Magnolol Alleviates Inflammatory Responses and Lipid Accumulation by AMP-Activated Protein Kinase-Dependent Peroxisome Proliferator-Activated Receptor α Activation.
Magnolol Alleviates Inflammatory Responses and Lipid Accumulation by AMP-Activated Protein Kinase-Dependent Peroxisome Proliferator-Activated Receptor α Activation.
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厚朴酚通过 AMP 激活蛋白激酶依赖性过氧化物酶体增殖物激活受体 α 激活减轻炎症反应和脂质积累
DOI：
10.3389/fimmu.2018.00147
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发表时间：
2018
影响因子：
7.3
通讯作者：
Liu G
中科院分区：
文献类型：
--
作者：
Tian Y;Feng H;Han L;Wu L;Lv H;Shen B;Li Z;Zhang Q;Liu G
厚朴酚（Magnolol， MG）是从厚朴中分离得到的一种木质素，具有抗真菌、抗癌、抗氧化、保肝等多种生物学功能。本研究旨在评估MG对油酸（OA）诱导的HepG2细胞和泰洛沙酚（Ty）诱导的高脂血症小鼠模型的肝脂肪变性和炎症损伤的保护作用。我们的研究结果表明，MG可以有效抑制oa刺激的肿瘤坏死因子α (TNF-α)分泌、活性氧的产生和甘油三酯（TG）的积累。进一步研究表明，MG可显著抑制oa活化的丝裂原活化蛋白激酶（MAPK）和核因子κB （NF-κB）信号通路，并且可以通过细胞外调节蛋白激酶和c-Jun n-末端激酶（分别为U0126和SP600125）抑制剂预处理这些炎症反应。此外，MG显著上调过氧化物酶体增殖物活化受体α (PPARα)易位，降低甾醇调节元件结合蛋白1c （SREBP-1c）蛋白的合成和排泄，这两者都依赖于单磷酸腺苷（AMP）活化蛋白激酶（AMPK）、乙酰辅酶a羧化酶和AKT激酶（AKT）的磷酸化。然而，MG暂停了PPARα表达的激活，因此通过LY294002和化合物c （AKT和AMPK的特异性抑制剂）预处理被阻断。此外，MG明显减轻血清TG和总胆固醇释放；AKT、AMPK、PPARα表达上调；抑制SREBP-1c生成；减轻ty诱导的高脂血症小鼠的肝脂肪变性和血脂异常。综上所述，这些结果表明MG对脂肪变性、高脂血症具有保护作用，其潜在机制可能与AKT/AMPK/PPARα激活和MAPK/NF-κB/SREBP-1c抑制密切相关。
Magnolol (MG) is a kind of lignin isolated from Magnolia officinalis, which serves several different biological functions, such as antifungal, anticancer, antioxidant, and hepatoprotective functions. This study aimed to evaluate the protective effect of MG against oleic acid (OA)-induced hepatic steatosis and inflammatory damage in HepG2 cells and in a tyloxapol (Ty)-induced hyperlipidemia mouse model. Our findings indicated that MG can effectively inhibit OA-stimulated tumor necrosis factor α (TNF-α) secretion, reactive oxygen species generation, and triglyceride (TG) accumulation. Further study manifested that MG significantly suppressed OA-activated mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways and that these inflammatory responses can be negated by pretreatment with inhibitors of extracellular regulated protein kinase and c-Jun N-terminal kinase (U0126 and SP600125, respectively). In addition, MG dramatically upregulated peroxisome proliferator-activated receptor α (PPARα) translocation and reduced sterol regulatory element-binding protein 1c (SREBP-1c) protein synthesis and excretion, both of which are dependent upon the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), acetyl-CoA carboxylase, and AKT kinase (AKT). However, MG suspended the activation of PPARα expression and was thus blocked by pretreatment with LY294002 and compound c (specific inhibitors of AKT and AMPK). Furthermore, MG clearly alleviated serum TG and total cholesterol release; upregulated AKT, AMPK, and PPARα expression; suppressed SREBP-1c generation; and alleviated hepatic steatosis and dyslipidemia in Ty-induced hyperlipidemia mice. Taken together, these results suggest that MG exerts protective effects against steatosis, hyperlipidemia, and the underlying mechanism, which may be closely associated with AKT/AMPK/PPARα activation and MAPK/NF-κB/SREBP-1c inhibition.