posted on 2020-03-05, 18:19authored byChongyang Wang, Liangchang Li, Jingzhi Jiang, Li Li, Junfeng Li, Chang Xu, Shan Jin, Lianhua Zhu, Guanghai Yan
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.