Maharajan Nagarajan, Vijayakumar Karthikeyan A, Cho Gwang-Won
Department of Otorhinolaryngology - Head and Neck Surgery, University of Maryland School of Medicine, 21201, Baltimore, MD, USA.
Department of Biological Science, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, 61452, Gwangju, South Korea; The Basic Science Institute of Chosun University, Chosun University, 61452, Gwangju, South Korea.
Biochem Biophys Res Commun. 2025 Jan;744:151216. doi: 10.1016/j.bbrc.2024.151216. Epub 2024 Dec 20.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease associated with type 2 diabetes, which doubles the risk of developing this condition. Various flavonoid compounds have a positive effect on lipid metabolism, inflammation, and insulin resistance and can contribute to slowing down the progression of MASLD. In the current study, we investigated the biological effects of Licochalcone D (Lico D), a flavonoid, in a metabolic disease model. Oil Red O staining, quantitative real-time polymerase chain reaction, and western blotting were performed. For in vivo experiments, we used high-fat diet (60 %) plus low-dose streptozotocin (30 mg/kg; 5 days; intraperitoneal)-induced metabolic disease mouse model and evaluated lipid metabolism. We observed that Lico D reduced lipid accumulation and increased lipid metabolism both in vitro and in vivo. Additionally, we identified that the AMP-activated protein kinase and Sirtuin 1 pathways were activated in the mouse liver and hepatic steatosis cell model. In silico analysis revealed that Lico D passes the "Lipinski Rule of Five," which indicates drug-likeness properties. In conclusion, our findings highlight the role of Lico D in improving metabolic dysfunction-associated steatotic liver disease.
代谢功能障碍相关脂肪性肝病（MASLD）是一种与2型糖尿病相关的常见慢性肝病，患2型糖尿病会使发生这种疾病的风险加倍。多种黄酮类化合物对脂质代谢、炎症和胰岛素抵抗具有积极作用，有助于减缓MASLD的进展。在本研究中，我们在一种代谢疾病模型中研究了黄酮类化合物地锦草查耳酮D（Lico D）的生物学效应。进行了油红O染色、定量实时聚合酶链反应和蛋白质印迹分析。对于体内实验，我们使用高脂饮食（60%）加低剂量链脲佐菌素（30 mg/kg；5天；腹腔注射）诱导的代谢疾病小鼠模型，并评估脂质代谢。我们观察到，Lico D在体外和体内均能减少脂质积累并增强脂质代谢。此外，我们发现，在小鼠肝脏和肝脂肪变性细胞模型中，AMP激活的蛋白激酶和沉默调节蛋白1通路被激活。计算机模拟分析表明，Lico D符合“Lipinski五规则”，这表明其具有类药物特性。总之，我们的研究结果突出了Lico D在改善代谢功能障碍相关脂肪性肝病方面的作用。
