Pharmacology Laboratory of Prevention and Treatment of High Incidence of Disease, Guilin Medical University, Guilin 541199, China.
Pharmacology Laboratory of Prevention and Treatment of High Incidence of Disease, Guilin Medical University, Guilin 541199, China; Guangxi Key Laboratory of Diabetic Systems Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541100, China.
Int J Biol Macromol. 2024 Nov;279(Pt 4):135565. doi: 10.1016/j.ijbiomac.2024.135565. Epub 2024 Sep 11.
Alcoholic fatty liver disease (AFLD) is characterized by excessive lipid accumulation in the liver. This study aimed to investigate the protective effects and mechanisms of Polygala fallax Hemsl polysaccharides (PFPs) on AFLD. PFPs were purified and structurally characterized. An AFLD model was established in mice using alcohol and a high-fat diet. A significant reduction in hepatic steatosis was observed following PFPs treatment, evidenced by decreased fat deposition in liver tissues. Additionally, PFPs reduced various liver injury markers, increased levels of antioxidant enzymes, and improved significantly liver function. RNA sequencing revealed that PFPs improved lipid and CYP450 metabolic pathway abnormalities in AFLD mice. Furthermore, PFPs activated the AMPK pathway, reducing lipid accumulation and enhancing lipid metabolism. A HepG2 cell model treated with ethanol and oleic acid showed significant biochemical improvements with PFPs pretreatment, including reduced lipid accumulation and lower reactive oxygen species (ROS) levels. To further elucidate the AMPK and PFPs correlation in AFLD, an AMPK inhibitor (compound C) was used. In vitro and in vivo qRT-PCR and Western blot results confirmed that PFPs protected against AFLD by activating AMPK phosphorylation, regulating lipid synthesis, and inhibiting lipid accumulation. PFPs also modulated CYP2E1 and oxidative stress-related gene expression, affecting liver metabolism.
酒精性脂肪肝疾病（AFLD）的特征是肝脏内脂质过度堆积。本研究旨在探究黄花倒水莲多糖（PFPs）对 AFLD 的保护作用及其机制。PFPs 经过分离和结构鉴定。采用酒精和高脂肪饮食构建 AFLD 小鼠模型，PFPs 处理后肝脂肪变性明显减轻，肝组织中脂肪沉积减少。此外，PFPs 降低了各种肝损伤标志物，增加了抗氧化酶水平，显著改善了肝功能。RNA 测序结果显示，PFPs 改善了 AFLD 小鼠的脂质和 CYP450 代谢途径异常。此外，PFPs 通过激活 AMPK 通路，减少脂质堆积并增强脂质代谢，发挥作用。PFPs 预处理乙醇和油酸处理的 HepG2 细胞模型，脂类堆积减少，活性氧（ROS）水平降低，细胞生化功能显著改善。为进一步阐明 AFLD 中 AMPK 与 PFPs 的相关性，使用了 AMPK 抑制剂（compound C）。体外和体内 qRT-PCR 和 Western blot 结果证实，PFPs 通过激活 AMPK 磷酸化、调节脂质合成和抑制脂质积累来防止 AFLD。PFPs 还调节 CYP2E1 和氧化应激相关基因的表达，影响肝脏代谢。
