Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
Molecules. 2024 Jun 3;29(11):2630. doi: 10.3390/molecules29112630.
Non-alcoholic fatty liver disease (NAFLD) is a significant hepatic condition that has gained worldwide attention. Kaempferol (Kae), renowned for its diverse biological activities, including anti-inflammatory, antioxidant, anti-aging, and cardio-protective properties, has emerged as a potential therapeutic candidate for non-alcoholic steatohepatitis (NASH). Despite its promising therapeutic potential, the precise underlying mechanism of Kae's beneficial effects in NASH remains unclear. Therefore, this study aims to clarify the mechanism by conducting comprehensive in vivo and in vitro experiments.
In this study, a murine model of non-alcoholic steatohepatitis (NASH) was established by feeding C57BL/6 female mice a high-fat diet for 12 weeks. Kaempferol (Kae) was investigated for its ability to modulate systemic inflammatory responses and lipid metabolism in this model (20 mg/kg per day). Notably, Kae significantly reduced the expression of NLRP3-ASC/TMS1-Caspase 3, a crucial mediator of liver tissue inflammation. Additionally, in a HepG2 cell model induced with palmitic acid/oleic acid (PA/OA) to mimic NASH conditions, Kae demonstrated the capacity to decrease lipid droplet accumulation and downregulate the expression of NLRP3-ASC/TMS1-Caspase 3 (20 µM and the final concentration to 20 nM). These findings suggest that Kae may hold therapeutic potential in the treatment of NASH by targeting inflammatory and metabolic pathways.
These findings suggest that kaempferol holds potential as a promising therapeutic intervention for ameliorating non-alcoholic fatty liver disease (NAFLD).
非酒精性脂肪性肝病（NAFLD）是一种重要的肝脏疾病，已引起全球关注。山奈酚（Kae）以其多种生物活性而闻名，包括抗炎、抗氧化、抗衰老和心脏保护作用，已成为非酒精性脂肪性肝炎（NASH）的潜在治疗候选药物。尽管 Kae 在 NASH 中的治疗潜力巨大，但 Kae 对 NASH 有益作用的确切潜在机制尚不清楚。因此，本研究旨在通过进行全面的体内和体外实验来阐明其机制。
本研究通过用高脂肪饮食喂养 C57BL/6 雌性小鼠 12 周来建立非酒精性脂肪性肝炎（NASH）的小鼠模型。研究了山奈酚（Kae）在该模型中调节全身炎症反应和脂质代谢的能力（每天 20mg/kg）。值得注意的是，Kae 可显著降低 NLRP3-ASC/TMS1-Caspase 3 的表达，这是肝脏组织炎症的关键介质。此外，在棕榈酸/油酸（PA/OA）诱导的 HepG2 细胞模型中模拟 NASH 条件下，Kae 显示出减少脂滴积累和下调 NLRP3-ASC/TMS1-Caspase 3 表达的能力（20µM 和最终浓度为 20nM）。这些发现表明，Kae 可能通过靶向炎症和代谢途径在治疗 NASH 方面具有治疗潜力。
这些发现表明山奈酚具有作为改善非酒精性脂肪性肝病（NAFLD）的有前途的治疗干预的潜力。
