Phenethyl isothiocyanate suppresses nitric oxide production via inhibition of phosphoinositide 3‐kinase/Akt‐induced IFN‐γ secretion in LPS‐activated peritoneal macrophages

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is well known to have versatile physiological activities, including chemopreventive effects. On the other hand, its anti‐inflammatory effects are poorly reported. Nitric oxide (NO) is associated with a wide variety of inflammatory diseases. In this study, we investigated the effects of PEITC on NO production in LPS‐activated peritoneal macrophages from ICR mice. The signaling pathway of LPS‐induced NO production was examined using neutralizing antibodies [anti‐interferon (IFN)‐γ and anti‐interleukin (IL‐12)] and specific protein kinase inhibitors, as well as others. The activity of PEITC toward NOx production was assessed in mice that received LPS via intraperitoneal administration. The neutralizing antibody of anti‐IFN‐γ, but not anti‐IL‐12, suppressed LPS‐induced NO production by 90%. LY294002, a specific inhibitor of phosphoinositide‐3‐kinase, suppressed Akt and IFN‐γ mRNA expression up‐regulated by LPS, whereas PEITC exhibited a similar inhibition profile. Furthermore, oral administration of PEITC significantly suppressed the serum concentration of NOx in ICR mice. Our results suggest that PEITC suppresses LPS‐induced NO production via inhibition of Akt activation and the resultant decrease in expression of IFN‐γ. This is one of the first reports to demonstrate a marked anti‐inflammatory effect of PEITC following its oral administration.     

Aromatic‐Turmerone Attenuates LPS‐Induced Neuroinflammation and Consequent Memory Impairment by Targeting TLR4‐Dependent Signaling Pathway

Scope : Curcuma longa (turmeric) is a folk medicine in South and Southeast Asia, which has been widely used to alleviate chronic inflammation. Aromatic‐turmerone is one of the main components abundant in turmeric essential oil. However, little information is available from controlled studies regarding its biological activities and underlying molecular mechanisms against chronic inflammation in the brain. In the current study, we employed a classical LPS model to study the effect and mechanism of aromatic‐turmerone on neuroinflammation. Methods and results : The effects of aromatic‐turmerone were studied in LPS‐treated mice and BV2 cells. The cognitive function assays, protein analyses, and histological examination were performed. Oral administration of aromatic‐turmerone could reverse LPS‐induced memory disturbance and normalize glucose intake and metabolism in the brains of mice. Moreover, aromatic‐turmerone significantly limited brain damage, through inhibiting the activation of microglia and generation of inflammatory cytokines. Further study in vitro revealed that aromatic‐turmerone targeted Toll‐like receptor 4 mediated downstream signaling, and lowered the release of inflammatory mediators. Conclusion : These observations indicate that aromatic‐turmerone is effective in preventing brain damage caused by neuroinflammation and may be useful in the treatment of neuronal inflammatory diseases.     

Role of Aif1 in regulation of cell death under environmental stress in Candida albicans

Apoptosis‐inducing factor (AIF) is a conserved flavoprotein localized in the mitochondria, inducing apoptosis after translocation into the nucleus. However, its role in the important fungal pathogen, Candida albicans, remains to be investigated. In this study, we find that the C. albicans AIF protein Aif1, similar to its homologues in other organisms, is localized at the mitochondria and translocated into the nucleus under apoptosis‐inducing conditions. Moreover, deletion of AIF1 causes attenuated apoptosis in this pathogen under apoptosis‐inducing conditions, such as the treatment of 2 mm H₂O₂, 10 mm acetic acid or 0.08 mg/l caspofungin, and its overexpression enhances this process. Interestingly, treatment with high levels of these agents leads to reversed sensitivity of aif1Δ/Δ and the overexpression strain AIF1ov. In addition, the virulence of C. albicans is not affected by deletion or overexpression of AIF1. Hence, C. albicans Aif1, as a mitochondria‐localized protein, plays a dual role in the regulation of cell death under different concentrations of the stress‐caused agents. Copyright © 2016 John Wiley & Sons, Ltd.     

Diet‐induced obesity regulates the galanin‐mediated signaling cascade in the adipose tissue of mice

Galanin is a neuropeptide that regulates the food intake, neurogenesis, memory, and gut secretion. This study was conducted to evaluate the high‐fat diet (HFD)‐induced regulation of the galanin receptors (GalRs) and the associated signaling molecules in the adipose tissues of mice. Twenty C57BL/6J mice were given either an HFD or a normal diet for 12 wk. The results of the semiquantitative RT‐PCR analyses indicated that the HFD upregulated the expression of GalR1, GalR2, GalR3, resistance to audiogenic seizures, peroxisome proliferator‐activated receptorγ2, adipocyte protein 2, and protein kinase Cδ and downregulated the expression of peroxisome proliferative activated receptor γ coactivator 1α and uncoupling protein 1 in the adipose tissues. The immunoblot results showed that the protein levels of peroxisome proliferator‐activated receptorγ2 and adipocyte protein 2, and the phosphorylation of c‐Raf and extracellular signal‐regulated kinase 1/2 were increased, while the phosphorylation of cyclic adenosine monophosphate‐responsive element‐binding protein, which regulates peroxisome proliferative activated receptor γ coactivator 1α and uncoupling protein 1, was decreased in the epididymal adipose tissues of the HFD‐fed mice. These results suggest the possible association of the galanin‐mediated signaling pathways in the manifestation of the HFD‐induced activation of adipogenesis along with the suppression of thermogenesis in the adipose tissues of mice.     

Role of TNF‐α polymorphism ‐308 in neurosensory irritation

Neurosensory cutaneous discomfort in response to topical products is common, yet the relationship between symptoms such as stinging and visible irritation is currently unclear. The presence of a polymorphism at position ‐308 on the TNF‐α gene has been associated with skin irritation, i.e., erythema, dryness. Individuals with a G to A transition (AA/GA genotypes) have a lower threshold to experimentally induced irritation than those with the wild type (G allele, GG genotype). We investigated the effect of this polymorphism on neurosensory irritation (NSI). DNA genotyping was used to determine the allele type amongst a population of health care workers. The neurosensory response to lactic acid and water on the nasolabial folds and hands was assessed using a quantitative lactic acid sting test. Both genotypes had a more intense response to lactic acid compared with water on the face. The AA/GA genotypes had directionally higher scores from lactic acid (P = 0.1) and significantly higher stinging intensities from water (P = 0.001) on the face. For the hands, stinging intensities were higher for lactic acid and water amongst the AA/GA genotypes (P = 0.03 and 0.006 respectively). NSI to lactic acid was significantly higher on the face than on the hands (P < 0.05). Our findings indicate that subjects with the A transition at position ‐308 on the TNF‐α gene experience more intense NSI with common ingredients, i.e., lactic acid and water, than those with the wild type. TNF‐α polymorphism ‐308 may account for some of the inter‐individual variability in response to skin care practices.