莪术倍半萜和二萜类化合物对 STAT3 的抑制活性。

STAT3-inhibitory activity of sesquiterpenoids and diterpenoids from Curcuma phaeocaulis.

机构信息

Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, 181 Ipsin-gil, Jeongeup-si, Jeonbuk 56212, Republic of Korea.

出版信息

Bioorg Chem. 2019 Dec;93:103267. doi: 10.1016/j.bioorg.2019.103267. Epub 2019 Sep 10.

DOI:10.1016/j.bioorg.2019.103267

PMID:31586702

Abstract

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 IC 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.

摘要

从姜黄中分离得到了三种新的倍半萜类化合物（化合物 4、5 和 26），以及 23 种已知的倍半萜类化合物（化合物 1-3 和 6-25）和两种二萜类化合物（化合物 27 和 28），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，并与以前的研究数据进行了比较。所有分离物均通过荧光素酶报告基因测定法测试了对白细胞介素（IL）-6 刺激的 STAT3 表达的抑制活性，其中 curzerenone（21）和 8-表-高半乳糖内酯（28）显示出有希望的信号转导和转录激活因子（STAT3）抑制活性，IC 值分别为 4.8 和 4.1 μM。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，显著抑制了促炎基因 IL-1β 和 C 反应蛋白（CRP）的 mRNA 表达水平。这些结果表明，curzerenone（21）和 8-表-高半乳糖内酯（28）可能是改善严重炎症性疾病的潜在候选药物。