Pterostilbene Inhibits FcεRI Signaling through Activation of the LKB1/AMPK Pathway in Allergic Response

In this study, the role and mechanism of pterostilbene (Pts) in mast cell degranulation in vitro and in vivo were investigated. The results showed that Pts inhibited mast cell-mediated local passive allergic reactions in mice. In addition, treatment with Pts reduced both histamine release and calcium influx in rat peritoneal mast cells and RBL-2H3 cells and reduced IgE-mediated mast cell activation. Furthermore, the mechanism underlying Pts inhibition of mast cell signaling was probed via studying the effects of Pts on liver kinase B1 (LKB1), including the use of the LKB1 activator metformin and siRNA knockdown of LKB1. The data showed that Pts reduced the release of inflammatory mediators such as tumor necrosis factor-α, interleukin-6, leukotriene C4, and prostaglandin D2 in mast cells by activating the LKB1/adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Furthermore, Pts inhibited phosphorylation of FcεRI and FcεRI-mediated degranulation in RBL-2H3 cells. These effects were attenuated after LKB1 knockdown. Taken together, Pts could inhibit FcεRI signaling through activation of the LKB1/AMPK signaling pathway in IgE-mediated mast cell activation. Thus, Pts might be an effective therapeutic agent for mast cell-mediated allergic diseases.