Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells

Abstract

Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation. Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. The pharmacological actions of these flavonoids suggest their potential activity for treatment of allergic inflammatory diseases through the down-regulation of mast cell activation.

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

“…COX-2 and iNOS exert a prominent role under inflammatory conditions by producing prostaglandins and NO · , respectively [29,30] . Thus, the antiinflammatory effect of quercetin and rutin in CCl 4 -injured liver could be attributed to the inhibition of the NF-κB pathway, which is in agreement with previous findings [31] . Additionally, the increased NO · synthesis and superoxide generation could result in the formation of peroxynitrite [32] and nitration of protein tyrosine residues [33] , which actively contribute to the development of hepatic necrosis [34] .…”

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

“…Many previous findings have demonstrated that quercetin can inhibit degranulation in various types of mast cells, including rat peritoneal [33] and intestinal mast cells [6] , RBL-2H3 cells [34] , human mast cell lines [35,36] and human basophils [37] . A previous in vivo study indicated that the antioxidant activity of quercetin prevents docetaxel-induced testicular damage in rats.…”

Anti-Inflammatory Effects of an Ethanol Extract of Angelica gigas in a Carrageenan-Air Pouch Inflammation Model

“…Unexpectedly, however, the increased iL-6 content was not affected by pretreatment with EAG. iL-6 plays important roles in acute phase reactions [14,40] and immune responses, especially in autoimmune diseases, as it enhances B lymphocyte differentiation and immunoglobulin production, including igE [35,40]. Thus, it appears that EAG selectively affects inflammatory cells, particularly these cells' cytokine production.…”