Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing 100083, China.
National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Nutrients. 2019 Apr 27;11(5):963. doi: 10.3390/nu11050963.
Natural polysaccharides, particularly galactomannans, are potential candidates for treatment of alcoholic liver diseases (ALD). However, applications are restricted due to the physicochemical properties associated with the high molecular weight. In this work, guar gum galactomannans were partially hydrolyzed by β-mannanase, and the molecular mechanisms of hepatoprotective effects were elucidated both in vitro and in vivo. Release of lactate dehydrogenase and cytochrome C were attenuated by partially hydrolyzed guar gum (PHGG) in HepG2 cells, due to protected cell and mitochondrial membrane integrity. PHGG co-administration decreased serum amino transaminases and cholinesterase levels of acute alcohol intoxicated mice, while hepatic pathologic morphology was depleted. Activity of superoxide dismutase, catalase, and glutathione peroxidase was recovered to 198.2, 34.5, 236.0 U/mg protein, respectively, while malondialdehyde level was decreased by 76.3% (PHGG, 1000 mg/kg∙day). Co-administration of PHGG induced a 4.4-fold increment of p-AMPK expression, and lipid metabolism was mediated. PHGG alleviated toll-like-receptor-4-mediated inflammation via the signaling cascade of MyD88 and IκBα, decreasing cytokine production. Moreover, mediated expression of Bcl-2 and Bax was responsible for inhibited acute alcohol-induced apoptosis with suppressed cleavage of caspase 3 and PARP. Findings gained suggest that PHGG can be used as functional food supplement for the treatment of acute alcohol-induced liver injury.
天然多糖，特别是半乳甘露聚糖，是治疗酒精性肝病（ALD）的潜在候选药物。然而，由于其高分子量相关的理化性质，其应用受到限制。在这项工作中，β-甘露聚糖酶对半乳糖甘露聚糖进行了部分水解，从体外和体内阐明了其肝保护作用的分子机制。部分水解瓜尔胶（PHGG）可减轻 HepG2 细胞中乳酸脱氢酶和细胞色素 C 的释放，这是由于细胞和线粒体膜完整性得到了保护。PHGG 与急性酒精中毒小鼠共给药可降低血清氨基转移酶和胆碱酯酶水平，同时减轻肝组织病理形态学损伤。超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性分别恢复到 198.2、34.5 和 236.0 U/mg 蛋白，而丙二醛水平降低了 76.3%（PHGG，1000mg/kg·天）。PHGG 共给药诱导 p-AMPK 表达增加 4.4 倍，并介导脂质代谢。PHGG 通过 MyD88 和 IκBα 的信号级联反应减轻 Toll 样受体 4 介导的炎症，减少细胞因子的产生。此外，Bcl-2 和 Bax 的介导表达负责抑制急性酒精诱导的凋亡，同时抑制 caspase 3 和 PARP 的切割。研究结果表明，PHGG 可用作治疗急性酒精性肝损伤的功能性食品补充剂。
