tHGA, a geranyl
acetophenone compound originally isolated from a local shrub called Melicope ptelefolia, has been previously reported to prevent
ovalbumin-induced allergic airway
inflammation in a murine model of allergic
asthma by targeting
cysteinyl leukotriene synthesis. Mast cells are immune effector cells involved in the pathogenesis of allergic diseases including
asthma by releasing cysteinyl
leukotrienes. The
anti-asthmatic properties of tHGA could be attributed to its inhibitory effect on mast cell degranulation. As mast cell degranulation is an important event in allergic responses, this study aimed to investigate the
anti-allergic effects of tHGA in cellular and animal models of
IgE-mediated mast cell degranulation. For in vitro model of
IgE-mediated mast cell degranulation, DNP-
IgE-sensitized RBL-2H3 cells were pre-treated with tHGA before challenged with
DNP-BSA to induce degranulation. For
IgE-mediated passive systemic
anaphylaxis, Sprague Dawley rats were sensitized by
intraperitoneal injection of DNP-
IgE before challenged with
DNP-BSA. Both in vitro and in vivo models showed that tHGA significantly inhibited the release of preformed mediators (β-
hexosaminidase and
histamine) as well as de novo mediators (
interleukin-4, tumour
necrosis factor-α,
prostaglandin D2 and
leukotriene C4). Pre-treatment of tHGA also prevented
IgE-challenged RBL-2H3 cells and peritoneal mast cells from undergoing morphological changes associated with mast cell degranulation. These findings indicate that tHGA possesses potent
anti-allergic activity via attenuation of
IgE-mediated mast cell degranulation and inhibition of
IgE-mediated passive systemic
anaphylaxis. Thus, tHGA may have the potential to be developed as a
mast cell stabilizer for the treatment of allergic diseases in the future.