Lee Jisun, Choi Ji Won, Sohng Jae Kyung, Pandey Ramesh Prasad, Park Yong Il
Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, 420-743, Republic of Korea.
Institute of Biomolecule Reconstruction, Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Chungnam, 336-708, Republic of Korea.
Int Immunopharmacol. 2016 Feb;31:88-97. doi: 10.1016/j.intimp.2015.12.008. Epub 2015 Dec 17.
Quercetin is a natural plant flavonoid that has been reported to possess a wide range of beneficial health effects, including anti-cancer and anti-inflammatory activities. Glycosylation of natural flavonoids with various sugar moieties can affect their physical, chemical, and biological properties. In this study, quercetin 3-O-xyloside (Quer-xyl) was enzymatically synthesized, and the immunomodulatory activities of quercetin and Quer-xyl were evaluated and compared. The results showed that Quer-xyl more effectively induced the secretion of TNF-α and IL-6 than quercetin by 2.5 and 1.5-fold, respectively. Quer-xyl dose-dependently induced the inducible nitric oxide synthase (iNOS) expression and increased the production of nitric oxide (NO) 1.3-fold more than quercetin. Quer-xyl also increased the phosphorylation of ASK1 and MAPKs (JNK and p38). Treatment with NQDI-1 (an inhibitor of ASK1) significantly attenuated the Quer-xyl-induced up-regulation of TNF-α secretion. The activation and subsequent nuclear translocation of NF-κB were substantially enhanced upon treatment with Quer-xyl (2.5-20 μM), while NQDI-1 treatment blocked the nuclear translocation of NF-κB. These results demonstrated that Quer-xyl can enhance the early innate immunity more effectively than quercetin by activating macrophages to secrete TNF-α and IL-6 through up-regulation of the redox-dependent ASK1/MAPK/NF-κB signaling pathway, suggesting for the first time that Quer-xyl may represent a new immunostimulator.
槲皮素是一种天然植物黄酮类化合物，据报道具有广泛的有益健康作用，包括抗癌和抗炎活性。天然黄酮类化合物与各种糖基的糖基化会影响其物理、化学和生物学性质。在本研究中，酶法合成了槲皮素3 - O -木糖苷（Quer - xyl），并评估和比较了槲皮素和Quer - xyl的免疫调节活性。结果表明，Quer - xyl诱导TNF -α和IL - 6分泌的效果分别比槲皮素有效2.5倍和1.5倍。Quer - xyl剂量依赖性地诱导诱导型一氧化氮合酶（iNOS）表达，并且使一氧化氮（NO）的产生比槲皮素增加1.3倍。Quer - xyl还增加了ASK1和丝裂原活化蛋白激酶（JNK和p38）的磷酸化。用NQDI - 1（ASK1抑制剂）处理显著减弱了Quer - xyl诱导的TNF -α分泌上调。用Quer - xyl（2.5 - 20μM）处理后，NF -κB的活化及其随后的核转位显著增强，而NQDI - 1处理则阻断了NF -κB的核转位。这些结果表明，Quer - xyl通过上调氧化还原依赖性ASK1 / MAPK / NF -κB信号通路激活巨噬细胞分泌TNF -α和IL - 6，比槲皮素更有效地增强早期固有免疫，首次表明Quer - xyl可能代表一种新的免疫刺激剂。
