Zhu Wenrui, Xu Hongfeng, Yan Rui, Qiu Luqi, Wang Guojun, Zhu Yantao
Department of Traditional Chinese Medicine, Shaoxing Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Shaoxing, China.
Department of Clinical Pharmacy, Shaoxing Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Shaoxing, China.
Histol Histopathol. 2025 Mar 18:18907. doi: 10.14670/HH-18-907.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent hepatic disorder with high morbidity and mortality. Licochalcone A (LiA) exhibits significant therapeutic efficacy in obesity through diverse pharmacological mechanisms. This study aimed to explore the efficacy and underlying mechanism of LiA in attenuating MASLD, which requires further investigation.
Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks to establish a MASLD mouse model. The lipid level and liver function of mice were evaluated by the levels of TG, TC, ALT, and AST. H&E staining and Oil Red O staining were used to evaluate the pathological changes and lipid deposits in the liver. Lipid metabolism and PPARα/CPT1α signaling pathway-related genes were detected.
LiA effectively reduced weight and improved glucose tolerance and insulin resistance in MASLD mice. LiA treatment significantly reduced lipid accumulation in HFD-induced mice. In addition, bioinformatics analysis, molecular docking, and cellular thermal shift assays further indicated that LiA alleviated MASLD by upregulating PPARα. Furthermore, the protective effect of LiA on lipid accumulation and hepatic steatosis was abolished by PPARα inhibitor (GW7461) pretreatment in MASLD mice.
This study demonstrated that LiA ameliorates the lipid metabolism disorder in MASLD mice by upregulating the PPARα/CPT1α signaling pathway.
代谢功能障碍相关脂肪性肝病（MASLD）是最常见的肝脏疾病，发病率和死亡率都很高。甘草查尔酮A（LiA）通过多种药理机制在肥胖症中显示出显著的治疗效果。本研究旨在探讨LiA在减轻MASLD方面的疗效及潜在机制，这需要进一步研究。
雄性C57BL/6小鼠喂食高脂饮食（HFD）12周以建立MASLD小鼠模型。通过甘油三酯（TG）、总胆固醇（TC）、谷丙转氨酶（ALT）和谷草转氨酶（AST）水平评估小鼠的血脂水平和肝功能。采用苏木精-伊红（H&E）染色和油红O染色评估肝脏的病理变化和脂质沉积。检测脂质代谢和过氧化物酶体增殖物激活受体α（PPARα）/肉碱棕榈酰转移酶1α（CPT1α）信号通路相关基因。
LiA有效减轻了MASLD小鼠的体重，改善了葡萄糖耐量和胰岛素抵抗。LiA治疗显著减少了高脂饮食诱导小鼠的脂质积累。此外，生物信息学分析、分子对接和细胞热位移分析进一步表明，LiA通过上调PPARα减轻MASLD。此外，在MASLD小鼠中，PPARα抑制剂（GW7461）预处理消除了LiA对脂质积累和肝脂肪变性的保护作用。
本研究表明，LiA通过上调PPARα/CPT1α信号通路改善MASLD小鼠的脂质代谢紊乱。
