Screening of Phytotoxins in Raw Honey and the Honey Sugar Matrix’s Modulatory Effects on Their Toxicity

Honey, as a natural and nutritious sweetener, is one of the most widely consumed foods worldwide. However, the presence of phytotoxins in honey and the influence of honey's intrinsic sugar matrix on the toxicity of these phytotoxins remain insufficiently explored. An optimized liquid chromatography-quadrupole trap tandem mass spectrometry method was developed to quantify 17 toxic alkaloids in 150 raw honey samples. Camptothecin was identified for the first time in the tested samples and was the most prevalent contaminant (36% detection, max 3.09 μg/kg), which induced cardiac hypertrophy and impaired cardiac function in zebrafish assays. The honey sugar matrix further potentiated these adverse cardiac effects through exacerbating oxidative stress and upregulating pro-inflammatory and pro-apoptotic gene expression, while natural honey partially mitigated such damage by upregulating the key antioxidant gene <i>nrf2</i>, thereby downregulating <i>il-1β</i> and regulating the <i>bcl2</i>/<i>bax</i> expression ratio. This study offers novel insights into honey phytotoxins' matrix-modulated toxicity, laying a scientific foundation for optimizing safety protocols and matrix-specific risk standards.