeatedly eight times, 30s each time, as done in China for making ceremonial tea) and varied steeping durations (0.5-4 min) on caffeine, catechins and gallic acid in tea infusions. The changes in tea infusions during storage at 4 or 25 degrees C for 0-48 h and the variations in these compounds of bag tea infused with 150 mL of 4 or 25 degrees C cold water for 0.5-16 h were also investigated. A HPLC method with a C18 column and a step gradient solvent system consisting of acetonitrile and 0.9% acetic acid in deionized water was used for analysis. Results for all kinds of tea samples showed that the second tea infusion contained the highest contents of caffeine, catechins and gallic acid when bag teas were steeped in 70 degrees C water. It was different from that steeped at 85 and 100 degrees C, the highest contents existed in the first infusion. These compounds decreased gradually in later infusions. Higher amounts of caffeine, catechins and gallic acid could be released from bag teas as hotter water was used. As steeping duration prolonged, these ingredients increased progressively, however, their levels were lower than that cumulated from the infusions with the identical bag tea prepared recurrently at the same temperature and time points. (-)-Gallocatechin gallate and (+)-catechin existed in these tea infusions rarely and could not be detected until a certain amount of them infusing. Except gallic acid that showed a significant increase and caffeine that exhibited no significant change, all kinds of catechins decreased appreciably after tea infusions were stored at 25 degrees C for 36 h; nevertheless, all of them showed no evident changes at 4 degrees C storage. The caffeine, catechins and gallic acid in tea infused with cold water also increased with increasing duration. Their contents in 25 degrees C steeped tea were higher than that made at 4 degrees C; moreover, their infusion rates from bag teas to cold water were markedly lower than that steeped in hot water. Infusing efficiencies of non-gallated catechins were higher than gallated catechins under cold water steeping.

Conversions of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, from lactone forms to their corresponding hydroxy acid form in 0.1 N NaOH or 0.05 N KOH (prepared with 25, 50, 75, 90% acetonitrile or methanol in water or 100% water) were evaluated. Results showed that lactone form statins could be transformed almost completely only in alkaline solutions prepared with 25 or 50% acetonitrile. In all methanolic alkaline solutions, lactone form statins could also be converted entirely, nevertheless, they would be further transformed to the methyl ester of the hydroxy acid form and the transformation increased as methanol rises. When lactone and hydroxy acid forms of statins were in methanol, ethyl acetate, 70% acetonitrile in water (with 0.5% acetic acid or no) for 0-48 h at room temperature or in 100 degrees C water for 0-2 h, lactone form statins were converted to their corresponding hydroxy acids, which were raised as time extends and the highest conversions of them were about 35% in 100 degrees C water and 70% acetonitrile, slightly transformed for lactone form statins in 70% acetonitrile (with 0.5% acetic acid) after 8 h, and the other treatments for all statins showed no significant changes. Interferences would be reduced efficiently when statins were extracted from Pu-Erh tea with methanol, ethyl acetate or 100 degrees C water followed by purifying through a C18 solid-phase extraction cartridge. Lovastatin was the only statin found in Pu-Erh tea and the highest content of it was found under ethyl acetate extraction. In ethyl acetate and methanol extracts, lovastatin existed merely as lactone form. The lowest content of lovastatin was found in the 100 degrees C water extract of Pu-Erh tea, however, both of lactone and hydroxy acid forms were found to exist in the extract.

Background: Sprague-Dawley rats fed a fructose-rich diet exhibit insulin resistance and hypertension, a pathologic status resembling human type II diabetes mellitus, and are an excellent laboratory animal model for research on insulin action and the development of hypertension. Since green tea has numerous beneficial effects, we tested its effect on fructose-fed rats., Aim: The present study was therefore designed to further evaluate the effects of green tea supplementation on insulin resistance, hypertension, and the glucose transporters I and IV contents in adipose tissue in the fructose-fed rat model., Methods: The animals were divided into three groups and fed for 12 weeks with standard chow and water (control group), a high fructose diet and water (fructose group), or the same high fructose diet, but with green tea (0.5 g of lyophilized green tea powder dissolved in 100 mL of deionized distilled water) instead of water (fructose/green tea group). During the 12 weeks study period, fresh water or green tea was provided daily at 6:00 PM. Blood pressure was measured twice a week, and an oral glucose tolerance test performed after 12 weeks of diet supplementation. At the end of the experiment, plasma triglyceride (TG), free fatty acid (FFA), glucose, and insulin were assayed. The epididymal fat pads from all rats in the same group were pooled and adipocytes isolated and tested for insulin binding, glucose uptake, and their content of glucose transporters I (GLUT I) and IV (GLUT IV)., Result: Compared to the control group, the fructose group developed fasting hyperglycemia, hyperinsulinemia, and elevated blood pressure. Insulin-stimulated glucose uptake and insulin binding of adipocytes were significantly reduced, and the glucose transporter IV content of adipocytes also decreased. The fructose/green tea group showed improvement in all of these metabolic defects and in insulin resistance and blood pressure., Conclusion: Based on these results, we suggest that the amelioration of insulin resistance by green tea is associated with the increased expression of GLUT IV.

A compilation of literature data on the content of cholesterol oxidation products (COP) in various food products and in blood demonstrates a large variation in content in products or tissues of very similar nature when analyzed in different laboratories according to a large number of methods. The lack of validated, internationally recognized methodology with published accuracy and precision has so far hindered such assessments. Hence an interlaboratory comparision of methodologies of COP analysis was undertaken on egg yolk powders (EYP), whole milk powders (WMP), skim milk powders (SMP), and lard (L). Each product type had one fresh sample (low) and one aged (high) in COP contents. A total of 17 sets of results on WMP, 15 on SMP and EYP, and 13 on L were compared. Overall results (mg/kg sample) varied extensively: Fresh EYP 0.72-265, aged EYP 2.51-361; fresh WMP 0.02-18.1, aged WMP 0.02-26.9; fresh SMP 0.02-6.51, aged SMP <0.01-6.51; fresh L 0.18-97, aged L 4.15-452. Some results were questioned, viz., those from laboratories not indicating substantial differences between samples "low" and "high" in total COP. Others were excluded because of lack of verification of identity of gas chromatographic peaks by mass spectrometry. Then a more narrow range of core results (mg/kg sample) was observed: Fresh EYP 5.69-29.5 sample, aged EYP 11.8-79.0; fresh WMP 0.12-1.76, aged WMP 1.17-13.7; fresh SMP <0.30-<1.21, aged SMP 0.30-2.26; fresh L 0.18-5.07, aged L 94.4-231. At a workshop discussing the results, numerous recommendations were made toward more reliable methodology for determination of COP in foods.

Epidemiological observations and laboratory studies have shown that green tea has a variety of health effects, including antitumor, antioxidative, and hypolipidemic activities. The aim of this study was to examine whether it had an effect on glucose tolerance and insulin sensitivity in Sprague-Dawley rats. In experiment 1 (in vivo study), rats were divided into two groups: a control group fed standard chow and deionized distilled water and a "green tea" group fed the same chow diet but with green tea instead of water (0.5 g of lyophilized green tea powder dissolved in 100 mL of deionized distilled water). After 12 weeks of green tea supplementation, the green tea group had lower fasting plasma levels of glucose, insulin, triglyceride, and free fatty acid than the control rats. Insulin-stimulated glucose uptake of, and insulin binding to, adipocytes were significantly increased in the green tea group. In experiment 2 (in vitro study), a tea polyphenol extract was used to determine its effect on insulin activity in vitro. Green tea polyphenols (0.075%) significantly increased basal and insulin-stimulated glucose uptake of adipocytes. Results demonstrated that green tea increases insulin sensitivity in Sprague-Dawley rats and that green tea polyphenol is one of the active components.

A new furostanol pentaoligoside and spirostanol tetraoligoside were isolated for the first time from yam tubers (Dioscorea pseudojaponica Yamamoto) from Taiwan, together with four known yam saponins, methyl protodioscin, methyl protogracillin, dioscin, and gracillin. Their structures were characterized as 26-O-beta-D-glucopyranosyl-22alpha-methoxyl-(25R)-furost-5-en-3beta,26-diol, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-([alpha-L-rhamnopyranosyl-(1-->4)]-O-[alpha-L-rhamnopyranosyl-(1-->4)])-beta-D-glucopyranoside, and (25R)-spirost-5-en-3beta-ol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-O-([alpha-L-rhamnopyranosyl-(1-->4)]-O-[alpha-L-rhamnopyranosyl-(1-->4)])-beta-D-glucopyranoside. The structural identification was performed using LC-MS and 1H and 13C NMR. The methanol extract of yam tubers was fractionated by XAD-2 column chromatography using a methanol/water gradient elution system to yield furostanol and spirostanol glycoside fractions. Preparative high-performance liquid chromatography, employing a C18 column and a mobile phase of methanol/water (69:31, v/v), was used to separate each furostanol glycoside, whereas a mobile phase of methanol/water (79:21, v/v) was used to resolve the individual spirostanol glycosides. The conversions from steroid saponins to diosgenin after acid hydrolysis were around 68 and 90% for furostanol and spirostanol glycosides, respectively.

The antioxidative property of green tea against iron-induced oxidative stress was investigated in the rat brain both in vivo and in vivo. Incubation of brain homogenates at 37 degrees C for 4 hours in vitro increased the formation of Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Auto-oxidation (without exogenous iron) of brain homogenates was inhibited by green tea extract in a concentration-dependent manner. Moreover, incubation with iron (1 microM) elevated lipid peroxidation of brain homogenates after 4-hour incubation at 37 degrees C. Co-incubation with green tea extract dose-dependently inhibited the iron-induced elevation in lipid peroxidation. For the in vivo studies: ferrous citrate (iron, 4.2 nmoles) was infused intranigrally and induced degeneration of the nigrostriatal dopaminergic system of rat brain. An increase in lipid peroxidation in substantia nigra as well as a decrease in dopamine content in striatum was observed seven days after the iron infusion. Intranigral infusion of green tea extract alone did not increase, and in some cases, even decreased lipid peroxidation in substantia nigra. Co-infusion of green tea extract prevented oxidative injury induced by iron. Both iron-induced elevation in lipid peroxidation in substantia nigra and iron-induced decrease in dopamine content in striatum were suppressed. Oral administration of green tea extract for two weeks did not prevent the iron-induced oxidative injury in nigrostriatal dopaminergic system. Our results suggest that intranigral infusion of green tea extract appears to be nontoxic to the nigrostriatal dopaminergic system. Furthermore, the potent antioxidative action of green tea extract protects the nigrostriatal dopaminergic system from the iron-induced oxidative injury.

Health damage and environmental pollution are serious problems caused by betel quid chewing in Taiwan. Many people acquire the habit of chewing betel quid due to its physiological effects, including increased stamina and a general feeling of well-being. In this study, a sympathetic model system of adrenal chromaffin cells and sensory evaluation were used to examine the physiological effects of betel quid and the interaction of all the ingredients (areca fruit, Piper betle inflorescence and red time paste) in betel quid. Physiological effects of cardioacceleration, a slightly drunk feeling, sweating and salivation occurred during the chewing of betel quid (a mixture of areca fruit, Piper betle inflorescence and red lime paste) and a mixture of areca fruit and red lime paste. Both induced much more basal catecholamine secretion from adrenal chromaffin cells than did other ingredients and combinations of ingredients. It was evident that the responses in the sympathetic model system were closely correlated with the physiological feeling of well-being. The inhibitory effects of all the chewing juices on catecholamine secretion evoked by carbachol and a high concentration of potassium (high K+) showed that they perhaps affected the calcium influx through voltage-sensitive channels or the steps involved in secretion after calcium entry to stimulate basal catecholamine secretion from chromaffin cells.

Squid oil was microencapsulated by spray drying method. Gelatin, sodium caseinate, maltodextrin were contained in spray drying formulation with or without lecithin and microcrystalline cellulose (Avicel). The thermal stability of the unencapsulated and encapsulated squid oils was determined by pressure differential scanning calorimetry (PDSC), Fourier transform infrared (FT-IR) microscopic photometer with DSC system and themogravimetric analysis (TGA). The results indicate that the above analytical apparatus is an easy and reliable method to investigate the samples and that the microcapsule prepared by spray-dried formulation with lecithin as an emulsifier and Avicel as a stabilizer exhibits more stable thermal stability and longer shelf-life.

Crocin dyes, isolated from Gardenia jasminodes, did not affect hepatic function when they were orally administered to rats in a daily dose of 50 mg/kg for 8 days, but could induce acute hepatic discoloration. A high dosage of 100 mg/kg for 2 weeks could induce both hepatic damage and black pigmentation, but a lower dose of 100 mg/kg for 40 days did not. Rats fed on diet containing 1% of crocin dyes for four months were shown to have mild hepatic functional disorders and pigmentation. The black pigmentation of the liver and the acute hepatic damage associated with the discoloration were completely reversible. During the period of hepatic pigmentation caused by high dose of crocin dyes, the urine had abnormally increased porphyrin excretion and tended to display a blackish green color. The skin also appeared purplish black. The mechanism of black pigmentation seemed to correlate with the gradual accumulation of crocin dyes. In summary, the crocin dyes have a very low toxicity in rats even in high experimental dosage which would hardly happen in human practice. It is therefore suggested that the crocin dyes are safe for coloring foods.

Formation of the Moloney murine leukemia virus envelope mRNA involves the removal of a 5,185-base pair-long intron. Deletion analysis of two Moloney murine leukemia virus-derived expression vectors revealed the existence of two short regions within the viral intron which are required for the efficient formation of the spliced RNA species. One region was present upstream from the 3' splice junction, extended at least 85 nucleotides beyond the splice site, and was not more than 165 nucleotides long. As yeast polymerase II introns, the Moloney murine leukemia virus intron contains the sequence 5'-TACTAAC-3' 15 nucleotides upstream from the 3' splice site. A second region located in the middle of the intron, within a 560-nucleotide-long sequence, was also essential for formation of the spliced RNA species. The efficient splicing of the env mRNA in the absence of expression of viral genes raises the possibility that similar mechanisms are used to remove introns of (some) cellular genes.