STAT3-inhibitory activity of sesquiterpenoids and diterpenoids from Curcuma phaeocaulis

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.