Xie Yujun, Tao Mingxing, Yan Xiaodong, Fan Xinxin, Bayoude Alamusi, Lu Yu, Zhao Shuangli, Yu Boyang, Li Renshi
Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
Jiangsu Provincial Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China; Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 8128582, Japan.
Int J Biol Macromol. 2025 May;310(Pt 2):143145. doi: 10.1016/j.ijbiomac.2025.143145. Epub 2025 Apr 13.
Dioscoreae Rhizoma polysaccharides exhibit gastrointestinal protective properties, yet their efficacy against acute alcoholic liver injury (AALI) remains unexplored. This study identifies a novel acidic heteropolysaccharide (CP-2, Mw = 8.4 × 10 kDa) with galactose/galacturonic acid dominance and delineates its multimodal hepatoprotective mechanisms. In AALI mice, CP-2 attenuated liver injury by enhancing ADH and ALDH activities while restoring redox balance via SOD/CAT activation and MDA reduction, and suppressed inflammation by inhibiting IL-1β, IL-6, and TNF-α levels. Gut-liver axis modulation was achieved through intestinal barrier reinforcement (ZO-1, Occludin, Claudin-1) and microbiota rebalancing. CP-2 could reduce gram-negative bacteria ([Ruminococcus]_ torques_ group and Escherichia- Shigella) and Proteobacteria abundance while enriching Bacteroides and Akkermansia abundance, which collectively suppressed serum LPS level. In addition, CP-2 could activate the AMPK/PPAR signaling pathway to reduce the production of fatty acids and promote their degradation in AALI. CP-2 can improve AALI by adjusting the composition of gut microbiota, repairing intestinal barrier function, decreasing systemic inflammation and oxidative reactions, and regulating the AMPK/PPAR pathway. Our findings unveil CP-2 as a prebiotic candidate for AALI intervention and may advance functional food development for alcohol-related hepatopathies.
山药多糖具有胃肠道保护特性，但其对急性酒精性肝损伤（AALI）的疗效仍未得到探索。本研究鉴定出一种以半乳糖/半乳糖醛酸为主的新型酸性杂多糖（CP-2，Mw = 8.4 × 10 kDa），并阐述了其多模式肝脏保护机制。在AALI小鼠中，CP-2通过增强ADH和ALDH活性减轻肝损伤，同时通过激活SOD/CAT和降低MDA来恢复氧化还原平衡，并通过抑制IL-1β、IL-6和TNF-α水平来抑制炎症。通过加强肠道屏障（ZO-1、闭合蛋白、Claudin-1）和微生物群再平衡实现肠-肝轴调节。CP-2可以降低革兰氏阴性菌（[瘤胃球菌]_扭矩_组和大肠杆菌-志贺氏菌属）和变形菌门丰度，同时增加拟杆菌属和阿克曼氏菌属丰度，共同抑制血清LPS水平。此外，CP-2可以激活AMPK/PPAR信号通路，以减少脂肪酸的产生并促进其在AALI中的降解。CP-2可以通过调节肠道微生物群组成、修复肠道屏障功能、减少全身炎症和氧化反应以及调节AMPK/PPAR途径来改善AALI。我们的研究结果揭示CP-2作为AALI干预的益生元候选物，并可能推动酒精相关肝病的功能性食品开发。
