Hwang Kyung-A, Hwang Yu-Jin, Kim Ga Ram, Choe Jeong-Sook
Department of Agrofood Resources, National Academy of Agricultural Science, RDA, Wanju-Gun, Jeollabuk-do, 565-851, Republic of Korea.
BMC Complement Altern Med. 2015 Oct 5;15:347. doi: 10.1186/s12906-015-0871-5.
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease that is strongly associated with obesity and dysregulation of insulin in the liver. However, currently no pharmacological agents have been established for the treatment of NAFLD. In this regard, we sought to evaluate the anti-NAFLD effects of Aralia elata (Miq) Seem (AE) extract and its ability to inhibit hepatic lipid accumulation and modulate cellular signaling in a high fat diet (HFD)-induced obese mouse model.
A model of hepatic steatosis in the HepG2 cells was induced by oleic acid. Intracellular lipid droplets were detected by Oil-Red-O staining, and the expression of sterol regulatory element-binding protein 1(SREBP-1), Fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC) 1 and 2, Peroxisome proliferator activated receptor-α (PPARα), and carnitine palmitoyl transferase 1(CPT-1) was analyzed by real time reverse transcription-Polymerase chain reaction (qRT-PCR). And glucose consumption was measured with commercial kit. Furthermore, Male C57BL/6 J mice were fed with HFD to induce NAFLD. Groups of mice were given plant extracts orally at 100 and 300 mg/kg at daily for 4 weeks. After 3 weeks of AE extract treatment, we performed oral glucose tolerance test (OGTT). Liver tissue was procured for histological examination, Phosphoinositide 3-kinase (PI3K) and Protein kinase B (PKB/Akt) activity.
In the present study, AE extract was shown to reduce hepatic lipid accumulation and significantly downregulate the level of lipogenic genes and upregulate the expression of lipolysis genes in HepG2 cells. And also, AE extract significantly increased the glucose consumption, indicating that AE extract improved insulin resistance. Subsequently, we confirmed the inhibitory activity of AE extract on NAFLD, in vivo. Treatment with AE extract significantly decreased body weight and the fasting glucose level, alleviated hyperinsulinism and hyperlipidemia, and reduced glucose levels, as determined by OGTT. Additionally, AE extract decreased PI3K and Akt activity.
Our results suggest that treatment with AE extract ameliorated NAFLD by inhibiting insulin resistance through activation of the Akt/GLUT4 pathway.
非酒精性脂肪性肝病（NAFLD）是一种常见的肝脏疾病，与肥胖及肝脏胰岛素调节异常密切相关。然而，目前尚未确立用于治疗NAFLD的药物。在这方面，我们试图在高脂饮食（HFD）诱导的肥胖小鼠模型中评估辽东楤木（Aralia elata (Miq) Seem，AE）提取物的抗NAFLD作用及其抑制肝脏脂质蓄积和调节细胞信号传导的能力。
用油酸诱导HepG2细胞发生肝脂肪变性。通过油红O染色检测细胞内脂滴，并采用实时逆转录-聚合酶链反应（qRT-PCR）分析固醇调节元件结合蛋白1（SREBP-1）、脂肪酸合酶（FAS）、乙酰辅酶A羧化酶（ACC）1和2、过氧化物酶体增殖物激活受体-α（PPARα）以及肉碱棕榈酰转移酶1（CPT-1）的表达。并用商业试剂盒测定葡萄糖消耗。此外，给雄性C57BL/6 J小鼠喂食HFD以诱导NAFLD。将小鼠分组，每天口服100和300 mg/kg的植物提取物，持续4周。在AE提取物治疗3周后，进行口服葡萄糖耐量试验（OGTT）。采集肝脏组织进行组织学检查、磷酸肌醇3激酶（PI3K）和蛋白激酶B（PKB/Akt）活性检测。
在本研究中，AE提取物可减少HepG2细胞中的肝脏脂质蓄积，并显著下调脂肪生成基因的水平，上调脂肪分解基因的表达。此外，AE提取物显著增加葡萄糖消耗，表明AE提取物改善了胰岛素抵抗。随后，我们在体内证实了AE提取物对NAFLD的抑制活性。AE提取物治疗可显著降低体重和空腹血糖水平，减轻高胰岛素血症和高脂血症，并降低OGTT测定的血糖水平。此外，AE提取物降低了PI3K和Akt活性。
我们的结果表明，AE提取物治疗通过激活Akt/GLUT4途径抑制胰岛素抵抗，从而改善NAFLD。
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