Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways.

Morin, a bioactive flavonoid extracted from the bark of Moraceae plants and many medicinal herbs, has anti-inflammatory and antioxidative effects. In this research, we explored the protective effects of morin against lipopolysaccharide (LPS) and d-galactosamine (D-GalN) induced acute liver injury in mice. Mice were given an intraperitoneal injection of morin before LPS and D-GalN treatment and the HepG2 cells were only given morin to investigate its effects. The results showed that morin markedly inhibited the production of serum alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and hepatic TNF-α, IL-6, and myeloperoxidase (MPO) induced by LPS/D-GalN. In order to evaluate morin effect in the future, we investigated the expression of nuclear factor E2 related factor 2 (Nrf2), nuclear factor-kappaB (NF-κB), toll like receptor 4 (TLR4) on liver injury. Taken together, these results suggested that morin could exert the anti-inflammatory and anti-oxidative effects against LPS/D-GalN-induced acute liver injury by activating Nrf2 signal pathways and inhibiting NF-κB activation.

Cudratricusxanthone A protect pancreatic beta cells from cytokines-mediated toxicity through the inhibition of NF-κB and STAT pathways.

Cudratricusxanthone A (CTXA) has an isoprenylated xanthone skeleton that is known to exert a variety of biological activities, including anti-inflammatory, neuroprotective, hepatoprotective, anti-proliferative, and mono-amine oxidase inhibitory effects. In this study, we investigated the effect of CTXA on IL-1ß (5 ng/ml) and IFN-γ (100 U/ml)-induced ß-cell damage. Pre-treatment with CTXA increased the viability and reactive oxygen species (ROS) inhibition of cytokine-treated RINm5F cells at concentrations of 1-10 µM. CTXA prevented nitric oxide (NO) production, and this effect was correlated with reduced levels of protein and mRNA expression of inducible nitric oxide synthase (iNOS). The molecular mechanism by which CTXA inhibits iNOS gene expression appeared to involve the inhibition of NF-κB activation. Moreover, pancreatic ß-cells treated with cytokines upregulated the phosphorylation of STAT-1, STAT-3 and STAT-5; however, pretreatment with CTXA attenuated these effects. Additionally, in a second set of experiments in which rat islets were used, the protective effects of CTXA in rat islets were essentially the same as those observed when RINm5F cells were used. CTXA prevented cytokines-induced NO production, iNOS expression, JAK/STAT activation, and NF-κB activation and inhibition of glucose-stimulated insulin secretion (GSIS). Collectively, these results suggest that CTXA can be used for the prevention of functional ß-cell damage.

Identification of Bet v 1-related allergens in fig and other Moraceae fruits.

BACKGROUND: Allergy to fig fruit (Ficus carica) has been described in patients allergic to Ficus benjamina or rubber latex but may occur also in pollen-allergic patients. OBJECTIVE: To study the potential cross-reactivity between fig and taxonomically related fruits with the major birch pollen allergen Bet v 1. METHODS: One hundred and eighty-eight patients with or without birch pollen allergy were prick-to-prick tested with fig (F. carica), mulberry (Morus alba), jackfruit (Artocarpus heterophyllus; all family Moraceae) and other pollen-associated foods. Moraceae fruit extracts were separated by SDS-PAGE and tested with patient sera and polyclonal antisera against Mal d 1. Western blot inhibition was performed with Moraceae fruit extracts, birch pollen and recombinant Bet v 1. Putative Bet v 1 homologs in Moraceae fruits were analysed by liquid chromatography-ion trap mass spectrometry. RESULTS: Among 85 patients with isolated birch pollen allergy, 78% had a positive skin test to fresh fig, 10% to dried fig, 91% to mulberry, 91% to jackfruit, 77% to Rosaceae fruits and 83% to hazelnut. Sixty-six per cent of birch pollen-allergic patients positive for fig, reported symptoms after consumption of fresh figs, whereas dried figs were mostly well tolerated. In 60 patients with isolated Ficus benjamina sensitization, the reactivity rates to the same foods were 83-40-0-0-0-0%. None of 32 mugwort pollen-allergic patients reacted to Moraceae fruits. Rabbit anti-Mal d 1 and patient sera reacted to a 17 kDa band in all Moraceae extracts. IgE binding to these proteins was completely inhibited by birch pollen and rBet v 1. Mass spectrometry identified several peptides from the 17 kDa fig, mulberry and jackfruit allergen with respectively 60%, 56% and 76% homology to Bet v 1. CONCLUSION: Fig and other Moraceae fruits contain allergens homologous to Bet v 1 and represent clinically relevant birch pollen-associated foods.

Modulatory effects of phytoglycoprotein (75 kDa) on allergic inflammatory cytokines in Di(2-ethylhexyl) phthalate (DEHP)-stimulated RBL-2H3 cells.

This study investigated the inhibitory effect of a glycoprotein isolated from Cudrania tricuspidata Bureau (CTB glycoprotein) on di(2-ethylhexyl) phthalate (DEHP)-induced mast cell degranulation and related signaling cascade in RBL-2H3 cells. This experiment evaluated the intracellular Ca(2+) level, and the activities of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), transcription factor, and the cytokines in DEHP-treated RBL-2H3 cells. Our results revealed that the CTB glycoprotein in the presence of DEHP inhibits the release of histamine and expression of interleukin (IL)-4, IL-6, and TNF-alpha in RBL-2H3 cells. We also found that the CTB glycoprotein inhibits the intracellular Ca(2+) level, translocation of PKC from cytosol to membrane and the phosphorylation of ERK1/2 in cells. Moreover, the CTB glycoprotein (100 microg/ml) has suppressive effects on transcriptional activation of nuclear factor (NF)-kappaB in DEHP-treated RBL-2H3 cells. The activation of NF-kappaB was collectively blocked by treatment with PKC inhibitor (staurosporine) as well as ERK1/2 inhibitor (PD98059), respectively. The results from these experiments indicated that the CTB glycoprotein inhibits release of histamine and expressions of IL-4, IL-6, and TNF-alpha via down regulations of PKC/MAPK and NF-kappaB on the stage of mast cell degranulation induced by DEHP. Moreover, oral administration of CTB glycoprotein (10-20 mg/kg) inhibited compound 48/80-mediated systemic reaction in mice. In conclusion, we speculated that the CTB glycoprotein might be one component for preparation of health supplements for prevention of allergic immune disorders.