Transdisciplinary Major in Learning Health Systems, Department of Integrated Biomedical and Life Science, Graduate School, Korea University, Seoul, 02841, Republic of Korea.
Major in Food & Nutrition, Korea National University of Transportation, Chungbuk 27909, Republic of Korea.
Int J Biol Macromol. 2024 Oct;277(Pt 3):134240. doi: 10.1016/j.ijbiomac.2024.134240. Epub 2024 Jul 31.
This study aimed to investigate the structural characteristics and intracellular mechanisms of polysaccharides (MP-PE-I) purified from a crabapple (Malus prunifolia) enzymatic hydrolysate (MP-PE). Activity-guided fractionation revealed that MP-PE-I was the active moiety and significantly reduced the production and gene expression of pro-inflammatory factors in interleukin (IL)-1β-treated intestinal epithelial cells (Caco-2). Moreover, MP-PE-I downregulated the phosphorylation and nuclear localization of proteins involved in the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways, as evidenced by immunoblotting and immunofluorescence analysis. In antagonistic studies with specific inhibitors of the MAPK and NF-κB pathways, IL-6 inhibition was significantly regulated by p38; IL-8 by IκBα, JNK, and p38; and monocyte chemoattractant protein-1 (MCP-1) by JNK, p38, and ERK. Additionally, MP-PE-I significantly decreased the mRNA and protein expression of IL-1 receptor type 1. Chemical and structural characteristic analyses showed that MP-PE-I is a polysaccharide rich in rhamnogalacturonan (RG)-I and plays a crucial role in intestinal immunomodulation. To our knowledge, this is the first study to demonstrate the intestinal immunomodulatory activity, intracellular mechanisms, and structural characteristics of RG-I-rich polysaccharides isolated from crabapples.
本研究旨在探究从苹果属植物(Malus prunifolia)酶解产物(MP-PE)中分离得到的多糖(MP-PE-I)的结构特征和细胞内机制。活性导向分离表明,MP-PE-I 是具有活性的部分,可显著降低白细胞介素(IL)-1β处理的肠上皮细胞(Caco-2)中促炎因子的产生和基因表达。此外,MP-PE-I 通过免疫印迹和免疫荧光分析,下调丝裂原活化蛋白激酶(MAPK)和核因子-κB(NF-κB)通路相关蛋白的磷酸化和核定位。用 MAPK 和 NF-κB 通路的特异性抑制剂进行拮抗研究表明,IL-6 的抑制作用主要由 p38 调节;IL-8 由 IκBα、JNK 和 p38 调节;MCP-1 由 JNK、p38 和 ERK 调节。此外,MP-PE-I 还显著降低了 IL-1 受体 1 的 mRNA 和蛋白表达。化学和结构特征分析表明,MP-PE-I 是一种富含鼠李半乳糖醛酸聚糖(RG-I)的多糖,在肠道免疫调节中发挥重要作用。据我们所知,这是首次报道从苹果属植物中分离得到的 RG-I 丰富的多糖具有肠道免疫调节活性、细胞内机制和结构特征。