Title
STAT3-inhibitory activity of sesquiterpenoids and diterpenoids from Curcuma phaeocaulis
Author
Hyun-Jae Jang, Hyung-Jin Lim, Eun-Jae Park, Seung-Jae Lee, Soyoung Lee, Seung Woong Lee, Mun-Chual Rho
Year
2019
Journal
Bioorganic Chemistry
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 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.
Instrument
J-710
Keywords
Circular dichroism, Absolute configuration, Stereochemistry, Materials, Biochemistry