Carbohydrate-Based Drug Research Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
Carbohydrate-Based Drug Research Center, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; Zhongshan Institute for Drug Discovery, Zhongshan Tsuihang New District, Zhongshan 528400, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Carbohydr Polym. 2024 Aug 1;337:122139. doi: 10.1016/j.carbpol.2024.122139. Epub 2024 Apr 8.
A novel RG-I pectin-like polysaccharide, YJ3A1, was purified from the flowers of Rosa chinensis and its structure and hepatoprotective effect in vivo and in vitro were investigated. The backbone of this polysaccharide is mainly composed of 1, 4-galactan, 1, 4-linked α-GalpA and 1, 2-linked α-Rhap disaccharide repeating unit attached by 1, 6-linked β-Galp or 1, 5-linked α-Araf on C-4 of the Rhap. Interestingly, oral administration of YJ3A1 significantly ameliorates NASH-associated inflammation, oxidative stress and fibrosis and does not affect the liver morphology of normal mice at a dose of 50 mg/kg. The mechanism study suggests that the biological activity may associate to inactivating of high-mobility group box 1 protein (HMGB1)/TLR4/NF-κB and Akt signaling pathways by restraining the expression and release of HMGB1, thereby impeding the effect of NASH. The current findings outline a novel leading polysaccharide for new drug candidate development against NASH.
从月季花中纯化得到一种新型 RG-I 型果胶样多糖 YJ3A1,研究了其结构及其体内和体外的保肝作用。该多糖的骨架主要由 1,4-半乳糖、1,4-连接的α-GalpA 和 1,2-连接的α-Rhap 二糖重复单元组成,在 Rhap 的 C-4 上通过 1,6-连接的β-Galp 或 1,5-连接的α-Araf 连接。有趣的是,50mg/kg 剂量的 YJ3A1 可显著改善 NASH 相关炎症、氧化应激和纤维化,而对正常小鼠的肝脏形态没有影响。机制研究表明,生物活性可能与通过抑制 HMGB1 的表达和释放来抑制高迁移率族蛋白 1(HMGB1)/TLR4/NF-κB 和 Akt 信号通路的活性有关,从而阻碍 NASH 的发生。目前的研究结果为开发治疗 NASH 的新型药物候选物提供了一种新型先导多糖。