nothofagin and Disease-Models--Animal

Mast cells play a major role in immunoglobulin E-mediated allergic inflammation, which is involved in asthma, atopic dermatitis, and allergic rhinitis. Nothofagin has been shown to ameliorate various inflammatory responses such as the septic response and vascular inflammation. In this study, we assessed the inhibitory effect of nothofagin on allergic inflammation using cultured/isolated mast cells and an anaphylaxis mouse model. Nothofagin treatment prevented histamine and β-hexosaminidase release by reducing the influx of calcium into the cytosol in a concentration-dependent manner. Nothofagin also inhibited the gene expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-4 by downregulating the phosphorylation of Lyn, Syk, Akt and nuclear translocation of nuclear factor-κB. To confirm these effects of nothofagin in vivo, we used a passive cutaneous anaphylaxis mouse model. Topical administration of nothofagin suppressed local pigmentation and ear thickness. Taken together, these results suggest nothofagin as a potential candidate for the treatment of mast cell-involved allergic inflammatory diseases.

Topics: Anaphylaxis; Animals; Calcium; Cell Degranulation; Chalcones; Cytokines; Disease Models, Animal; Gene Expression Regulation; Hypersensitivity; Inflammation; Male; Mast Cells; Mice, Inbred ICR; NF-kappa B; Rats, Sprague-Dawley

Aspalathin (Aspt) and nothofagin (Not) were reported to have antioxidant activity and are the two major active dihydrochalcones in green rooibos. This study was conducted to determine whether Asp and Not can modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms.. The potential of Aspt and Not treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessing blood urea nitrogen (BUN), serum creatinine, total urine protein, levels of lactate dehydrogenase (LDH), nitric oxide (NO), tumour necrosis factor (TNF)-α, interleukin (IL)-6, and myeloperoxidase (MPO), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity.. Treatment with Aspt and Not decreased plasma levels of BUN, creatinine, urine protein, and LDH in mice with CLP-induced renal damage. Moreover, Aspt and Not inhibited nuclear factor (NF)-κB activation and reduced the induction of NO synthase and excessive production of nitric acid. Aspt and Not treatment also reduced the plasma levels of NO, TNF-α, IL-6, and MPO and reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defence system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in the kidney tissues.. Our results suggest that Aspt and Not protect mice against sepsis-triggered renal injury.

Topics: Animals; Aspalathus; Chalcones; Disease Models, Animal; Human Umbilical Vein Endothelial Cells; Humans; Kidney; Male; Mice; Mice, Inbred C57BL; Protective Agents; Sepsis

The ubiquitous nuclear protein, high mobility group box 1 (HMGB1), is released by activated macrophages and human umbilical vein endothelial cells (HUVECs) and functions as a late mediator of experimental sepsis. Aspalathin (Asp) and nothofagin (Not), which have been reported to have anti-oxidant activity, are the two major active dihydrochalcones found in green rooibos. In this study, we investigated the antiseptic effects and underlying mechanisms of Asp and Not against HMGB1-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of Asp and Not were determined by measuring permeability, monocyte adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. According to the results, Asp and Not effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, Asp and Not suppressed the production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), the activation of nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases 1 and 2 (ERK1/2) by HMGB1. Collectively, these results indicate that Asp and Not could be potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Aspalathus; Chalcones; Disease Models, Animal; HMGB1 Protein; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-6; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Phytotherapy; Sepsis; Signal Transduction; Tumor Necrosis Factor-alpha