Bai Hong-Xin, Gao Yu-Xuan, Wang Shuyao, Ma Guang-Yuan, Zhao Wenjing, Li Xiao-Qiang, Wang Yu-Fan, Nong Qiu-Na, Wang Yu-Bo, Tan Jin, Duan Qimei, Cao Wei
Shaanxi Key Laboratory of Natural Products & Chemical Biology, School of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, China.
Department of Chinese Materia Medica and Natural Medicines, School of Pharmacy, Air Force Medical University, Xi'an 710032, China; Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Air Force Medical University, Xi'an 710032, China.
Carbohydr Polym. 2025 Mar 15;352:123153. doi: 10.1016/j.carbpol.2024.123153. Epub 2024 Dec 15.
Alcoholic fatty liver disease (AFLD) is characterized by the accumulation of hepatic lipid and has no effective treatment yet. Fructus Corni is a traditional Chinese medicinal herb, and its extractions have demonstrated hepatoprotective properties. We hypothesize that the polysaccharides in Fructus Corni might have therapeutic effects on AFLD. In this study, we isolated a novel homogeneous polysaccharide, APFC-2 (Mw= 63.0 kDa), from the Fructus Corni, and its structure was elucidated by monosaccharide composition, methylation analysis, partial acid hydrolysis, and NMR spectra. APFC-2 is a pectic polysaccharide characterized by a backbone of T-β-Galp-(1 → 6)-β-Galp-(1 → 3,6)-β-Galp-(1 → [4)-α-GalpA-OMe-(1 → 4)-α-GalpA-(1→] → [2,4)-α-Rhap-(1 → 4)-α-GalpA-(1→], with branches comprising T-Araf-(1→, →3)-α-Araf-(1→, →3,5)-α-Araf-(1→, and →5)-α-Araf-(1→. In vivo experiments indicated that APFC-2 could significantly reduce hepatic steatosis, fasting triglyceride, and cholesterol levels in AFLD mice. Cell proliferation and Oil Red O staining results showed that APFC-2 concentration-dependently increased cell viability and significantly improved lipid metabolism in vitro. Mechanistically, APFC-2 markedly inhibited the formation of lipid both in vitro and in vivo through activating liver kinase B1 (LKB1) and then regulating adenosine 5'-monophosphate-activated protein kinase (AMPK)-SREBP-1 and AMPK-PPAR-α pathways. This research provides a theoretical basis for the potential application of Fructus Corni pectic polysaccharide as a specific activator of LKB1 for treating AFLD.
酒精性脂肪肝病（AFLD）的特征是肝脏脂质蓄积，目前尚无有效治疗方法。山茱萸是一种传统中草药，其提取物已显示出肝脏保护特性。我们推测山茱萸中的多糖可能对AFLD具有治疗作用。在本研究中，我们从山茱萸中分离出一种新型的均一多糖APFC-2（Mw = 63.0 kDa），并通过单糖组成、甲基化分析、部分酸水解和核磁共振光谱对其结构进行了阐明。APFC-2是一种果胶多糖，其主链为T-β-半乳糖-(1→6)-β-半乳糖-(1→3,6)-β-半乳糖-(1→[4)-α-半乳糖醛酸甲酯-(1→4)-α-半乳糖醛酸-(1→]→[2,4)-α-鼠李糖-(1→4)-α-半乳糖醛酸-(1→]，分支包括T-阿拉伯糖-(1→、→3)-α-阿拉伯糖-(1→、→3,5)-α-阿拉伯糖-(1→和→5)-α-阿拉伯糖-(1→。体内实验表明，APFC-2可显著降低AFLD小鼠的肝脏脂肪变性、空腹甘油三酯和胆固醇水平。细胞增殖和油红O染色结果表明，APFC-2在体外呈浓度依赖性增加细胞活力并显著改善脂质代谢。机制上，APFC-2通过激活肝脏激酶B1（LKB1），进而调节5'-单磷酸腺苷激活蛋白激酶（AMPK）-固醇调节元件结合蛋白-1（SREBP-1）和AMPK-过氧化物酶体增殖物激活受体-α（PPAR-α）途径，在体外和体内均显著抑制脂质形成。本研究为山茱萸果胶多糖作为治疗AFLD的LKB1特异性激活剂的潜在应用提供了理论依据。
