Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2019-09-10 , DOI: 10.1016/j.bioorg.2019.103267 Hyun-Jae Jang 1 , Hyung-Jin Lim 1 , Eun-Jae Park 1 , Seung-Jae Lee 1 , Soyoung Lee 1 , Seung Woong Lee 1 , Mun-Chual Rho 1
Three new sesquiterpenoids (compounds 4, 5, and 26), along with 23 known sesquiterpenoids (compounds 1–3 and 6–25) and two diterpenoids (compounds 27 and 28), were obtained from Curcuma phaeocaulis, and their chemical structures were determined through nuclear magnetic resonance (NMR), circular dichroism (CD), and high-resolution electrospray ionization (HRESIMS) spectroscopic data, which were compared to the data from previous studies. All isolates were tested for inhibitory activity against interleukin (IL)-6-stimulated STAT3 expression using a luciferase reporter assay, and curzerenone (21) and 8-epi-galanolactone (28) displayed promising signal transducer and activator of transcription (STAT3)-inhibitory activities with IC50 values of 4.8 and 4.1 μM, respectively. In addition, these candidates significantly suppressed the mRNA expression levels of the proinflammatory genes IL-1β and C-reactive protein (CRP) via blockade of the IL-6-activated Janus kinase 2 (JAK2)/STAT3 and ERK-MAPK signaling pathways. These results suggest that curzerenone (21) and 8-epi-galanolactone (28) may be potential candidates for ameliorating severe inflammatory diseases.
中文翻译:
姜黄中倍半萜和二萜的STAT3抑制活性。
三个新的倍半萜类化合物(化合物4,5,和26)中,用23倍半萜已知(化合物一起1 - 3和6 - 25)和两个二萜类化合物(化合物27和28)中,从得到的莪,并通过核磁共振(NMR),圆二色性(CD)和高分辨率电喷雾电离(HRESIMS)光谱数据确定了它们的化学结构,并将这些数据与以前的研究进行了比较。使用萤光素酶报告基因检测法测试了所有分离株对白介素(IL)-6刺激的STAT3表达的抑制活性,姜黄酮(21)和8-表-半乳糖内酯(28)显示出有希望的信号转导子和转录激活子(STAT3)- IC 50的抑制活性分别为4.8和4.1μM。此外,这些候选物通过阻断IL-6激活的Janus激酶2(JAK2)/ STAT3和ERK-MAPK信号通路,显着抑制了促炎基因IL-1β和C反应蛋白(CRP)的mRNA表达水平。这些结果表明,姜黄酮(21)和8-表-半乳糖内酯(28)可能是减轻严重炎症性疾病的潜在候选药物。