Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China (mainland).
Liaoning Institute for Drug Control, Shenyang, Liaoning, China (mainland).
Med Sci Monit. 2017 Nov 24;23:5599-5612. doi: 10.12659/msm.907530.
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the form of triglycerides. The incidence of NAFLD and hyperlipidemia, with their associated risks of end-stage liver and cardiovascular diseases, is increasing rapidly. This study aimed to investigate the effects of scutellarin on the experimental NAFLD in high-fat diet fed and chronic stress rats, and its possible mechanism. MATERIAL AND METHODS Sprague-Dawley rats were fed with high-fat diet and subjected to chronic stress for 12 weeks, and administered orally with scutellarin for 4 weeks (n=8), and then blood and livers were harvested for analyzing. Enzyme activity assay, immunofluorescence, Western blot, and quantitative RT-PCR were performed to analyze the factors of the oxidant/antioxidant system and pathway. RESULTS After the high-fat diet and chronic stress administration for 12 weeks, serum and liver lipid metabolism of treatment groups with the different doses of SCU effectively improved and the degree of oxidative damage reduced. Using Western blot assay and immunofluorescence (IF) staining assay, Nrf2, HO-1, and PI3K, and AKT proteins significantly increased after SCU treatment for 4 weeks (P<0.01). The hepatic mRNA expression of HO-1, NQO1, and Nrf2 in SCU treatment groups was upregulated significantly through quantitative RT-PCR assay (P<0.05). However, compared to the positive control group, no difference was detected in the SCU (100 or 300 mg/kg) groups (P>0.05). These results indicate that SCU protects against NAFLD in rats via attenuation of oxidative stress. CONCLUSIONS The antioxidant effects of SCU on NAFLD are possibly dependent on PI3K/AKT activation with subsequent Nrf2 nuclear translocation, which increases expression of HO-1 and NQO1. We therefore suggest that breviscapine may be a potentially useful therapeutic strategy for NAFLD and hyperlipidemia.
非酒精性脂肪性肝病（NAFLD）是一种以甘油三酯形式过度脂肪堆积为特征的疾病。NAFLD 和高脂血症的发病率及其与终末期肝病和心血管疾病相关的风险正在迅速增加。本研究旨在探讨野黄芩苷对高脂饮食喂养和慢性应激大鼠实验性 NAFLD 的影响及其可能的机制。
Sprague-Dawley 大鼠给予高脂饮食并进行 12 周慢性应激，同时给予野黄芩苷灌胃 4 周（n=8），然后采血和取肝进行分析。酶活性测定、免疫荧光、Western blot 和定量 RT-PCR 用于分析氧化/抗氧化系统和途径的因素。
经过 12 周高脂饮食和慢性应激给药后，不同剂量 SCU 的血清和肝脏脂质代谢得到有效改善，氧化损伤程度降低。Western blot 检测和免疫荧光（IF）染色检测显示，SCU 治疗 4 周后 Nrf2、HO-1 和 PI3K、AKT 蛋白显著增加（P<0.01）。通过定量 RT-PCR 检测，SCU 治疗组肝组织 HO-1、NQO1 和 Nrf2 的 mRNA 表达明显上调（P<0.05）。然而，与阳性对照组相比，SCU（100 或 300 mg/kg）组没有差异（P>0.05）。这些结果表明，SCU 通过减轻氧化应激来保护大鼠的 NAFLD。
SCU 对 NAFLD 的抗氧化作用可能依赖于 PI3K/AKT 激活，随后 Nrf2 核转位，增加 HO-1 和 NQO1 的表达。因此，我们认为灯盏花素可能是治疗 NAFLD 和高脂血症的一种潜在有效治疗策略。
