竹节参总皂苷通过miR-1a-3p/PLD1途径抑制磷脂酰胆碱水解并减轻肝脂肪变性。
Total saponins from Panax japonicus inhibit phosphatidylcholine hydrolysis and relieve hepatic steatosis via the miR-1a-3p/PLD1 pathway.
作者信息
Yang Ning, Yang Jingjie, Shi Yulan, Wang Shuwen, Yao Qianqian, Yuan Chengfu
机构信息
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China; College of Basic Medical Science, China Three Gorges University, Yichang 443002, China; Third-grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China.
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443002, China; College of Medicine and Health Science, China Three Gorges University, Yichang 443002, China.
出版信息
Phytomedicine. 2025 Sep;145:157050. doi: 10.1016/j.phymed.2025.157050. Epub 2025 Jul 7.
BACKGROUND
Panax japonicus (T. Nees) C.A. Mey., a member of the Araliaceae family, has been utilized for medicinal purposes by the Tujia and Hmong ethnic groups in China for over a thousand years. In traditional Chinese medicine, metabolic dysfunction-associated fatty liver disease (MAFLD) is classified as a damp-heat syndrome, and P. japonicus is believed to strengthen the spleen and the stomach, promoting fat transformation. Previous studies have shown that the total saponins from P. japonicus (TSPJ) are the primary active constituents that exert hepatoprotective, lipid-lowering, and anti-inflammatory effects in the advanced stages of MAFLD.
PURPOSE
This work examines the effects of TSPJ on early stage MAFLD (i.e., hepatic steatosis) and explores their potential as a novel therapeutic strategy to prevent disease progression.
METHODS
Animal models were created by administering a high-fat diet (HFD) to mice, and cell models were established by stimulating AML12 hepatocytes with palmitic acid (PA). The changes in lipid metabolism in the models receiving TSPJ, having miR-1a-3p knockdown, and/or having PLD1 knockdown were examined using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, immunofluorescence, etc. Non-targeted metabolomic analysis was employed to detect the effects of TSPJ on lipid species.
RESULTS
For the mouse model, TSPJ significantly reduced body weight (p < 0.001) and liver weight (p < 0.001) and improved liver function. For both the mouse and cell models, TSPJ decreased lipid accumulation (p = 0.05) and inhibited the expression of the lipogenic genes Acaca (p < 0.001; p = 0.02), Fasn (p = 0.008; p = 0.001), and Scd1 (p = 0.05; p = 0.05). According to non-targeted metabolomic analysis, phosphatidylcholine (PC) was the primary lipid species affected by TSPJ. PLD1, which is a downstream target of miR-1a-3p, was the crux in the regulation of lipid metabolism by TSPJ. The efficacy of TSPJ was lost when the models had miR-1a-3p knockdown.
CONCLUSIONS
TSPJ mitigated hepatocyte steatosis by upregulating miR-1a-3p, which inhibited PLD1 to reduce PC hydrolysis, ultimately decreasing hepatic lipid accumulation.
背景
竹节参（Panax japonicus (T. Nees) C.A. Mey.）是五加科植物，在中国土家族和苗族中作为药用植物已有一千多年的历史。在传统中医中，代谢功能障碍相关脂肪性肝病（MAFLD）被归类为湿热证，竹节参被认为具有健脾和胃、促进脂肪转化的作用。先前的研究表明，竹节参总皂苷（TSPJ）是在MAFLD晚期发挥肝脏保护、降脂和抗炎作用的主要活性成分。
目的
本研究考察TSPJ对MAFLD早期（即肝脂肪变性）的影响，并探索其作为预防疾病进展的新型治疗策略的潜力。
方法
通过给小鼠喂食高脂饮食（HFD）建立动物模型，通过用棕榈酸（PA）刺激AML12肝细胞建立细胞模型。使用定量实时聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法、免疫荧光等方法检测接受TSPJ、敲低miR-1a-3p和/或敲低PLD1的模型中脂质代谢的变化。采用非靶向代谢组学分析检测TSPJ对脂质种类的影响。
结果
对于小鼠模型，TSPJ显著降低体重（p < 0.001）和肝脏重量（p < 0.001），并改善肝功能。对于小鼠和细胞模型，TSPJ均减少脂质积累（p = 0.05），并抑制脂肪生成基因Acaca（p < 0.001；p = 0.02）、Fasn（p = 0.008；p = 0.001）和Scd1（p = 0.05；p = 0.05）的表达。根据非靶向代谢组学分析，磷脂酰胆碱（PC）是受TSPJ影响的主要脂质种类。PLD1是miR-1a-3p的下游靶点，是TSPJ调节脂质代谢的关键所在。当模型敲低miR-1a-3p时，TSPJ的疗效消失。
结论
TSPJ通过上调miR-1a-3p减轻肝细胞脂肪变性，miR-1a-3p抑制PLD1以减少PC水解，最终减少肝脏脂质积累。
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