Accumulating evidence has shown that high-fat diet (HFD) can lead to intestinal epithelial barrier dysfunction. We previously found that 6-shogaol was able to attenuate palmitic acid (PA)-induced intestinal barrier damages in human intestinal epithelial Caco-2 cells through regulation of tight junctions (TJs). However, the in vivo protective effects and action mechanism of 6-shogaol against HFD-induced intestinal barrier dysfunction remains unexplored. In this study, HFD-fed C57BL/6J mice were used as the intestinal barrier dysfunction model to investigate the protective effects of 6-shogaol. The results showed that the 6-shogaol significantly (P < 0.05) suppressed HFD-stimulated increase of serum fluorescein isothiocyanate (FITC)-dextran level and proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α)) in the ileum, whilst significantly (P < 0.05) increased the expression of TJ-associated proteins (e.g., Zona occludens 1, occludin, and claudin-1). Furthermore, miR-sequencing and qRT-PCR analysis revealed that miR-215-3p_R+1 was one of the highest expressed miRNAs in the ileum in response to the 6-shogaol treatment. MiR-215-3p_R+1 overexpression significantly (P < 0.01) downregulated occludin expression in PA-treated Caco-2 cells compared with the mimics NC+PA+6-shogaol group, partially compromising the protective effects 6-shogoal against intestinal epithelial barrier dysfunction. Taken together, these findings provide the evidence for the first time that 6-shogaol has the potential to treat HFD-induced TJs impairment via the miR-215-3p_R+1/occludin axis.

In this study, the dissipation, terminal residues and dietary risk of the cyazofamid residue in three globally consumed minor crops, turnip (Brassica rapa L.), onion (Allium cepa L.) and romaine lettuce (Lactuca sativa L.) were assessed by supervised field trials at 6 locations of China in 2020. A reliable QuEChERS-LC-MS/MS method was developed for simultaneous analysis of cyazofamid and its primary metabolite, 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM). The average recoveries of cyazofamid and CCIM in turnip, onion and romaine lettuce were 79%–97% and 77%–99%, respectively. The half-lives of cyazofamid in these crops were 5.7–6.5, 5.3–8.7 and 5.8–6.5 days in turnip, onion and romaine lettuce, respectively, with the final cyazofamid residues at harvest all lower than limit of quantitation (LOQ, 0.01 mg/kg). The turnip roots, onion bulbs and romaine lettuce leaves grown in China under Good Agricultural Practices conditions and harvested 10, 14 and 5 days, respectively, after the cyazofamid SC (100 g/L) application, would be reasonably safe for consumption by the general population. The maximum residue limit (MRL) values of cyazofamid could be tentatively set as 10 mg/kg for turnip leaves, 0.3 mg/kg for turnip roots, 0.05 mg/kg for onion bulbs, and 10 mg/kg for romaine lettuce leaves.