University of València Faculty of Pharmacy, Laboratory of Food Chemistry and Toxicology, Burjassot, Spain.
University of Ferrara, Department of Chemistry and Pharmaceutical Sciences, Ferrara, Italy.
Arh Hig Rada Toksikol. 2021 Sep 28;72(3):173-181. doi: 10.2478/aiht-2021-72-3541.
Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract (from the pulp) against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach. The cells were added with mycotoxins at a concentration of 100 nmol/L per mycotoxin and pumpkin carotenoid extract at 500 nmol/L. For control we used only vehicle solvent (cell control) or vehicle solvent with pumpkin extract (extract control). After two hours of exposure, samples were analysed with HPLC-ESI-QTOF-MS. Metabolites were identified against the Metlin database. The proinflammatory arachidonic acid metabolite eoxin (14,15-LTE4) showed lower abundance in ZEA and BEA+OTA+ZEA-treated cultures that also received the pumpkin extract than in cultures that were not treated with the extract. Another marker of inflammation, prostaglandin D2-glycerol ester, was only found in cultures treated with OTA+ZEA and BEA+OTA+ZEA but not in the ones that were also treated with the pumpkin extract. Furthermore, the concentration of the pumpkin extract metabolite dihydromorelloflavone significantly decreased in the presence of mycotoxins. In conclusion, the pumpkin extract showed protective activity against cellular inflammation triggered by mycotoxins thanks to the properties pertinent to flavonoids contained in the pulp.
一些霉菌毒素，如伏马菌素（BEA）、赭曲霉毒素 A（OTA）和玉米赤霉烯酮（ZEA）可以穿过血脑屏障，这就是为什么我们使用非靶向代谢组学方法，在共培养的 ECV304 和 C6 细胞的血脑屏障模型上，测试了南瓜类胡萝卜素提取物（来自果肉）对这些霉菌毒素及其组合（OTA+ZEA 和 OTA+ZEA+BEA）的抗炎作用。将霉菌毒素以每种霉菌毒素 100nmol/L 的浓度和南瓜类胡萝卜素提取物 500nmol/L 的浓度添加到细胞中。作为对照，我们仅使用载体溶剂（细胞对照）或含有南瓜提取物的载体溶剂（提取物对照）。暴露两小时后，用 HPLC-ESI-QTOF-MS 分析样品。针对 Metlin 数据库对代谢物进行鉴定。在接受南瓜提取物处理的 ZEA 和 BEA+OTA+ZEA 处理培养物中，促炎花生四烯酸代谢物 eoxin（14,15-LTE4）的丰度低于未用提取物处理的培养物。另一种炎症标志物前列腺素 D2-甘油酯，仅在 OTA+ZEA 和 BEA+OTA+ZEA 处理的培养物中发现，而在同时用南瓜提取物处理的培养物中未发现。此外，在存在霉菌毒素的情况下，南瓜提取物代谢物二氢杨梅素的浓度显著降低。总之，南瓜提取物由于果肉中含有的类黄酮的特性，对霉菌毒素引起的细胞炎症表现出保护活性。
