Core Research Program 1515, Key Laboratory for Food Science and Biotechnology of Hunan Province, College of Food Science and Technology, Hunan Agricultural University, Changsha, China.
The United Graduate School of Agricultural Sciences, Faculty of Agriculture, Kagoshima University, Korimoto 1-21-24, Kagoshima, Japan.
Acta Biochim Biophys Sin (Shanghai). 2019 Apr 1;51(4):365-374. doi: 10.1093/abbs/gmz014.
Momordica grosvenori is a valuable edible plant with medicinal purposes, and it is widely used in medicated diets and traditional Chinese medicine in Asia. Mogroside V (MV), the main bioactive component from M. grosvenori, is commonly used as a natural sweetener. M. grosvenori extracts have been reported to exert potent anti-inflammatory property, however the underlying molecular mechanism still remains unknown. In the present study, the biological effect of MV in inflammation was investigated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The ELISA and western blot analysis results showed that MV significantly inhibited LPS-induced prostaglandin E2 (PGE2) production and cyclooxygenase-2 (COX-2) expression. MV markedly decreased the phosphorylation of IκB-α, increased IκB-α, and reduced nuclear p-65 and C/EBPδ. Furthermore, MV attenuated LPS-induced phosphorylation of MAPKs and AKT1, and only the phosphorylation status of AKT1 was found to be consistent with the expression trend of COX-2. Moreover, MV reduced ROS level and restored overexpressed HO-1 and AP-1 to basal level, which can be markedly reversed by AKT1 inhibitor LY294002. These results revealed that AKT1 plays a key role in LPS-induced COX-2 expression, and acts as a mediator to keep the redox balance in LPS-stimulated RAW264.7 cells. MV exerts anti-inflammatory property by blocking AKT1-mediated NF-κB and C/EBPδ activation, ROS generation and AP-1/ HO-1 expression. Therefore, the present study indicated that MV has a significant chemopreventive effect on the inflammatory lesions and suggested that AKT1 is a potential specific target of MV for relieving inflammation.
罗汉果是一种具有药用价值的珍贵食用植物，在亚洲被广泛应用于药膳和中药。罗汉果苷 V（MV）是罗汉果的主要生物活性成分，通常用作天然甜味剂。已有报道称，罗汉果提取物具有强大的抗炎作用，但其中的分子机制尚不清楚。在本研究中，研究人员考察了 MV 在脂多糖（LPS）刺激的 RAW264.7 细胞中的抗炎作用。ELISA 和 Western blot 分析结果表明，MV 可显著抑制 LPS 诱导的前列腺素 E2（PGE2）产生和环氧化酶-2（COX-2）表达。MV 明显降低了 IκB-α 的磷酸化，增加了 IκB-α，并减少了核 p-65 和 C/EBPδ。此外，MV 减弱了 LPS 诱导的 MAPKs 和 AKT1 的磷酸化，并且只有 AKT1 的磷酸化状态与 COX-2 的表达趋势一致。此外，MV 降低了 ROS 水平，并将过表达的 HO-1 和 AP-1 恢复到基础水平，而 AKT1 抑制剂 LY294002 可显著逆转这一现象。这些结果表明，AKT1 在 LPS 诱导的 COX-2 表达中起关键作用，并且作为一种介质来维持 LPS 刺激的 RAW264.7 细胞中的氧化还原平衡。MV 通过阻断 AKT1 介导的 NF-κB 和 C/EBPδ 激活、ROS 生成和 AP-1/HO-1 表达来发挥抗炎作用。因此，本研究表明 MV 对炎症损伤具有显著的化学预防作用，并提示 AKT1 是 MV 缓解炎症的潜在特异性靶标。
