Liu Yanglong, Sun Jiawei, Yan Qihao, Wen Bingjian, Bai Yan, Che Qishi, Cao Hua, Guo Jiao, Su Zhengquan
Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Mar Drugs. 2025 Mar 19;23(3):134. doi: 10.3390/md23030134.
Alcoholic liver disease (ALD) is a liver disorder resulting from excessive alcohol intake, and currently, there are no therapeutics approved by the FDA for its treatment. This study investigates the protective effects and underlying pharmacological mechanisms of two chitosan oligosaccharides, COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da), in mitigating alcohol-induced liver disease (ALD). In animal models, we evaluated the changes in ALD following treatment with COST and COSM. Histopathological analysis revealed that both COST and COSM interventions mitigated hepatic steatosis and inflammatory infiltration. Additionally, these compounds reduced various markers of liver injury, enhanced antioxidant enzyme levels, and significantly improved liver function. Western blot analysis demonstrated that COSM markedly decreased the expression of the hepatic metabolic enzyme CYP2E1, activated the Keap-1/Nrf-2/HO-1 pathway, and restrained the NF-κB and MAPK pathways. In an in vitro model of alcohol-induced hepatocyte L02 injury, both COST and COSM exhibited protective effects on hepatocytes, corroborating the findings from the animal studies. Collectively, in vivo and in vitro experiments confirmed that COST and COSM can reduce oxidative damage, enhance antioxidant capacity, and ameliorate steatosis and inflammatory damage in the liver, thereby significantly attenuating alcohol-induced injury. Notably, COSM exhibited slightly superior efficacy compared to COST.
酒精性肝病（ALD）是一种因过量饮酒导致的肝脏疾病，目前美国食品药品监督管理局（FDA）尚未批准任何用于治疗该病的药物。本研究调查了两种壳寡糖，即COST（分子量≤1000道尔顿）和COSM（分子量≤3000道尔顿）在减轻酒精性肝病（ALD）方面的保护作用及潜在药理机制。在动物模型中，我们评估了用COST和COSM治疗后ALD的变化。组织病理学分析显示，COST和COSM干预均减轻了肝脂肪变性和炎症浸润。此外，这些化合物降低了各种肝损伤标志物，提高了抗氧化酶水平，并显著改善了肝功能。蛋白质免疫印迹分析表明，COSM显著降低了肝脏代谢酶CYP2E1的表达，激活了Keap-1/Nrf-2/HO-1通路，并抑制了NF-κB和MAPK通路。在酒精诱导的肝细胞L02损伤的体外模型中，COST和COSM均对肝细胞表现出保护作用，这与动物研究结果一致。总体而言，体内和体外实验证实，COST和COSM可以减少氧化损伤，增强抗氧化能力，改善肝脏脂肪变性和炎症损伤，从而显著减轻酒精诱导的损伤。值得注意的是，COSM的疗效略优于COST。
