Tai Cheng-Jeng, Choong Chen-Yen, Shi Yeu-Ching, Lin Yu-Chun, Wang Chia-Woei, Lee Bao-Hong, Tai Chen-Jei
Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medicine University Hospital, Taipei 11031, Taiwan.
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Molecules. 2016 Feb 25;21(3):269. doi: 10.3390/molecules21030269.
Advanced glycation end products (AGEs) signal through the receptor for AGE (RAGE), which can lead to hepatic fibrosis in hyperglycemia and hyperlipidemia. We investigated the inhibitory effect of aqueous extracts from Solanum nigrum (AESN) on AGEs-induced RAGE signaling and activation of hepatic stellate cells (HSCs) and hyperglycemia induced by high-fat diet with ethanol.
An animal model was used to evaluate the anti-hepatic fibrosis activity of AESN in rats fed a high-fat diet (HFD; 30%) with ethanol (10%). Male Wistar rats (4 weeks of age) were randomly divided into four groups (n = 6): (1) control (basal diet); (2) HFD (30%) + ethanol (10%) (HFD/ethanol); (3) HFD/ethanol + AESN (100 mg/kg, oral administration); and (4) HFD/ethanol + pioglitazone (10 mg/kg, oral administration) and treated with HFD for 6 months in the presence or absence of 10% ethanol in dietary water.
We found that AESN improved insulin resistance and hyperinsulinemia, and downregulated lipogenesis via regulation of the peroxisome proliferator-activated receptor α (PPARα), PPARγ co-activator (PGC-1α), carbohydrate response element-binding protein (ChREBP), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) mRNA levels in the liver of HFD/ethanol-treated rats. In turn, AESN may delay and inhibit the progression of hepatic fibrosis, including α-smooth muscle actin (α-SMA) inhibition and MMP-2 production.
These results suggest that AESN may be further explored as a novel anti-fibrotic strategy for the prevention of liver disease.
晚期糖基化终末产物（AGEs）通过AGE受体（RAGE）发出信号，这可导致高血糖和高血脂状态下的肝纤维化。我们研究了龙葵水提取物（AESN）对AGEs诱导的RAGE信号传导以及肝星状细胞（HSC）激活和高脂饮食加乙醇诱导的高血糖的抑制作用。
使用动物模型评估AESN对喂食高脂饮食（HFD；30%）加乙醇（10%）的大鼠的抗肝纤维化活性。雄性Wistar大鼠（4周龄）随机分为四组（n = 6）：（1）对照组（基础饮食）；（2）HFD（30%）+乙醇（10%）（HFD/乙醇组）；（3）HFD/乙醇+AESN（100 mg/kg，口服）；以及（4）HFD/乙醇+吡格列酮（10 mg/kg，口服），在饮食水中存在或不存在10%乙醇的情况下用HFD处理6个月。
我们发现AESN改善了胰岛素抵抗和高胰岛素血症，并通过调节过氧化物酶体增殖物激活受体α（PPARα）、PPARγ共激活因子（PGC-1α）、碳水化合物反应元件结合蛋白（ChREBP）、乙酰辅酶A羧化酶（ACC）和脂肪酸合酶（FAS）在HFD/乙醇处理大鼠肝脏中的mRNA水平来下调脂肪生成。反过来，AESN可能延迟并抑制肝纤维化的进展，包括抑制α平滑肌肌动蛋白（α-SMA）和产生基质金属蛋白酶-2（MMP-2）。
这些结果表明，AESN可能作为预防肝病的新型抗纤维化策略被进一步探索。
