Asiaticoside Mitigates the Allergic Inflammation by Abrogating the Degranulation of Mast Cells.

The effects of asiaticoside (AS) on allergic responses mediated by mast cells were investigated. AS showed no obvious cytotoxicity on RPMCs (rat peritoneal mast cells). AS reduced the intracellular calcium in RPMCs and deprived the histamine release and degranulation. AS also decreased the generation of antigen-induced tumor necrosis factor α, interleukin (IL)-4, IL-8, and IL-1ß in RBL-2H3 cells sensitized by IgE. The suppression of AS on pro-inflammatory cytokines was related with the activation of the intracellular FcεRI and the inhibition of the nuclear factor-κB signaling pathway. In addition, AS disabled the phosphorylation of antigen-induced Syk, Lyn, Gab2, and PLCγ1, thus suppressing the downstream Akt phosphorylation and MAPKs pathways. It also increased HO-1 and Nrf2 expression time dependently. In summary, we demonstrate that AS suppresses the allergic inflammation mediated by mast cells and this effect might be mediated by FcεRI-dependent signaling pathways.

Sesamin attenuates mast cell-mediated allergic responses by suppressing the activation of p38 and nuclear factor-κB.

Establishing therapeutic agents for the treatment of allergic diseases is an important focus of human health research. Sesamin, a lignan in sesame oil, exhibits a diverse range of pharmacological properties. However, to the best of our knowledge, the effect of sesamin on mast cell­mediated allergic responses has not yet been investigated. Thus, the aim of the present study was to investigate the effect of sesamin on mast cell­mediated allergic responses and the underlying mechanisms by which it produces this effect. In rats, oral administration of sesamin inhibited passive cutaneous anaphylaxis. Sesamin exposure attenuated immunoglobulin E­induced histamine release from rat peritoneal mast cells, which was indicated to be mediated by the modulation of intracellular calcium. In human mast cells, sesamin reduced the stimulatory effects of phorbol 12­myristate 13­acetate and calcium ionophore A23187 on the production and secretion of pro­inflammatory cytokines, including tumor necrosis factor­α and interleukin­6. The inhibitory effect of sesamin on pro­inflammatory cytokine production was dependent on nuclear factor κ­light­chain­enhancer of activated B cells (NF­κB) and p38 mitogen­activated protein kinase (MAPK). The present study demonstrates that sesamin inhibits mast cell­derived inflammatory allergic reactions by blocking histamine release, and pro­inflammatory cytokine production and secretion. In addition, the findings indicate that the effect of sesamin is mediated by its effect on p38 MAPK/NF­κB signaling. Furthermore, the in vivo and in vitro anti­allergic effects of sesamin reported in the present study suggest that it is a promising therapeutic agent for the treatment of inflammatory allergic diseases.

Ginsenoside Rh2 attenuates allergic airway inflammation by modulating nuclear factor-κB activation in a murine model of asthma.

Allergic asthma is a chronic inflammatory disease that is regulated by coordination of T-helper type 2 cell cytokines and inflammatory signaling molecules. Ginsenoside Rh2 (G-Rh2) is an active component of ginseng with anti-inflammatory and anti-tumor effects. The aim of the present study was to determine the inhibitory effects of G-Rh2 on allergic airway inflammation in a murine model of asthma, in which mice develop the following pathophysiological features of asthma: Increased abundance of inflammatory cells; increased levels of interleukin-4 (IL-4), IL-5 and IL-13; decreased abundance of interferon gamma in the bronchoalveolar lavage fluid and lung tissue; increased total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum; increased airway hyperresponsiveness (AHR); and activation of nuclear factor kappa B (NF-κB) in lung tissue. In the asthmatic mice, administration of G-Rh2 markedly reduced peribronchiolar inflammation, recruitment of airway inflammatory cells, cytokine production, total and OVA-specific IgE levels and AHR. G-Rh2 administration inhibited NF-κB activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation induced by OVA inhalation. These results suggested that G-Rh2 attenuates allergic airway inflammation by regulating NF-κB activation and p38 MAPK phosphorylation. The present study identified the molecular mechanisms of action of G-Rh2, which supported the potential use of G-Rh2 to prevent and/or treat asthma and other airway inflammatory disorders.