School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.
Int J Mol Sci. 2024 Oct 9;25(19):10855. doi: 10.3390/ijms251910855.
Leonurine is a natural product unique to the Lamiaceae plant , and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 (), Spermine Synthase (), AP-1 Transcription Factor Subunit (), Oxysterol Binding Protein Like 5 (), and FK506 binding protein 5 () in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis.
汉黄芩素是唇形科植物特有的天然产物，因其具有抗氧化应激、抗细胞凋亡、抗纤维化和代谢调节作用而受到关注。此外，它通过多种生物学机制在预防和治疗非酒精性脂肪性肝病（NAFLD）方面发挥着重要作用，但作用机制仍有待阐明。因此，本研究旨在初步探讨汉黄芩素在 NAFLD 中的作用机制。小鼠随机分为四组：正常对照组（NC）、模型组（M）、汉黄芩素治疗组（LH）和非诺贝特治疗组（FB）。采用高脂肪高糖饮食（HFHSD）诱导 12 周建立 NAFLD 模型，12 周后观察肝脏病理变化和生化指标。转录组分析结果表明，汉黄芩素干预逆转了高脂肪高糖饮食诱导的肝脏组织中脂质代谢相关基因如硬脂酰辅酶 A 去饱和酶 1（）、精脒合成酶（）、AP-1 转录因子亚基（）、氧化固醇结合蛋白样 5（）和 FK506 结合蛋白 5（）的变化。京都基因与基因组百科全书（KEGG）富集分析结果提示，汉黄芩素可能通过 AMP 激活的蛋白激酶（AMPK）信号通路发挥其降脂作用。肝脏脂质组学分析表明，汉黄芩素可以改变与脂肪酸（FAs）和甘油磷脂（GPs）相关的脂质分子的丰度，如 TxB3、肉碱 C12-OH、肉碱 C18:1-OH 和 LPC（20:3/0:0）。分子生物学实验和分子对接技术验证了汉黄芩素可能通过α-1A 肾上腺素能受体（ADRA1a）/AMPK/SCD1 轴改善肝脏脂质代谢。综上所述，本研究通过 ADRA1a/AMPK/SCD1 轴抑制肝内脂质合成探讨了汉黄芩素改善 NAFLD 的作用机制。
