Qu Li-Li, Yu Bin, Li Zheng, Jiang Wen-Xiao, Jiang Jian-Dong, Kong Wei-Jia
State Key Laboratory of Bioactive Natural Products and Function, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Phytother Res. 2016 Mar;30(3):402-11. doi: 10.1002/ptr.5541. Epub 2015 Dec 4.
This study was designed to investigate the antioxidative, antiinflammatory and metabolism-regulating effects of gastrodin (GSTD) in the treatment of nonalcoholic fatty liver disease (NAFLD). Oleic acid (OA) was used to induce steatosis in HL-7702 cells; a high-fat or high-fat and high-cholesterol diet was used to induce NAFLD in mice and rats. Our results showed that GSTD significantly increased hepatic superoxide dismutase (SOD) but decreased reactive oxygen species (ROS)/malondialdehyde (MDA) and reduced the mRNA levels of proinflammatory cytokines both in vitro and in vivo. GSTD promoted the phosphorylation of nuclear factor erythroid-2-related factor-2 (Nrf2) at serine (Ser) 40, stimulated its nuclear translocation and increased hepatic expression of heme oxygenase-1 (HO-1). GSTD activated AMP-activated protein kinase (AMPK), suppressed hepatic steatosis, lowered serum triglyceride (TG)/glucose and decreased body weight gain in animals with NAFLD. The stimulating effects of GSTD on the Nrf2 pathway as well as its antioxidative/antiinflammatory activities were abolished by compound C in OA-treated HL-7702 cells. In summary, our results demonstrate that GSTD activates the AMPK/Nrf2 pathway, ameliorates oxidative stress/proinflammatory response and improves lipid metabolism in NAFLD. Our findings may support the future clinical application of GSTD for the treatment of NAFLD to reduce hepatic steatosis, oxidative stress and proinflammatory response.
本研究旨在探讨天麻素（GSTD）在治疗非酒精性脂肪性肝病（NAFLD）中的抗氧化、抗炎和代谢调节作用。采用油酸（OA）诱导HL-7702细胞脂肪变性；采用高脂或高脂高胆固醇饮食诱导小鼠和大鼠发生NAFLD。我们的结果表明，GSTD显著增加肝脏超氧化物歧化酶（SOD），但降低活性氧（ROS）/丙二醛（MDA），并在体外和体内降低促炎细胞因子的mRNA水平。GSTD促进核因子红细胞2相关因子2（Nrf2）丝氨酸（Ser）40位点的磷酸化，刺激其核转位，并增加血红素加氧酶-1（HO-1）的肝脏表达。GSTD激活AMP活化蛋白激酶（AMPK），抑制肝脏脂肪变性，降低血清甘油三酯（TG）/血糖，并减少NAFLD动物的体重增加。在OA处理的HL-7702细胞中，化合物C消除了GSTD对Nrf2途径的刺激作用及其抗氧化/抗炎活性。总之，我们的结果表明，GSTD激活AMPK/Nrf2途径，改善氧化应激/促炎反应，并改善NAFLD中的脂质代谢。我们的发现可能支持GSTD未来在临床上用于治疗NAFLD，以减少肝脏脂肪变性、氧化应激和促炎反应。
