College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea.
Int J Mol Sci. 2021 Jan 19;22(2):965. doi: 10.3390/ijms22020965.
We have previously reported that phytochemicals from exhibit anti-inflammatory and neuroprotective effects by decreasing nitrite production and increasing nerve growth factor production. However, the exact mechanism underscoring these effects has not been revealed. In the present study, we aimed to explore the underlying anti-inflammatory mechanisms of and its phytochemicals. We studied various solvent fractions of and found the chloroform and hexane sub-fractions showed the most significant anti-neuroinflammatory effects in lipopolysaccharide (LPS)-activated murine microglia. Concomitantly, the terpenoids isolated from chloroform and hexane fractions showed similar anti-neuroinflammatory effects with significant inhibition of NO and reactive oxygen species production, and decreased protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase. Interestingly, these terpenoids inhibited the phosphorylation of c-Jun -terminal kinase (JNK), which further inhibited the production of pro-inflammatory mediators, including prostaglandin E2, tumor necrosis factor, and interleukins (IL-6 and IL-1β), with a potency greater than that of the well-known iNOS inhibitor NG-mono-methyl-L-arginine (L-NMMA). These results suggest that the chloroform- and hexane-soluble fraction mediated the mitogen-activated protein kinase (MAPK) inhibition, in particular the JNK pathway, thereby lowering the inflammatory cascades in LPS-activated murine microglia. Thus, our study suggests that the chloroform and hexane fractions of and their terpenoids may be potential drug candidates for drug discovery against LPS-induced neuroinflammation and neuroinflammatory-related neurodegeneration.
我们之前曾报道过，从 中提取的植物化学物质通过降低亚硝酸盐的产生和增加神经生长因子的产生来发挥抗炎和神经保护作用。然而，这些作用的具体机制尚未揭示。在本研究中，我们旨在探索 的抗炎机制及其植物化学物质。我们研究了 的各种溶剂级分，发现氯仿和正己烷亚级分在脂多糖 (LPS) 激活的小鼠小胶质细胞中显示出最显著的抗炎神经作用。同时，从氯仿和正己烷级分中分离出的萜类化合物表现出类似的抗炎神经作用，显著抑制 NO 和活性氧的产生，并降低诱导型一氧化氮合酶 (iNOS) 和环氧化酶的蛋白表达。有趣的是，这些萜类化合物抑制 c-Jun 末端激酶 (JNK) 的磷酸化，从而进一步抑制促炎介质的产生，包括前列腺素 E2、肿瘤坏死因子和白细胞介素 (IL-6 和 IL-1β)，其效力大于众所周知的 iNOS 抑制剂 NG-单甲基-L-精氨酸 (L-NMMA)。这些结果表明，氯仿和正己烷可溶级分介导了丝裂原激活蛋白激酶 (MAPK) 的抑制，特别是 JNK 途径，从而降低 LPS 激活的小鼠小胶质细胞中的炎症级联反应。因此，我们的研究表明， 和它们的萜类化合物的氯仿和正己烷级分可能是针对 LPS 诱导的神经炎症和神经炎症相关神经退行性变的药物发现的潜在候选药物。
