Zingerone Targets LKB1/AMPK to Block FcεRI-Dependent Mast Cell Degranulation and Anaphylaxis

TL;DR

Zingerone, a compound in ginger, prevents allergic reactions by activating the LKB1/AMPK pathway, reducing mast cell activity and anaphylaxis.

Contribution

This study reveals Zingerone's novel anti-allergic mechanism through LKB1/AMPK activation in mast cells.

Findings

Zingerone suppresses FcεRI-mediated signaling and degranulation in mast cells via LKB1/AMPK activation.

Zingerone reduces anaphylaxis in vivo by inhibiting histamine and eicosanoid release.

Zingerone decreases pro-inflammatory cytokines and calcium influx in mast cells.

Abstract

AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and a central regulator of metabolism. Recent studies indicate that pharmacological AMPK activation can simultaneously ameliorate metabolic disorders (e.g., type II diabetes, obesity) and allergic diseases. Zingerone, a primary bioactive compound in ginger, demonstrates protective effects in vascular calcification, non-alcoholic fatty liver disease, and asthma via AMPK activation. This study aimed to evaluate the anti-allergic activity of Zingerone and elucidate its AMPK-dependent mechanisms. In vitro, Zingerone suppressed FcεRI-mediated phosphorylation of PLCγ1, Akt, ERK1/2, JNK, p38, and IKK, while reducing β-hexosaminidase release, eicosanoid (LTC4/PGD2) generation, pro-inflammatory cytokine (TNF-α/IL-6) secretion, and Ca2+ influx through LKB1/AMPK activation. In vivo, Zingerone (25–50 mg/kg, oral) attenuated passive cutaneous anaphylaxis (reduced Evans blue extravasation) and systemic anaphylaxis (inhibited histamine/LTC4/PGD2 release). These findings demonstrate that Zingerone inhibits FcεRI-dependent mast cell activation and anaphylaxis via the LKB1/AMPK pathway, highlighting its therapeutic potential for mast cell-mediated allergic diseases.

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