Wang Yu, Lang Rui, Li Lilang, Wen Yonglan, Gao Ming, Zhang Jie, Yang Juan, Li Qiji, Wang Li, Yang Xiaosheng, Wang Xiaolong, Xie Chunzhi
State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Guizhou Medical University, Guiyang, China.
Natural Products Research Center of Guizhou Province, Guiyang, China.
Front Nutr. 2025 Aug 12;12:1617931. doi: 10.3389/fnut.2025.1617931. eCollection 2025.
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the excessive accumulation of lipids as a pathological feature. Previous studies have demonstrated that Rosa roxburghii Tratt. fruit vinegar (RFV) played an important role in intervening in obesity and related complications by regulating the intestinal microbiota in high-fat diet mice.
This study investigated the mechanisms by which RFV improves NAFLD from multiple perspectives. Potential targets were predicted by network pharmacology and molecular docking analyses. Intestinal microbial communities were detected and analyzed using 16S rRNA gene sequencing technology. Liver metabolites were detected and analyzed using ultra high performance liquid chromatography quadrupole-exactive high field-X mass spectrometer (UHPLC-Q-Exactive HF-X) and Progenesis QI software. Hepatic protein expression levels were detected and quantified using Western blotting analysis and gray-value analysis, respectively.
The results indicated that, RFV could improve the diversity of intestinal microbiota in NAFLD mice, reduce the ratio of Firmicutes to Bacteroidetes (F/B), and reverse the relative abundance of differential bacteria genera related to lipid accumulation and energy metabolism. The intestinal microbiota was correlated with the levels of lipid metabolism and oxidative stress in the serum and liver of mice with NAFLD. The primary bacteria genera involved were . A total of 441 liver metabolites were identified in NAFLD mice and participating in 21 metabolic pathways. Glycerophospholipid metabolism may be an important pathway regulating NAFLD by RFV. Phosphatidylcholines (PC) and lysophosphatidylcholinergic (LPC) metabolites were significantly regulated by RFV and had significant correlation with differential microbiota. RFV may improve NAFLD by regulating lipid synthesis in the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway. Western blotting analysis showed that, RFV could activate the AMPK phosphorylation, and reduce the expression of fatty acid synthase (FASN) and sterol regulatory element-binding protein 1 (SREBP-1c), resulting in the inhibition of fatty acids de novo synthesis and lipid accumulation.
As a functional food, RFV has been proven to be effective in improving NAFLD. The underlying mechanisms involve the modulation of the intestinal microbiota and metabolites balance, and regulation on lipid disorders through AMPK signaling pathway.
非酒精性脂肪性肝病（NAFLD）是一种以脂质过度蓄积为病理特征的慢性肝病。既往研究表明，刺梨果醋（RFV）通过调节高脂饮食小鼠的肠道微生物群，在干预肥胖及相关并发症方面发挥重要作用。
本研究从多个角度探讨RFV改善NAFLD的机制。通过网络药理学和分子对接分析预测潜在靶点。采用16S rRNA基因测序技术检测和分析肠道微生物群落。使用超高效液相色谱四极杆-高分辨质谱仪（UHPLC-Q-Exactive HF-X）和Progenesis QI软件检测和分析肝脏代谢物。分别采用蛋白质印迹分析和灰度值分析检测和定量肝脏蛋白表达水平。
结果表明，RFV可改善NAFLD小鼠肠道微生物群的多样性，降低厚壁菌门与拟杆菌门的比例（F/B），并逆转与脂质蓄积和能量代谢相关的差异细菌属的相对丰度。肠道微生物群与NAFLD小鼠血清和肝脏中的脂质代谢水平及氧化应激相关。主要涉及的细菌属为 。在NAFLD小鼠中共鉴定出441种肝脏代谢物，参与21条代谢途径。甘油磷脂代谢可能是RFV调节NAFLD的重要途径。RFV显著调节磷脂酰胆碱（PC）和溶血磷脂酰胆碱（LPC）代谢物，且与差异微生物群具有显著相关性。RFV可能通过调节腺苷酸活化蛋白激酶（AMPK）途径中的脂质合成来改善NAFLD。蛋白质印迹分析表明，RFV可激活AMPK磷酸化，并降低脂肪酸合酶（FASN）和固醇调节元件结合蛋白1（SREBP-1c）的表达，从而抑制脂肪酸的从头合成和脂质蓄积。
作为一种功能性食品，RFV已被证明对改善NAFLD有效。其潜在机制包括调节肠道微生物群和代谢物平衡，以及通过AMPK信号通路调节脂质紊乱。
