Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
J Nat Med. 2018 Jun;72(3):655-666. doi: 10.1007/s11418-018-1199-5. Epub 2018 Mar 14.
Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-A mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA. In KK-A mice, S. baicalensis extract showed a decreased effect on serum and hepatic triglycerides, total cholesterols, and free fatty acid (FFA) levels after 8 weeks of treatment. In OA-induced NAFLD rats, 18 days of treatment with baicalin significantly inhibited hepatic lipid accumulation, attenuating hepatocyte hypertrophy, vacuolization and necrosis. S. baicalensis and baicalin treatment significantly suppressed the sterol regulatory element binding protein-1c (SREBP-1c) transcriptional program with downregulation of gene and protein expression of SREBP-1c (both precursor and mature fraction) and acetyl-CoA carboxylase, fatty acid synthase and stearoyl-CoA desaturase, and upregulation of AMP-activated protein kinase (AMPK), carnitine palmitoyl transferase 1 and nuclear respiratory factor 2 in the liver. Furthermore, activation of AMPK by baicalin was observed to be relative to the increase in phosphorylation of calmodulin-dependent protein kinase kinase. Taken together, S. baicalensis conferred preventive effects against FFA-induced lipotoxicity through the AMPK-mediated SREBP signaling pathway.
黄芩被报道可改善高脂肪饮食诱导的肝功能障碍的脂质代谢，但直接证据很少。本研究旨在探索黄芩及其主要成分黄芩苷对肝脂毒性的作用和机制。使用 KK-A 小鼠和乳清酸（OA）诱导的非酒精性脂肪性肝病（NAFLD）大鼠来评估脂质代谢调节作用。使用油酸钠诱导的甘油三酯积累 HepG2 细胞进行机制研究，用或不用化合物 C 或 STO-609 预处理，或用肝激酶 B1（LKB1）siRNA 转染。在 KK-A 小鼠中，黄芩提取物在治疗 8 周后对血清和肝甘油三酯、总胆固醇和游离脂肪酸（FFA）水平的降低作用。在 OA 诱导的 NAFLD 大鼠中，18 天的黄芩苷治疗显著抑制肝脂质积累，减轻肝细胞肥大、空泡化和坏死。黄芩和黄芩苷治疗显著抑制固醇调节元件结合蛋白-1c（SREBP-1c）转录程序，下调 SREBP-1c 的基因和蛋白表达（前体和成熟片段）以及乙酰辅酶 A 羧化酶、脂肪酸合酶和硬脂酰辅酶 A 去饱和酶，并上调 AMP 激活的蛋白激酶（AMPK）、肉碱棕榈酰转移酶 1 和核呼吸因子 2 在肝脏中。此外，黄芩苷对 AMPK 的激活被观察到与钙调蛋白依赖性蛋白激酶激酶的磷酸化增加有关。总之，黄芩通过 AMPK 介导的 SREBP 信号通路对 FFA 诱导的脂毒性发挥预防作用。
