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Bone loss and bone-related disease are associated with the deregulation of osteoclast function, and therefore agents that affect osteoclastogenesis have attracted attention. The purpose of the present study was to discover modified kavalactone analogs as potential anti-osteoclastogenic agents. We assessed the effect of 26 analogs on osteoclast differentiation in vitro. The most potent compound, (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22), suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of RAW264 cells with IC50 values of 4.3 µM. A partial structure-activity relationship study revealed the importance of fluorine and its position within the 5,6-dehydrokawain skeleton. The results of a pit formation assay suggested that compound 22 prevents osteoclastic bone resorption by inhibiting osteoclastogenesis. Moreover, compound 22 downregulated mRNA expression levels of RANKL-induced nuclear factor of activated T cells c1 (NFATc1) and osteoclastogenesis-related genes. These results suggest that (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one scaffold could lead to the identification of new anti-resorptive agents.

Oxidative stress, chronic inflammation, dyslipidemia, hyperglycemia, and shear stress (physical effect) are risk factors associated with the pathogenesis of atherosclerosis. Rice bran, a by-product of rice milling process, is known to house polyphenols and vitamins which exhibit potent antioxidant and anti-inflammatory properties. Through recent emerging knowledge of rice bran in health and wellness, the present study was aimed to assess the ameliorative effects of rice bran extracts (RBE) derived from Japanese colored rice varieties in modulating risk factors of atherosclerosis via in vitro and in vivo study models. Pre-treatment of lipopolysaccharide (LPS)-stimulated murine J774A.1 macrophage-like cells with RBE alleviated nitric oxide (NO) overproduction and downregulated gene expressions of pro-inflammatory modulators: tumor necrosis factor-α (TNF-α), interleukin (IL)-α (IL-1α), IL-1β, IL-6, and inducible nitric oxide synthase (iNOS). In addition, RBE also significantly attenuated LPS-stimulated protein expressions of iNOS, TNF-α, IL-1α, and IL-6 in J774A.1 macrophage-like cells as compared to non-treated LPS control group. In in vivo, 12 weeks of RBE dietary supplementations significantly reduced (p < 0.05) total cholesterol, triglycerides, and pro-atherogenic oxidized LDL/β2-glycoprotein I (oxLDL/β2GPI) complexes at plasma levels, in high fat diet (HFD) induced low density lipoprotein receptor knockout (Ldlr−/-) mice. En face pathological assessments of murine aortas also revealed significant reductions by 38% (p < 0.05) in plaque sizes of RBE-supplemented HFD mice groups as compared to non RBE-supplemented HFD control mice group. Moreover, gene expressions of aortic (iNOS, TNF-α, IL-1β) and hepatic (TNF-α, IL-1α, IL-1β) pro-inflammatory modulators were also downregulated in RBE-supplemented mice groups. Present study has revealed the potent health attributes and application of RBE as a dietary supplement to attenuate risks of inadvertent oxidative damage and chronic inflammation underlying the pathogenesis of atherosclerosis. Intrinsically, present preliminary findings may provide global health prospects for future dietary implementation of RBE in management of atherosclerosis., Food science; Food analysis; Rice bran extract (RBE); Functional food; Phytochemicals; Atherosclerosis; Oxidative stress; Inflammation; Antioxidant; Anti-inflammation; Oxidized lipoprotein (oxLDL).

Obesity is a risk factor for many diseases, including type 2 diabetes and cardiovascular disease, and is related to the rising morbidity and mortality. Discovery of agents targeting adipogenesis, especially from natural sources, is important for the treatment of obesity. Here, we aimed to identify anti-adipogenic substances in methanol extracts of Physalis peruviana and to investigate their effect, along with underlying mechanisms. Activity-guided fractionation of the extract revealed 4β-hydroxywithanolide E (HWE) and withanolide E (WE) as the adipogenesis inhibitors. Both compounds suppressed mRNA expression of central adipogenic transcription factors, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer-binding protein α in the early stage of adipocyte differentiation. The inhibitory action of these two withanolides on adipogenesis was largely limited to this stage. The proliferation of preadipocytes was markedly suppressed by treatment with HWE and WE for 24 and 48 h in the differentiation medium, and cell-cycle arrest in the G0/G1 phase was observed. Therefore, our results suggested that withanolides from P. peruviana to be novel anti-adipogenic compounds that modulate mitotic clonal expansion.

As a Japanese folk medicine, Tithonia diversifolia is used for cardiovascular disease prevention and health maintenance. We isolated T. diversifolia-derived orizabin based on the nitric oxide production inhibitory effect. This study aimed to consider orizabin as a novel functional compound with anti-atherosclerotic activity. Orizabin significantly inhibited the adhesion of THP-1 cells to human umbilical vein endothelial cells (HUVECs) and suppressed the mRNA expression of adhesion molecules in HUVECs. In Phorbol 12-myristate 13-acetate stimulated THP-1 cells, orizabin suppressed macrophage differentiation, CD36 expression (1% at 10 μM), and NFκB transcriptional activity. Furthermore, orizabin suppressed oxidized low-density lipoprotein (oxLDL) uptake in macrophages and the Akt phosphorylation. On the contrary, we revealed that phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) mRNA and protein expression were promoted significantly by orizabin (mRNA, 270-fold at 10 μM). Our study presented the possibility that T. diversifolia-derived orizabin is novel anti-atherosclerotic compound via the suppression of Akt phosphorylation, and T. diversifolia may be effective as a new crop for vascular health maintenance. PRACTICAL APPLICATIONS: In this study, the differentiation of monocytes was suppressed without any toxicity, it was obvious in the image, and the oxLDL uptake in monocytes was clearly suppressed by orizabin. Our findings presented that T. diversifolia-derived compound orizabin specifically contributes to the promotion of PTEN expression and suppression of Akt signal in cells, and acts to suppress inflammation by suppression of NFκB transcriptional activity. As a component derived from food, it has a strong function and can be used to maintain the health for blood vessels. It is also a finding that deserves to expand production currently being carried out on a small scale. Furthermore, the promoting effect of PTEN known as a cancer suppressor in orizabin may result in further use for pharmaceuticals research. Orizabin can be safely used as a food-derived compound for maintaining human health.

Some β-glucans have attracted attention due to their functionality as an immunostimulant and have been used in processed foods. However, accurately measuring the β-glucan content of processed foods using existing methods is difficult. We demonstrate a new method, the Sodium hypochlorite Extracting and Enzymatic Digesting (SEED) assay, in which β-glucan is extracted using sodium hypochlorite, dimethyl sulfoxide, and 5 mol/L sodium hydroxide and then digested into β-glucan fragments using Westase which is an enzyme having β-1,6- and β-1,3 glucanase activity. The β-glucan fragments are further digested into glucose using exo-1,3-β-d-glucanase and β-glucosidase. We measured β-glucan comprising β-1,3-, -1,6-, and -1,(3),4- bonds in various polysaccharide reagents and processed foods using our novel method. The SEED assay was able to quantify β-glucan with good reproducibility, and the recovery rate was90% for food containing β-glucan. Therefore, the SEED assay is capable of accurately measuring the β-glucan content of processed foods.

An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity. Among the potential analogs we synthesized, (E)-6-(4-Ethylstyryl)-4-methoxy-2H-pyran-2-one (14) and (E)-6-(4-Butylstyryl)-4-methoxy-2H-pyran-2-one (21) both significantly up-regulated Runx2 and Osterix mRNA expression at 10µM. These osteogenic activities could be mediated by bone morphogenetic protein (BMP) and activation of p38 MAPK signaling pathways. Compounds 14 and 21 also inhibited RANKL-induced osteoclast differentiation of RAW264 cells. These results indicated that novel 5,6-dehydrokawain analogs not only increase osteogenic activity but also inhibit osteoclast differentiation, and could be potential lead compounds for the development of anti-osteoporosis agents.

Investigating the degradation mechanism of a polymer electrolyte fuel cell (PEFC) is indispensable for realizing a longer-lasting fuel cell. This report describes the research results that the cathode catalyst after a 9000 h cell operation has been removed to evaluate the O2 reduction reaction (ORR) and H2O2 generation amount during the ORR. First, the power generation performance of the prepared PEFC single cell was measured vs. the elapsed time of the long-term test operated at 80 °C at the constant current density of 200 mA cm−2. After the 9000 h operation, the power generation performance was confirmed to decrease. Subsequently, the cathode material containing the Pt–Co/C and the ionomer was removed from the cell and packed into the microcavity of the porous microelectrode (PME). By using the PME, ex situ electrochemical measurements were done in a sulfuric acid solution. The background cyclic voltammogram current of the 9000 h sample was one order of magnitude lower than that of the 0 h sample, suggesting that the electrochemical surface area had decreased. The diffusion-limiting ORR current decreased after the endurance test, however, the Tafel slopes were the same between the two in the same electrode potential region. This revealed that the endurance test does not affect the electron transfer mechanism of the ORR. By using the scanning electrochemical microscopy (SECM), the H2O2 yield assessed for the 9000 h sample at 0–0.7 V vs. RHE during the ORR was found to be 3–4 times higher than that for the 0 h sample. Based on the TEM observation, the high H2O2 yield after the 9000 h operation was considered to be due to the degradation of the ionomer incorporated in the cathode layer with the Pt–Co/C catalyst.

A long-term operation test of PEFCs was conducted for single cells having an effective area of 25 cm2. The decay rate of the cell voltage was relatively large in the beginning, decreased to about 4 µV h−1 from 3000 to 6000 h, and about 7 µV h−1 in the later stage from 9000 to 12000 h. In order to clarify the cause of the voltage decay, materials composing membrane electrode assembly (MEA) were analyzed by disassembling a cell every 3000 h. After operation, changes of materials, such as particle size change of Pt-Co cathode catalyst, loss of ionomer layers on Pt-Co/C, decrease in thickness of the polymer electrolyte membrane, pore size changes of the cathode, were observed. Electrochemical active surface area of the electrode showed a decreasing tendency. Based on these results, we focused on the improvement of cathode, and developed a “four-layer electrode catalyst” which consisted of Pt-Co alloy particle, carbon support, ionomer and fluorocarbon resin. A test cell using this new type cathode exhibited better performances than a cell using conventional cathode in the durability test under low humidity or low temperature conditions.

Water management of the catalyst layer in a polymer electrolyte membrane fuel cell was improved by focusing on the three-phase boundary. To fabricate the cathode catalyst layer, carbon-support with catalyst and fluorine resin were mixed and heat-treated at the melting temperature of fluorine resin. The transmission electron microscopy images of this electrode catalyst showed that the surfaces of the catalyst particle and of the carbon-support were partly coated by thin film of melted fluorine resin. Ionomer electrolyte material was added to this electrode catalyst, and an electrode catalyst with a four-layer structure was fabricated. The durability at 50°C of a single cell using the four-layer electrode catalyst as the cathode was examined. The deterioration rate was lower than that using the conventional three-layer electrode catalyst. In addition, a load change test at 50°C, an OCV test at 50°C, and a durability test at room temperature gave good results.

Three-body ionic-recombination reactions of Xe+/Br−/He leading to XeBr* excimers and their predissociation products (Xe* and Br*) have been studied by observing emission spectra in a He flowing afterglow. The branching ratios of XeBr(B):XeBr(D):Xe(6s 3P1,6p 1D2):Br(5p) in the Xe+(2P1/2)/Br−/He reaction are 0.65:0.077:0.087:0.19, while those of XeBr(B):XeBr(C):XeBr(D):Xe(6s 3P1):Br(5s) in the Xe+(2P3/2)/Br−/He reaction are 0.87:0.12:0.0040:0.0014:0.0067, respectively. The large relative formation rate of XeBr(B) in the Xe+(2P1/2)/Br−/He reaction indicated that a breakdown of the ion configuration of Xe+ occurs significantly in the Xe+(2P1/2) reaction. The XeBr(B) state is probably formed through multiple collisions with third-body He atoms, which cause a trajectory change from the entrance V[Xe+(2P1/2),Br−] potential to exit V[Xe+(2P3/2),Br−] ionic potentials via predissociation V(Xe*,Br) potentials. The large relative formation rates of XeBr(B,C) in the Xe+(2P3/2)/Br−/He reaction indicated that the ion co...

Thermochromism was observed for an aqueous solution containing zinc(II) and mercury( II) cations and N-p-nitrobenzyl-5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin anion (NO2Bz(Htpps)4-) in the temperature range 10 to 70 °C. The equilibrium constants and the thermodynamic parameters of Zn(NO2Bztpps)3- and Hg(NO2Bztpps)3- have been determined spectrophotometrically to elucidate the thermochromism at 10, 15, 20, 25 and 30 °C in 0.1 mol dm-3 NaNO3. The protonation and metalation constants of NO2Bz(Htpps)4- are defined as K2 = [H2P][H+]-1[HP]-1, K3 = [H3P][H+]-1[H2P]-1 and KMP = [M P][H+][M2+]-1[HP]-1, where HP and MP denote the free base form of the prophyrin and the metalloporphyrins of zinc(II) and mercury(II), respectively. Charges of the prophyrin and metalloporphyrins are omitted for simplicity. The following values were found: logK2 = 7.75 ±0.02 (25 °C), ΔH°/kJmol-1 = -21.2±0.5 and ΔS°/Jmol-1K-1 = 77±1, logK3 = 2.55±0.02 (25 °C), ΔH°/kJmol-1 = -25±0.8 and ΔS°/Jmol-1K-1 = -35±3 and log KZnP = 0.63±0.03 (25 °C), ΔH°/kJmol-1 = 31.0±0.8 and ΔS°/Jmol-1K-1 = 116±3, logKHgP = 6.22±0.03 (25 °C), ΔH°/kJmol-1 = 4.5±0.7 and ΔS°/Jmol-1K-1 = 134±2. The distribution curve calculated from the thermodynamic parameters sufficiently agrees with the observed metal exchange reaction between the metalloporphyrins.

Nascent vibrational distributions of KrF(B) and XeCl(B) resulting from Kr+(2P3/2)+SF−6 and Xe+(2P3/2)+Cl−+He reactions have been determined by a spectral simulation of the bound–free B–X transition. The vibrational distribution of KrF(B) has a maximum at v’=0 and decreases exponentially with increasing v’. It is in reasonable agreement with the statistical prior distribution in which all vibrational and rotational degrees of freedom in the products are taken into consideration. It is therefore concluded that the Kr+(2P3/2)+SF−6 reaction proceeds through a long‐lived [Kr+(2P3/2)SF−6] intermediate. The vibrational distribution of XeCl(B) decreases linearly with increasing v’. It is more vibrationally excited than the prior distribution, indicating that a (Xe+Cl−He) intermediate decomposes before a complete energy randomization. The average fractions of total available energy deposited into vibrational energy of the excimer 〈fv〉 are estimated to be 5.8% for the Kr+(2P3/2)+SF−6 reaction and 16% for the Xe+(2P...

The three‐body ionic‐recombination reaction of Ar+(2P3/2)/Cl−/Ar leading to ArCl(B,C), Ar(3P2), and Cl(4s,4s’,4p,4p’,4d,5p,6s) has been studied spectroscopically in an Ar flowing afterglow. The results obtained are compared with our previous data for the Ar+(2P3/2)/Cl−/He reaction in order to examine the effects of the third‐body atom. The Ar+(2P3/2)/Cl−/Ar reaction populates lower energy states of [Ar+(2P3/2)Cl−] intermediates than the Ar+(2P3/2)/Cl−/He one, so that the branching ratio of excimer becomes large in comparison with those of predissociation channels, the lower ArCl(B) state is preferentially excited than the ArCl(C) state, the ArCl(B) state is populated in lower vibrational levels, and the electronic state distribution of Cl* shifts to lower energy. On the basis of these findings, it is concluded that the heavy Ar atom is a more efficient acceptor of the excess energy than the light He atom in the Ar+(2P3/2)/Cl−/Rg (Rg=rare gas) system.

When the polymer electrolyte membrane fuel cell is operated for a long period of time, there is a change in the material composition of the membrane electrode assembly (MEA) that coincides with progressive deterioration of the cell. Therefore, it is important to analyze the change in MEA composition. In this study, the durability of a fuel cell was examined during a period of 12 000 h. These test cells were disassembled one after another, approximately every 3000 h, and the change in the constituent was analyzed in detail on the view point of the material and structure. The change in the constituent with MEA in relation with the operating time was also analyzed in detail. The relationship between the changes in the constituent and the operating time was examined and clarified. These changes were in the porosity of the electrode, in the pore distribution of the electrode, and in the surface area of the electrode. Moreover, the change in the thickness of the electrolyte membrane and the change in the materi...

The use of auxiliary power and the cost of using main power decrease when the reactive gas is applied at low humidity for the operation of polymer electrolyte membrane fuel cells. The electrolyte membrane and the three-phase boundary of the electrode need to be improved to maintain this low humidity. We carried out a study of the electrode catalyst at low humidity in order to improve the cathode catalyst. Carbon support with a catalyst and fluorocarbon resin were mixed and then were treated at the melting temperature of fluorocarbon resin to fabricate the cathode-electrode catalyst layer. The transmission electron microscopy images of this electrode catalyst revealed that the surfaces of the catalyst particle and the carbon support were partly coated with a thin film of melted fluorocarbon resin. Ionomer electrolyte material was added to this electrode catalyst, and an electrode catalyst with a four-layer structure was fabricated. The durability of this four-layer electrode catalyst being operated at low ...