syringin and Inflammation

Asthma is an allergic chronic inflammatory disease of the pulmonary airways, characterized by the infiltration of white blood cells and release of inflammatory cytokines of complex pathways linked to its pathogenesis. Syringin extracted from various medicinal plants has been used extensively for the treatment of inflammatory diseases. Hence, this study was conducted to further explore the protective effects of the syringin in ovalbumin (OVA) induced-asthma mice model. OVA-sensitized BALB mice were treated intraperitonealy with three doses (25, 50 and 100 mg/kg) of the syringin which was validated by the alteration in the immunoglobulin E (IgE) levels, cytokines levels, histopathological evaluation inflammatory cell count, lung weight, nitrite (NO) levels, oxidative stress biomarkers and gene markers. The treatment of syringin intensely reduced the increased IgE, inflammatory cytokines, WBC count and restored the antioxidant stress markers OVA stimulated animals. In addition, a significant reduction in inflammation and mucus production was evidenced in histopathological analysis which was further validated by suppression NF-κB pathway activation by syringin. These results suggest that syringin may improve asthma symptoms in OVA-induced mice by modulating NF-κB pathway activation.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Cytokines; Disease Models, Animal; Female; Glucosides; Inflammation; Lung; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Phenylpropionates; Pneumonia; Signal Transduction

Inflammatory bowel disease (IBD) is a chronic inflammatory condition with high incidence. Syringin exhibits multiple pharmacological properties, including anti-inflammatory effects. However, the effect of syringin on inflammation of IBD is still unclear. Here, the dextran sulfate sodium (DSS)-induced colitis model was established in vivo. Rat intestinal epithelium IEC6 cells were treated with lipopolysaccharide (LPS) in vitro. Syringin inhibited DSS or LPS-induced overproduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and proinflammatory substances (iNOS, COX-2). Moreover, syringin inactivated the proinflammatory NF-κB p65 pathway by decreasing IκBα phosphorylation at Ser 32. The activation of antioxidant Nrf2 signaling pathway was promoted by syringin. Additionally, LPS-induced inflammation in IEC6 cells was also suppressed by NF-κB inhibitor PDTC and Nrf2 activator RTA408. The anti-inflammatory effects of syringin were comparable to these two reagents. Taken together, our results suggest that syringin shows protective effects on intestinal inflammation through inhibiting NF-κB, while activating Nrf2 signaling pathway in colitis.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Colitis; Cytokines; Glucosides; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Lipopolysaccharides; Mice, Inbred BALB C; NF-E2-Related Factor 2; NF-kappa B; Phenylpropionates; Rats

Gestational diabetes (GDM) is common in pregnancies due to the inflammation and oxidative stress-mediated insulin resistance. In the present study, GDM was induced in the Wistar rats by administering the streptozotocin to elucidate whether the administration of syringin (50 mg/kg/day) during pregnancy could improve maternal glycemia and protect against the complications of GDM. The animals were assessed for their morphological changes in the β-islets of Langerhans and their insulin-producing ability, inflammatory cytokine markers, and the involvement of TLR4/MyD88/NF-κB signaling pathway using RT-PCR. The results demonstrated that the onset of GDM demonstrated pancreatic tissue degeneration in the islets of Langerhans with a significant increase in oxidative stress and reduced antioxidant enzymes. Besides, the mRNA expression levels of TLR4, MyD88, NF-Kβ p65; NLRP3 mRNA were profoundly increased in GDM rats compared to normal pregnant rats. On the other hand, syringin administered GDM rats abrogated the oxidative stress and attenuated the level of the inflammatory cytokines. Intriguingly, the decrease in TLR4 expression and the downstream molecules of MyD88, NF-κB, and NLRP3 were also observed in syringin administered GDM rats that indicate the insulin secretion stimulatory actions of syringin through the suppression of TLR4 signaling. These novel findings of the study provide evidence that syringin could be a probable candidate to be used in the treatment of gestational diabetes in the future.

Topics: Animals; Animals, Newborn; Cytoprotection; Diabetes, Gestational; Eleutherococcus; Female; Glucosides; Inflammation; Male; Myeloid Differentiation Factor 88; NF-kappa B; Oxidative Stress; Phenylpropionates; Pregnancy; Rats; Rats, Wistar; Signal Transduction; Toll-Like Receptor 4

In the treatment of type 2 diabetes, improvements in glucose control are often linked to side effects such as weight gain and altered lipid metabolism, increasing the risk of cardiovascular disease. It is therefore important to develop antidiabetic drugs that exert beneficial effects on insulin sensitivity and lipid metabolism at the same time. Here we demonstrate that syringin, a naturally occurring glucoside, improves glucose tolerance without increased weight gain in high-fat diet-induced obese mice. Syringin augmented insulin-stimulated Akt phosphorylation in skeletal muscle, epididymal adipose tissue (EAT), and the liver, showing an insulin-sensitizing activity. Syringin-treated mice also showed markedly elevated adiponectin production in EAT and suppressed expression of pro-inflammatory cytokines in peripheral tissues, indicating a significant reduction in low-grade chronic inflammation. Additionally, syringin enhanced AMP-activated protein kinase activity and decreased the expression of lipogenic genes in skeletal muscle, which was associated with reduced endoplasmic reticulum (ER) stress. Taken together, our data suggest that syringin attenuates HFD-induced insulin resistance through the suppressive effect of adiponectin on low-grade inflammation, lipotoxicity, and ER stress, and show syringin as a potential therapeutic agent for prevention and treatment of type 2 diabetes with low risk of adverse effects such as weight gain and dysregulated lipid metabolism.

Topics: Adiponectin; Animals; Diet, High-Fat; Endoplasmic Reticulum Stress; Glucose Tolerance Test; Glucosides; Inflammation; Injections, Intraperitoneal; Insulin Resistance; Male; Mice; Mice, Obese; Phenylpropionates

One new octulosonic acid derivative, chrysannol A (1), along with 17 known compounds (2-18), were isolated from Chrysanthemum indicum flowers. Their structures were determined from 1D NMR, 2D NMR, HR-ESI-MS spectral data, and comparisons with previous reports. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compound 8 showed the highest inhibition of NO production of 46.09% at a concentration of 10.0μM. Compounds 7, 10, 11, and 16 inhibited TNF-α secretion at all concentration tested (0.4, 2.0, and 10.0μM), with inhibition values ranging from 22.27% to 33.13%. In addition, compound 8 and 9 decrease COX-2 and iNOS protein on Western blot analysis in dose dependent manner.

Topics: Anti-Inflammatory Agents; Cells, Cultured; Chrysanthemum; Cyclooxygenase 2; Flavonoids; Flowers; Inflammation; Lipopolysaccharides; Macrophages; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II; Phytotherapy; Plant Extracts; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship; Tumor Necrosis Factor-alpha

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature