Department of Pharmacology, College of Korean Medicine, Sangji University, Wonju, Gangwon-do, 26339, Republic of Korea.
Department of Agro-Industrial Technology, Lambung Mangkurat University, Banjarbaru, Indonesia.
Sci Rep. 2022 Mar 9;12(1):4154. doi: 10.1038/s41598-022-07937-3.
Nonalcoholic fatty liver disease (NAFLD) is usually correlated with metabolic diseases, such as obesity, insulin resistance, and hyperglycemia. Herein, we investigated the inhibitory effects and underlying governing mechanism of clitorin in a western diet (WD)-induced hepatic steatosis mouse model, and in oleic acid-stimulated HepG2 cells. Male C57BL/6 mice were fed a normal diet, WD, WD + 10 or 20 mg/kg orlistat, and WD + 10 or 20 mg/kg clitorin. HepG2 cells were treated with 1 mM oleic acid to induce lipid accumulation with or without clitorin. Clitorin significantly alleviated body weight gain and hepatic steatosis features (NAFLD activity score, micro-, and macro-vesicular steatosis) in WD-induced hepatic steatosis mice. Additionally, clitorin significantly decreased protein expressions of sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα) in WD-induced hepatic steatosis mice. Moreover, clitorin significantly diminished the mRNA levels of SREBP1, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and enhanced the mRNA levels of peroxisome proliferator-activated receptor α (PPARα) and carnitine palmitoyltranserase-1 (CTP-1), as well as adenosine monophosphate-activated protein kinase (AMPK) in the liver of WD-induced hepatic steatosis mice and oleic acid-stimulated HepG2 cells. Overall, our findings demonstrated that clitorin can be a potentially efficacious candidate for NAFLD management.
非酒精性脂肪性肝病（NAFLD）通常与代谢疾病相关，如肥胖、胰岛素抵抗和高血糖。在此，我们研究了 Clitorin 在西式饮食（WD）诱导的肝脂肪变性小鼠模型和油酸刺激的 HepG2 细胞中的抑制作用及其潜在的调控机制。雄性 C57BL/6 小鼠分别喂食正常饮食、WD、WD+10 或 20mg/kg 奥利司他和 WD+10 或 20mg/kg Clitorin。用 1mM 油酸处理 HepG2 细胞以诱导脂滴积累，同时加入或不加入 Clitorin。Clitorin 显著减轻 WD 诱导的肝脂肪变性小鼠的体重增加和肝脂肪变性特征（NAFLD 活性评分、微泡和大泡脂肪变性）。此外，Clitorin 显著降低 WD 诱导的肝脂肪变性小鼠中固醇调节元件结合蛋白 1（SREBP1）、过氧化物酶体增殖物激活受体 γ（PPARγ）和 CCAAT/增强子结合蛋白α（C/EBPα）的蛋白表达。此外，Clitorin 显著降低 WD 诱导的肝脂肪变性小鼠肝脏中 SREBP1、乙酰辅酶 A 羧化酶（ACC）、脂肪酸合酶（FAS）和羟甲基戊二酰辅酶 A 还原酶（HMGCR）的 mRNA 水平，同时提高过氧化物酶体增殖物激活受体α（PPARα）和肉碱棕榈酰转移酶-1（CPT-1）以及腺苷单磷酸激活蛋白激酶（AMPK）的 mRNA 水平。总之，我们的研究结果表明，Clitorin 可能是治疗 NAFLD 的有效候选药物。
