Sesamin attenuates intercellular cell adhesion molecule‐1 expression in vitro in TNF‐α‐treated human aortic endothelial cells and in vivo in apolipoprotein‐E‐deficient mice

Sesame lignans have antioxidative and anti‐inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial‐leukocyte adhesion molecules in tumor necrosis factor‐α (TNF‐α)‐treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 μM), the TNF‐α‐induced expression of intercellular cell adhesion molecule‐1 (ICAM‐1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM‐1 expression (30% decrease at 100 μM). Sesamin and sesamol reduced the marked TNF‐α‐induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM‐1 mRNA. Both significantly reduced the binding of monocytes to TNF‐α‐stimulated HAECs. Sesamin significantly attenuated TNF‐α‐induced ICAM‐1 expression and cell adhesion by downregulation of extracellular signal‐regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM‐1 expression seen in aortas of apolipoprotein‐E‐deficient mice. Taken together, these data suggest that sesamin inhibits TNF‐α‐induced extracellular signal‐regulated kinase/p38 phosphorylation, nuclear translocation of NF‐κB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM‐1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.     

Riboflavin at High Doses Enhances Lung Cancer Cell Proliferation,Invasion, and Migration

The influence of riboflavin (vitamin B₂) upon growth, invasion, and migration in non‐small cell lung cancer cell lines was evaluated. Riboflavin at 1, 10, 25, 50, 100, 200, or 400 μmol/L was added into A549, H3255, or Calu‐6 cells. The effects of this compound upon level and/or expression of reactive oxygen species (ROS), inflammatory cytokines, intercellular adhesion molecule (ICAM)‐1, fibronectin, matrix metalloproteinase (MMP)‐9, MMP‐2, focal adhesion kinase (FAK), nuclear factor kappa B (NF‐κB), and mitogen‐activated protein kinase (MAPK) were examined. Results showed that riboflavin at test doses did not affect the level of ROS and glutathione. Riboflavin at 200 and 400 μmol/L significantly enhanced cell growth in test lung cancer cell lines, and at 400 μmol/L significantly increased the release of interleukin‐6, tumor necrosis factor‐alpha, and vascular endothelial growth factor. This agent at 200 and 400 μmol/L also upregulated protein production of ICAM‐1, fibronectin, MMP‐9, MMP‐2, NF‐κB p50, p‐p38 MAPK, and FAK; and at 400 μmol/L enhanced invasion and migration in test cell lines. These findings suggested that riboflavin at high doses might promote lung cancer progression.     

Edible Filamentous Fungi from the Species Monascus: Early Traditional Fermentations,Modern Molecular Biology,and Future Genomics

Monascus spp. are filamentous fungi famous for their fermented products, especially red mold rice (RMR), a traditional fermented food in East Asian areas with a very long edible history documented back to the Han dynasty (BC 202‐AD 220) in China. Nowadays, RMR and its related products involve a very large industry from artisanal traditional fermentations to food companies to medicine manufacturers, which are distributed worldwide. Modern studies have shown that Monascus spp. are able to produce abundant beneficial secondary metabolites, such as monacolins (cholesterol‐lowering agents), γ‐amino butyric acid (an antihypertensive substance), dimerumic acid (an antioxidant), and pigments (food‐grade colorants), and some strains can also secrete citrinin, a nephrotoxic metabolite. Monascus‐related studies have received much attention because of their wide applications. However, to our knowledge, no systematic review on the progress of Monascus research has ever been published. In this review, the progress of research on Monascus is summarized into 3 stages: Monascus fermentation, Monascus molecular biology, and Monascus genomics. This review covers the past history, current status, and future direction of Monascus research, contributing to a comprehensive understanding of Monascus research progress.     

Production and antioxidant activity of alcoholic beverages made from various cereal grains using Monascus purpureus NBRC 5965

Monascus sp., which produces red pigments, has been utilized for brewing red alcoholic beverages and fermented foods in China and Okinawa, Japan. Novel red alcoholic beverages with antioxidant activity were made from cereal grains of various colours utilizing the saccharifying activity of Monascus purpureus NBRC 5965. The alcoholic beverage made from black rice and beni koji prepared with M. purpureus NBRC 5965 showed a deep red colour, and the DPPH radical scavenging activity of the alcoholic beverage made from black rice and beni koji was around a 3300 µm Trolox equivalent/mL‐beverage. The antioxidant activity of this alcoholic beverage is thought to be a result of the combination of Monascus pigments and black rice anthocyanin. The DPPH radical scavenging activity and inhibitory activity of lipid peroxidation of an alcoholic beverage made with beni koji were higher than those of an alcoholic beverage made with ki koji prepared with Aspergillus oryzae. Copyright © 2016 The Institute of Brewing & Distilling     

Immunomodulatory activities and antioxidant properties of polysaccharides from Monascus-fermented products in vitro

BACKGROUND: Monascus ‐fermented products have featured in Chinese cuisine for thousands of years and are widely used as food colourants and dietary materials in many Asian countries. Rice and dioscorea fermented with Monascus purpureus NTU 568 have health‐promoting attributes in vitro and in vivo . The aim of this study was to investigate the immunomodulatory and antioxidant effects of polysaccharides from red mould rice (RMRP) and red mould dioscorea (RMDP) in Raw 264.7 cells. RESULTS: The results showed the antioxidant capabilities (including scavenging, chelating, inhibition of lipid peroxidation, and reducing power) of RMRP and RMDP at a concentration of 10 mg mL^?1. RMRP and RMDP also stimulated cell proliferation, nitric oxide production, phagocytosis and cytokine production (including IL1‐β, IL‐6 and TNF‐α) in Raw 264.7 cells. CONCLUSION: These findings demonstrate that RMRP and RMDP have antioxidant and immunomodulation potential to be developed as novel dietary supplements. Copyright © 2011 Society of Chemical Industry     

Vitamin B6 suppresses serine protease inhibitor 3 expression in the colon of rats and in TNF-α-stimulated HT-29 cells

Scope: Previous reports in the areas of animal studies and, recently epidemiology, have linked anti‐tumorigenic and anti‐inflammatory effects to dietary vitamin B6. This study investigated the molecular mechanism of these effects of vitamin B6. Methods and results: DNA microarray analysis was used to obtain information on changes in colon gene expression from vitamin B6 (pyridoxine) repletion in vitamin B6‐deficient rats. Pyridoxine supplementation down‐regulated the inflammatory molecule, serine protease inhibitor clade A member 3 (SPI‐3) mRNA expression in the colon. This study also showed that tumor necrosis factor α (TNF‐α) induced SPI‐3 mRNA expression in HT‐29 human colon cancer cells, and vitamin B6 (pyridoxal hydrochloride) pretreatment of HT‐29 cells inhibited TNF ‐induced mRNA expression of SPI‐3. Vitamin B6 inhibited TNF‐α‐induced NF‐κB activation via suppression of IκBα degradation in HT‐29 cells. HT‐29 cells stably expressing epitope‐tagged ubiquitin were generated and vitamin B6 pretreatment was shown to inhibit ubiquitination of the IkB protein in response to TNF‐α‐i. Conclusion: Vitamin B6 suppressed SPI‐3 expression in the colon of rats and in TNF‐α‐stimulated HT‐29 cells. Further, this study showed a possible role of vitamin B6 in the regulation of protein ubiquitination.     

Quercetin,Hyperin, and Chlorogenic Acid Improve Endothelial Function by Antioxidant,Antiinflammatory, and ACE Inhibitory Effects

In recent years, the blueberry cultivation and processing industry developed quickly because blueberries are super‐fruit with healthy function. Blueberry leaves are byproducts of the blueberry industry, which are rich in bioactive phenolics, such as quercetin (Q), hyperin (H), and chlorogenic acid (C). This study investigated protective effects of 3 phenolics (Q, H, and C) from leaves of rabbiteye blueberry Vaccinium ashei on human umbilical vein endothelial cells. The results showed that all these 3 phenolics could improve endothelial function by inhibiting oxidative damage and proinflammatory cytokines caused by tumor necrosis factor‐α (TNF‐α). The cell vitalities of endothelial cells pretreated with Q, H, and C were higher than those stimulated with TNF‐α only. These phenolics could decrease reactive oxygen species and xanthine oxidase‐1 levels and increase superoxide dismutase and heme oxygenase‐1 levels in endothelial cells. They also could decrease the protein expressions of intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, and monocyte chemotactic protein‐1 induced by TNF‐α. In addition, Q, H, and C also exhibited vasodilatory effect by reducing the angiotensin I–converting enzyme (ACE) protein levels in endothelial cells. Mostly 3 phenolics exhibited bioactivities as a function of concentration, but the effects not always depended on the concentration. The antioxidant and antiinflammatory effects of Q seemed to be more pronounced than H; however, H exhibited higher cell vitalities. The results indicated that phenolics from rabbiteye blueberry leaves could be potential antioxidants, inflammation and ACE inhibitors, and rabbiteye blueberry leaves provide a new resources of phytochemicals beneficial for cardiovascular health.     

Red mold dioscorea‐induced G2/M arrest and apoptosis in human oral cancer cells

BACKGROUND: Monascus‐fermented products are among the most commonly used traditional food supplements. Dioscorea is known to exhibit anticancer properties. In this study the effects of the ethanol extract of red mold dioscorea (RMDE) on cell proliferation, cell cycle and apoptosis in human oral cancer cells were investigated. RESULTS: RMDE exercised growth inhibition on squamous cell carcinoma‐25 (SCC‐25) cells. RMDE‐mediated G2/M phase arrest was associated with the down‐regulation of NF‐κB, resulting in the inhibition of cyclin B1 and CDK1 expression; this may be the mechanism by which RMDE inhibits cancer cells. Furthermore, the proapoptotic activity of RMDE was revealed by the Annexin V‐FITC/PI double‐staining assay. In addition, the proapoptotic effect of RMDE was evident by the inhibition of Bax expression in the mitochondria, resulting in the activation of caspase‐9 and caspase‐3 and subsequent triggering of the mitochondrial apoptotic pathway. RMDE also enhanced caspase‐8 activity, indicating the involvement of the death receptor pathway in RMDE‐mediated SCC‐25 cell apoptosis. CONCLUSION: RMDE treatment inhibited the growth of SCC‐25 cells by arresting cell cycle at the G2/M phase and induced apoptosis in a time‐ and dose‐dependent manner. Therefore RMDE may be a good candidate for development as a dietary supplement against oral cancer. Copyright © 2010 Society of Chemical Industry     

Alterations of the Profiles of Iso‐α‐Acids During Beer Ageing,Marked Instability of Trans‐Iso‐α‐Acids and Implications for Beer Bitterness Consistency in Relation to Tetrahydroiso‐α‐Acids

Age‐induced decomposition of iso‐α‐acids, the main bittering principles of beer, determines the consistency of the beer bitter taste. In this study, the profiles of iso‐α‐acids in selected high‐quality top‐fermented and lager beers were monitored by quantitative high‐performance liquid chromatography at various time intervals during ageing. The degradation of the iso‐α‐acids as a function of time is represented by the ratio, in percentage, of the sum of the concentrations of trans‐isocohumulone and trans‐isohumulone to the sum of the concentrations of cis‐isocohumulone and cis‐isohumulone. This parameter is relevant with respect to the evaluation of bitterness deterioration in aged beers. Trans‐iso‐α‐acids having a shelf half‐life of less than one year proved to be significantly less stable than cis‐iso‐α‐acids, but it appears feasible to counteract degradation if a suitable beer matrix is available. The fate of the trans‐iso‐α‐acids in particular adversely affects beer bitterness consistency. In addition to using hop products containing low amounts of trans‐iso‐α‐acids, brewers may profit of the remarkable stability of tetrahydroiso‐α‐acids, even on prolonged storage, for the production of consistently bitter beers.     

Salvianolic acid B inhibits low‐density lipoprotein oxidation and neointimal hyperplasia in endothelium‐denuded hypercholesterolaemic rabbits

BACKGROUND: Atherosclerosis and restenosis are inflammatory responses involving free radicals and lipid peroxidation and may be prevented/cured by antioxidant‐mediated lipid peroxidation inhibition. Salvianolic acid (Sal B), a water‐soluble antioxidant obtained from a Chinese medicinal herb, is believed to have multiple preventive and therapeutic effects against human vascular diseases. In this study the in vitro and in vivo inhibitory effects of Sal B on oxidative stress were determined. RESULTS: In human aortic endothelial cells (HAECs), Sal B reduced oxidative stress, inhibited low‐density lipoprotein (LDL) oxidation and reduced oxidised LDL‐induced cytotoxicity. Sal B inhibited Cu²⁺‐induced LDL oxidation in vitro (with a potency 16.3 times that of probucol) and attenuated HAEC‐mediated LDL oxidation as well as reactive oxygen species (ROS) production. In cholesterol‐fed New Zealand White rabbits (with probucol as positive control), Sal B intake reduced Cu²⁺‐induced LDL oxidation, lipid deposition in the thoracic aorta, intimal thickness of the aortic arch and thoracic aorta and neointimal formation in the abdominal aorta. CONCLUSION: The data obtained in this study suggest that Sal B protects HAECs from oxidative injury‐mediated cell death via inhibition of ROS production. The antioxidant activity of Sal B may help explain its efficacy in the treatment of vascular diseases. Copyright © 2010 Society of Chemical Industry     

Immunomodulatory properties of the milk whey products obtained by enzymatic and microbial hydrolysis

The objective of this study was to investigate the in vitro immunomodulatory effect of milk whey through enzymatic hydrolysis, microbial fermentation and two‐stage hydrolytic reactions (enzymatic and microbial reactions) by analysing cytokine profiles. Results indicated that the milk whey sample fermented by Lactobacillus kefiranofaciens M1 and two‐stage hydrolytic reactions (hydrolysed by Alcalase and then fermented by L. kefiranofaciens M1) could significantly induce the production of tumour necrosis factor (TNF)‐α and IL‐12 compared with the milk whey control and enzymatic treatments. Further characterisation of the immunomodulatory factor by membrane filtration and mutanolysin hydrolysation, the stimulatory activity for IL‐12 and TNF‐α production was found to be reduced and to be correlated positively with the cell wall components in L. kefiranofaciens M1. In addition, Th2‐polarised splenocytes revealed that L. kefiranofaciens M1 had both IL‐12 inducing and IL‐4 repressing activities. These results suggested that L. kefiranofaciens M1 could direct the Th1/Th2 balance toward Th1.     

Effect of fermentation by Bacillus subtilis on antioxidant and cytotoxic activities of black rice bran

Black rice bran was fermented with Bacillus subtilis KU3 isolated from Korean traditional food, Kimchi. Antioxidant and cytotoxic activities of the fermented black rice bran were investigated. Total phenolic and anthocyanin contents decreased from 171.54 mg GAE g^?1 and 2.31 mg g^?1 to 139.13 mg GAE g^?1 and 2.12 mg g^?1, respectively, after fermentation. Antioxidant activities determined by 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging, β‐carotene bleaching and ferric thiocyanate assay were correlated with total phenolic and anthocyanin contents. Non‐fermented black rice bran extract (NFBE) showed greater antioxidant activities than fermented black rice bran extract (FBE). Cytotoxic activities measured by MTT assay showed that both NFBE and FBE had over 50% activities. The cytotoxic activities of FBE against MCF‐7 and HeLa cells were 71.65% and 68.07%, respectively, at 8.0 mg mL^?1, but those of NFBE were lower than 50%. These results suggested that the cytotoxic activity of black rice bran improved through fermentation, while antioxidant activity reduced.     

Volatile compounds isolated from rice beers brewed with three medicinal plants

The volatile compounds and physicochemical properties of rice beers brewed with three medicinal plants, namely Acanthopanax senticosus (Siberian ginseng), Scutellaria baicalensis (baikal skullcap) and Cornus officinalis (Japanese cornel) were analysed. The rice beers were produced and fermented from unhulled ground rice, malt, and medicinal plant extracts. The medicinal plant extracts, used at 5 and 10 % (v/v) were blended with wort before fermentation. Compared with a draft beer fermented without rice, the rice beers had lower levels of pH, acidity, amino acid content and reducing sugars. Of the rice beers, the beer with the addition of 10% Japanese cornel had the highest colour value and foam stability. The volatile compounds of the rice beers were extracted using a solvent‐assisted flavour evaporation apparatus and analysed by gas chromatography–mass spectrometry. The rice beer with 10% Siberian ginseng showed the most diverse volatile profile, in that 54 kinds of volatile compounds were detected. The rice beer with 10% Japanese cornel had the highest relative amount of volatile chemicals of all of the rice beers. Lactones such as γ‐hexalactone, γ‐nonalactone and γ‐decalactone were detected in all of the rice beers. Copyright © 2013 The Institute of Brewing & Distilling     

Salvianolic Acid B Inhibits High‐Fat Diet‐Induced Inflammation by Activating the Nrf2 Pathway

Salvianolic acid B (Sal B) is a major water‐soluble bioactive component of Salvia miltiorrhiza, which is a traditional Chinese medicine. We investigated the ways in which Sal B affects high‐fat diet (HFD)‐induced immunological function disorder remission using a C57BL/6 mouse model. We gave groups of C57BL/6 mice a normal diet (Control), a normal diet supplemented with Sal B (Control + Sal B), a high‐fat diet (HF), and a high‐fat diet supplemented with Sal B (HF + Sal B) for 10 wk. Sal B supplementation decreased the body weight and plasma lipids, increased the fecal excretion of lipids, prevented the accumulation of chronic oxidative stress, and reversed the disproportionality of CD3⁺CD4⁺ and CD3⁺CD8⁺ T lymphocytes compared to HFD. We found an increase in IL‐6 and TNF‐α, while IL‐10 decreased in plasma after the HFD and Sal B reversed the deregulation of the Thl/Th2 ratio. In addition, HFD‐induced inflammation was stopped by Sal B through the downregulation of nuclear factor‐κB (NF‐κB), cyclooxygenase‐2 (COX‐2), and inducible NO synthesis (iNOS), and the upregulation of nuclear factor‐erythroid 2‐related factor 2 (Nrf2)‐regulated genes. These findings demonstrated that Sal B could effectively attenuate inflammation by activating the Nrf2‐mediated antioxidant defense system.     

A 90-D Toxicity Study of Monascus-Fermented Products Including High Citrinin Level

Abstract: Monascus is one of the traditional fermentation fungi and has been used in many kinds of food for thousands of years. Although Monascus-fermented red mold rice performs cholesterol-lowering effects, blood pressure-lowing effects, and antioxidant effects, another metabolite, nephrotoxic and hepatotoxic citrinin, causes the concerns for safety. Various citrinin concentrations (1, 2, 10, 20, and 200 ppm) in the red mold rice are, respectively, estimated for safe use in animal tests. According to the results of serum biochemistry assays of liver and kidney in each group, citrinin did not reveal any nephrotoxicity and hepatotoxicity. Furthermore, the results of histopathological slices of liver and kidney in each group did not show any significant differences from control histopathological findings. As a result, we presume that citrinin concentrations in Monascus-fermented products within 200 ppm will not affect the functions of liver and kidney or cause any nephrotoxicity and hepatotoxicity. According to safety factor, it is proposed that 2 ppm citrinin in Monascus-fermented products may be a safe concentration.     

Effect of fermentation metabolites on rheological and sensory properties of fermented rice noodles

BACKGROUND: Considering the effect of natural fermentation on the textural improvement of fermented rice noodles in China and South Asia, and given the lack of reports concerning the roles of fermentation metabolites (enzymes, organic acids, glucose and maltose), this study aims to determine fermentation metabolites produced during fermentation of raw milled rice grains, and investigate their effects on rheological and sensory properties of rice noodles. RESULTS: α‐Amylase activity was correlated with reducing sugar content significantly in the supernatant during fermentation process (r = 0.76, P < 0.05). Lactic acid was the dominant organic acid produced by fermentation. Protein and lipid content decreased significantly by fermentation. Treating the rice grains with trypsin, lipase or lactic acid could modify the rheological characteristics and improve the sensory properties of rice noodles. Removal of protein and lipid by physical extraction confirmed the results. The residue of glucose and maltose in rice flour weakened the noodle texture. CONCLUSIONS: Fermentation of raw milled rice decreased protein and lipid content, increased the purity of rice starch, and thus improved the texture of fermented rice noodles. The low molecule weight sugars produced during fermentation should be removed for their negative effect on texture. Copyright © 2008 Society of Chemical Industry     

Enhancement of urea uptake in Chinese rice wine yeast strain N85 by the constitutive expression of DUR3 for ethyl carbamate elimination

Most of the fermented alcoholic beverages, particularly Chinese rice wine, contain the potentially human carcinogenic compound ethyl carbamate (EC). As a major EC precursor in Chinese rice wine, urea in fermentations can be transported into the yeast cell by urea permease and finally metabolized by urea carboxylase and allophanate hydrolase in vivo. To eliminate EC in Chinese rice wines, the present study constructed high urea uptake yeast strains N1‐D, N2‐D and N‐D, by introducing a strong promoter (PGK1p) into the urea permease gene (DUR3) of the industrial Chinese rice wine yeast N85, and by the restoration of the URA3 gene at the same time. With these self‐cloned, high urea uptake strains, the urea and EC in the terminal Chinese rice wine samples were reduced to different extents. With two copies of overexpressed DUR3, the N‐D strain could reduce the urea and the EC by 53.4 and 26.1%, respectively. No difference in fermentation characteristics was found between the engineered strains and the parental industrial yeast strain N85. These results could help to optimize the genetic manipulation strategy for EC elimination in Chinese rice wine production. Copyright © 2015 The Institute of Brewing & Distilling