Aqueous Extract from Leaves of Citrus unshiu Attenuates Lipopolysaccharide-Induced Inflammatory Responses in a Mouse Model of Systemic Inflammation.

Inflammation is related to various life-threatening diseases including cancer, neurodegenerative diseases, and metabolic syndrome. Because macrophages are prominent inflammatory cells, regulation of macrophage activation is a key issue to control the onset of inflammation-associated diseases. In this study, we aimed to evaluate the potential anti-inflammatory activity of Citrus unshiu leaf extract (CLE) and to elucidate the mechanism underlying its anti-inflammatory effect. We found the inhibitory activity of CLE on the secretion of proinflammatory cytokines and a chemokine from mouse macrophage-like RAW 264.7 cells and mouse peritoneal macrophages. The inhibitory activity of CLE was attributed to downregulated JNK, p38 MAPK, and NF-κB signaling pathways, leading to suppressed gene expression of inflammation-associated proteins. Oral administration of CLE significantly decreased the serum level of proinflammatory cytokines IL-6 and TNFα and increased that of anti-inflammatory cytokine IL-10 in lipopolysaccharide-induced systemic inflammation mice. In addition, oral administration of CLE decreased secretion and gene expression of several proinflammatory proteins in the liver and spleen of the model mice. Overall results revealed that C. unshiu leaf is effective to attenuate inflammatory responses in vitro and in vivo.

Isolation and Characterization of Neuroprotective Components from Citrus Peel and Their Application as Functional Food.

The elderly experience numerous physiological alterations. In the brain, aging causes degeneration or loss of distinct populations of neurons, resulting in declining cognitive function, locomotor capability, etc. The pathogenic factors of such neurodegeneration are oxidative stress, mitochondrial dysfunction, inflammation, reduced energy homeostatis, decreased levels of neurotrophic factor, etc. On the other hand, numerous studies have investigated various biologically active substances in fruit and vegetables. We focused on the peel of citrus fruit to search for neuroprotective components and found that: 1) 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) and auraptene (AUR) in the peel of Kawachi Bankan (Citrus kawachiensis) exert neuroprotective effects; 2) both HMF and AUR can pass through the blood-brain barrier, suggesting that they act directly in the brain; 3) the content of AUR in the peel of K. Bankan was exceptionally high, and consequently the oral administration of the dried peel powder of K. Bankan exerts neuroprotective effects; and 4) intake of K. Bankan juice, which was enriched in AUR by adding peel paste to the raw juice, contributed to the prevention of cognitive dysfunction in aged healthy volunteers. This review summarizes our studies in terms of the isolation/characterization of HMF and AUR in K. Bankan peel, analysis of their actions in the brain, mechanisms of their actions, and trials to develop food that retains their functions.

Auraptene/Naringin-Rich Fruit Juice of Citrus kawachiensis (Kawachi Bankan) Prevents Ischemia-Induced Neuronal Cell Death in Mouse Brain through Anti-Inflammatory Responses.

Cerebral ischemia/reperfusion leads to delayed neuronal cell death, resulting in brain damage. Auraptene (AUR) and naringin (NGIN), which exert neuroprotective effects in ischemic brain, are abundant in the peel of Citrus kawachiensis. Although parts of AUR/NGIN are transited from the peel to the juice during the squeezing of this fruit, these amounts in juice might be too low to exert effects. We thus prepared the AUR/NGIN-rich fruit juice of C. kawachiensis by addition of peel paste to the raw juice. The present study revealed that orally administration of the dried powder of this AUR/NGIN-rich fruit juice (2.5 g/kg/d) for 7 d to ischemic mice significantly suppressed the ischemia-induced neuronal cell death in the hippocampus, which was coincidently with the reduction of hyperactivation of microglia and astrocytes. These results suggest that AUR/NGIN-rich juice of C. kawachiensis may possess therapeutic potential for the prevention of neurodegenerative diseases via inhibition of inflammatory processes.

Citrus kawachiensis Peel Powder Reduces Intestinal Barrier Defects and Inflammation in Colitic Mice.

The anti-inflammatory effect of Citrus kawachiensis peel powder was examined in a murine model of dextran sodium sulfate (DSS)-induced colitic mice. In addition to the whole powder, its ethanol extract rich in polyphenolic compounds and ethanol extraction residue rich in dietary fibers were used. The whole powder ameliorated the DSS-induced body weight loss (body weight changes on day 9, Control 108 ± 2, DSS 91 ± 4, DSS+whole peel powder 106 ± 1%, p < 0.05), colon shortening (colon length, Control 5.0 ± 0.1, DSS 3.9 ± 0.1, DSS+whole peel powder 4.7 ± 0.1 cm, p < 0.05), increased expression of pro-inflammatory cytokines (e.g., TNF-α, Control 1.0 ± 0.1, DSS 22.2 ± 5.8, DSS+whole peel powder 4.3 ± 1.5 arbitrary unit, p < 0.05), and decreased expression of colonic tight junctions (TJs) (e.g., occludin, Control 1.00 ± 0.07, DSS 0.21 ± 0.07, DSS+whole peel powder 0.70 ± 0.06 arbitrary unit, p < 0.05). The resolution of abnormalities barring the decreased expression of zonula occludens-2, junctional adhesion molecule-A, and claudin-7 by the extraction residue was comparable to that achieved using the powder (body weight change 107 ± 1%; colon length 4.7 ± 0.1 cm; TNF-α 4.1 ± 0.7; occludin 0.58 ± 0.06 arbitrary unit, p < 0.05). The ethanol extract alone did not have any influence on these abnormalities (body weight change 94 ± 2%; colon length 4.1 ± 0.1 cm; TNF-α 40.5 ± 9.0 arbitrary unit; occludin 0.18 ± 0.02 arbitrary unit, p < 0.05). The powder and ethanol extraction residue, but not ethanol extract, increased fecal acetic acid concentration (Control 4.9 ± 0.6, DSS 5.0 ± 0.9, DSS+whole peel powder 8.8 ± 1.8, DSS+ethanol extract 5.3 ± 0.8, DSS+ethanol extraction residue 12.5 ± 1.1 mmol/L, p < 0.05). Taken together, DFs in the ethanol extraction residue largely contributed to the peel powder-mediated reduction of TJ barrier defect and inflammation in colitic mice.

Wavelet transforms on Gelfand-Shilov spaces and concrete examples.

In this paper, we study the continuity properties of wavelet transforms in the Gelfand-Shilov spaces with the use of a vanishing moment condition. Moreover, we also compute the Fourier transforms and the wavelet transforms of concrete functions in the Gelfand-Shilov spaces.

Biodegradation of biodiesel wash water from a biodiesel fuel production plant.

The objective of this research was the modification of our biodiesel fuel (BDF) production process to make higher quality BDF. The existing process which does not include a water washing process for raw BDF, has the advantage of no wash water discharge, but occasionally the resultant BDF is of lower grade due to residual ingredients. First, we attempted to integrate water washing into the existing process. After being neutralized and washed with H2SO4, the raw BDF was then washed with water equal to 20% of the raw BDF volume. A good separation of BDF and wash water was achieved, and the resultant wash water contained less than 2% methanol. Second, we evaluated biodegradation of the resultant wash water constituents, and 70% of the strains isolated from environmental samples removed 80 to 90% of total organic carbon. Among these, strain No. 20-68 removed both glycerol and methanol in the wash water within 7 days and was identified as Fusarium falciforme, a ubiquitous environmental microorganisms. These results suggest that if the wash water is released to the environments, the effects on environmental microorganisms will be minimal.

Imide-catalyzed oxidation system: sulfides to sulfoxides and sulfones.

A new combination system, the oxidation of sulfides using aqueous NaOCl in the presence of a catalytic amount of imide under two-phase conditions, has been developed. The combination effectively converts various sulfides to the corresponding sulfoxides and sulfones. It was deduced that the imide could react with NaOCl to produce N-chloroimide, which would play roles of both the active oxidizing reagent and phase transfer catalyst.

NMR conformational analysis of biosynthetic precursor-type lipid A: monomolecular state and supramolecular assembly.

The detailed conformational analysis of a single molecule of the tetraacyl biosynthetic precursor-type lipid A and its characteristic supramolecular assembly in aqueous SDS-micelles are described. Regular molecular arrangements were observed by detailed analysis of the NMR spectra of synthetically pure specimens, including regiospecifically 13C-labeled ones. NMR analysis of a biologically inactive precursor-type analogue with four shorter acyl chains demonstrated its conformational flexibility, indicating the importance of hydrophobic interactions for maintaining the conformation of such molecules.

First Total Synthesis of the Re-Type Lipopolysaccharide.

Three sequential efficient glycosylation reactions starting from D-glucosamine were used in the first total synthesis of Escherichia coli Re lipopolysaccharide, which is one of the most simple lipopolysaccharides found on the surface of living bacteria.