Phenolics from Ilex rotunda Possess Antioxidative Effects and Block Activation of MAPK and NF-κB Signaling by Inhibiting IL-2 Production in CD3/CD28 Activated Jurkat T Cells.

Ilex rotunda, an evergreen tree in the holly family, is a traditional medicine with a high phenolic content and various pharmacological effects. This study aimed to investigate phenolic constituents from enriched fractions guided by a total phenolic assay along with a feature-based molecular network. Nine compounds were isolated and identified using multiple chromatography and spectroscopic techniques. These isolates exhibited significantly high antioxidative effects in both free radical scavenging and ROS assays. They also remarkedly alternated interleukin (IL)-2 production in CD3/CD28-stimulated Jurkat T cells. The Western blotting assay suggested that these active compounds might decrease IL-2 production by blocking the activation of NF-κB and MAPK signaling pathways by downregulating the phosphorylation of p38 and p65 proteins as well as ERK and JNK kinases. Molecular docking data confirmed the above-mentioned biological properties of those active compounds by evaluating their binding affinities for target proteins. Our findings offer guidance for assessing the potential of phenolic chemicals from I. rotunda as pharmacological products to improve oxidative stress and enhance immune response in more in-depth studies.