Cai Yuan, Huang Rong, Lin Tianfeng, Yang Leyi, Zhou Chang, Li Yumiao, Liu Bin, Dong Shifen, Jiang Yanyan
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
Molecules. 2025 Sep 12;30(18):3727. doi: 10.3390/molecules30183727.
() exhibits hypolipidemic effects and shows great potential for application in lipid-lowering drugs and healthcare products. This study aimed to investigate the mechanism underlying the hypolipidemic effects of the alkaloid fraction of (AFN). Animal experiments demonstrated that AFN significantly reduced blood lipid levels and ameliorated liver damage in hyperlipidemic mice. RNA-seq analysis identified 26 reverse-regulated differentially expressed genes (DEGs), which were primarily involved in the PPAR signaling pathway, fat digestion and absorption, and fatty acid degradation. Using UPLC-MS, 30 plasma-absorbed components were identified, including 13 prototype alkaloids. Among these, three key active components-nuciferine, -nornuciferine, and -methylisococlaurine-were screened via network topology analysis. Molecular docking revealed strong binding affinities between these compounds and key targets. The results showed that -methylisococlaurine bound to and with strong affinity, while nuciferine and -nornuciferine bound to and . RT-qPCR results confirmed that AFN modulates the expression of , , , , , , and . These findings suggest that AFN exerts its hypolipidemic effects through multi-component, multi-target, and multi-pathway mechanisms.
（）具有降血脂作用，在降脂药物和保健品中具有巨大的应用潜力。本研究旨在探讨（AFN）生物碱组分降血脂作用的潜在机制。动物实验表明，AFN显著降低高脂血症小鼠的血脂水平并改善肝损伤。RNA测序分析确定了26个反向调节的差异表达基因（DEG），这些基因主要参与PPAR信号通路、脂肪消化吸收和脂肪酸降解。使用超高效液相色谱-质谱联用技术，鉴定出30种血浆吸收成分，包括13种原型生物碱。其中，通过网络拓扑分析筛选出三种关键活性成分——荷叶碱、去甲荷叶碱和甲基异紫堇杷灵。分子对接显示这些化合物与关键靶点之间具有很强的结合亲和力。结果表明，甲基异紫堇杷灵与和具有很强的亲和力，而荷叶碱和去甲荷叶碱与和结合。实时定量PCR结果证实，AFN调节、、、、、和的表达。这些发现表明，AFN通过多成分、多靶点和多途径机制发挥其降血脂作用。
