Oxidative stress and neuroinflammation are implicated in the development and pathogenesis of Alzheimer’s disease (AD). Here, we investigated the anti-inflammatory and antioxidative effects of krill oil. Oil from Euphausia superba (Antarctic krill), an Antarctic marine species, is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We examined whether krill oil diet (80 mg/kg/day for one month) prevents amyloidogenesis and cognitive impairment induced by intraperitoneal lipopolysaccharide (LPS) (250 µg/kg, seven times daily) injections in AD mice model and found that krill oil treatment inhibited the LPS-induced memory loss. We also found that krill oil treatment inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreased reactive oxygen species (ROS) and malondialdehyde levels. Krill oil also suppresses IκB degradation as well as p50 and p65 translocation into the nuclei of LPS-injected mice brain cells. In association with the inhibitory effect on neuroinflammation and oxidative stress, krill oil suppressed amyloid beta (1–42) peptide generation by the down-regulating APP and BACE1 expression in vivo. We found that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (50 and 100 µM) dose-dependently decreased LPS-induced nitric oxide and ROS generation, and COX-2 and iNOS expression as well as nuclear factor-κB activity in cultured microglial BV-2 cells. These results suggest that krill oil ameliorated impairment via anti-inflammatory, antioxidative, and anti-amyloidogenic mechanisms.
Ultraviolet B (UVB) irradiation causes sunburn, inflammatory responses, dysregulation of immune function, oxidative stress, DNA damage and photocarcinogenesis on skin. Rosemary (Rosmarinus officinalis L.) has been reported to inhibit inflammation. Carnosol, a major component of Rosemary, has prominent anti-inflammatory effects. However, its protective effect on UVB-induced inflammatory skin responses has not yet been reported. Here, we investigated the effectiveness of carnosol on UVB-induced inflammation. We examined the anti-inflammation effect of topical application of carnosol (0.05 µg/cm2) on UVB (540 mJ/cm2, for 3 successive days)-induced skin inflammation in HR1 mice. Topical application of carnosol inhibited UVB-induced erythema, epidermal thickness, inflammatory responses in HR1 mice. Carnosol reduced the level of Immunoglobulin-E and IL-1β in blood serum of UVB-induced mice. Carnosol also significantly inhibited the UVB-induced expression of inflammatory marker protein (iNOS and COX-2) in back skin of mice. In addition, carnosol treated skin decreased activation of STAT3, a transcriptional factor regulating inflammatory genes. Our study suggested that carnosol has protective effects on skin inflammatory skin damages by UVB.
An N-terminus sequence of human interleukin 1beta (hIL-1beta) was used as a fusion expression partner for the production of two recombinant therapeutic proteins, human granulocyte-colony stimulating factor (hG-CSF) and human growth hormone (hGH), using Saccharomyces cerevisiae as a host. The expression cassette comprised the leader sequence of killer toxin of Kluyveromyces lactis, the N-terminus 24 amino acids (Ser5-Ala28) of mature hIL-1beta, the KEX2 dibasic endopeptidase cleavage site, and the target protein (hG-CSF or hGH). The gene expression was controlled by the inducible UAS(gal)/MF-alpha1 promoter. With the expression vector above, both recombinant proteins were well secreted into culture medium with high secretion efficiencies, and especially, the recombinant hGH was accumulated up to around 1.3 g/L in the culture broth. This is due presumably to the significant role of fused hIL-1beta as secretion enhancer in the yeast secretory pathway. In our recent report, various immunoblotting analyses have shown that the presence of a core N-glycosylation resident in the hIL-1beta fragment is likely to be of crucial importance in the high-level secretion of hG-CSF from the recombinant S. cerevisiae. When the N-glycosylation was completely blocked with the addition of tunicamycin to the culture, the secretion of hG-CSF and hGH was decreased to a negligible level although the other host-derived proteins were well secreted to the culture broth regardless of the presence of tunicamycin. The N-terminal sequencing of the purified hG-CSF verified that the hIL-1beta fusion peptide was correctly removed by in vivo KEX2 protease upon the exit of fusion protein from Golgi complex. From the results presented in this article, it is strongly suggested that the N-terminus fusion of the hIL-1beta peptide could be utilized as a potent secretion enhancer in the expression systems designed for the secretory production of other heterologous proteins from S. cerevisiae.
Purpose In our previous study, we demonstrated that both titrated extract of Centella asiatica (TECA) and astaxanthin (AST) have anti-inflammatory effects in a 5% phthalic anhydride (PA) mouse model of atopic dermatitis (AD). The increasing prevalence of AD demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of the ointment form of TECA, AST and a TECA + AST combination in a mouse model of AD to see whether a combination of the reduced doses of 2 compounds could have a synergistic effect. Methods An AD-like lesion was induced by the topical application of 5% PA to the dorsal ear and back skin of an Hos:HR-1 mouse. After AD induction, TECA (0.5%), AST (0.5%) and the TECA (0.25%) + AST (0.25%) combination ointment (20 μg/cm 2 ) were spread on the dorsum of the ear or back skin 3 times a week for 4 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclocxygenase (COX)-2, and nuclear factor (NF)-κB activity. We also measured the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and immunoglobulin E (IgE) in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). Results PA-induced skin morphological changes and ear thickness were significantly reduced by TECA, AST and TECA + AST treatments, but these inhibiting effects were more pronounced in the TECA + AST treatment. TECA, AST and the TECA+AST reatments inhibited the expression of iNOS and COX-2; NF-κB activity; and the release of TNF-α, IL-6 and IgE. However, the TECA+AST treatment showed additive or synergistic effects on AD. Conclusions Our results demonstrate that the combination of TECA and AST could be a promising therapeutic agent for AD by inhibiting NF-κB signaling.
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