Selenium (Se)-enriched green tea (Se-Te) has been recognized as a possible source of Se supplements, while the effect of Se enrichment on function of polyphenols in green tea is still unclear. In this study, a pseudo-targeted metabolomics strategy was carried out to reveal the regulatory mechanism of polyphenols extracted from Se-Te and regular green tea (Re-Te) on inflammatory response at cellular level. A novel analysis strategy using UHPLC/ESI Q-Orbitrap combined with MS-IOP was applied to profile the dynamic changes of metabolites in LPS-stimulated RAW264.7 macrophages during polyphenols incubation. A total of 128 characteristic variables (VIP > 1, p < 0.05) were screened in Se-Te group and the results of bioinformatics analysis and quantitative research indicated that in addition to the 6 conventional immune protective pathways involved in tea polyphenols, Se-enriched polyphenols were also participated in 3 unique antioxidant enzyme activation pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and pantothenate and CoA biosynthesis. The result of weight calculation based on topological analysis indicated that the promoting synthesis of antioxidant enzymes was the main mechanism of Se-Te polyphenols to inhibit inflammation. However, compared with Re-Te group, the intracellular B vitamin pathway in Se-Te group was disturbed, which is related to the fact that Se supplementation can promote the synthesis of selenoprotein and catalyze the reduction of thioredoxin by NADPH, thus blocking the signaling pathways of B vitamins. This study comprehensively explored the immune protective mechanism of polyphenols extracted from Se-Te and Re-Te under natural growth conditions, which could give a better understanding of the potential nutritional value of Se-Te as a widely used Se supplement.

富硒（Se）绿茶（Se-Te）已被认为是补硒的可能来源，而富硒对绿茶中多酚功能的影响尚不清楚。本研究采用伪靶向代谢组学策略，从细胞水平上揭示从 Se-Te 和普通绿茶 (Re-Te) 中提取的多酚对炎症反应的调节机制。使用 UHPLC/ESI Q-Orbitrap 结合 MS-IOP 的新分析策略用于分析 LPS 刺激的 RAW264.7 巨噬细胞在多酚孵育期间代谢物的动态变化。共有 128 个特征变量（VIP > 1, p < 0.05)在Se-Te组中筛选，生物信息学分析和定量研究结果表明，除了茶多酚参与的6条常规免疫保护途径外，富硒多酚还参与了3条独特的抗氧化酶激活途径，包括苯丙氨酸、酪氨酸和色氨酸的生物合成，苯丙氨酸的代谢和泛酸和辅酶A的生物合成。基于拓扑分析的权重计算结果表明，促进抗氧化酶的合成是Se-Te多酚抑制炎症的主要机制。然而，与 Re-Te 组相比，Se-Te 组的细胞内 B 族维生素通路受到干扰，这与补硒可以促进硒蛋白的合成，催化NADPH还原硫氧还蛋白，从而阻断B族维生素的信号通路有关。本研究全面探讨了从Se-Te和Re-Te中提取的多酚在自然生长条件下的免疫保护机制，可以更好地了解Se-Te作为广泛使用的硒补充剂的潜在营养价值。