ABSTRACT
Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1) with IC50 value of 2.43 µg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3) with IC50 value of 1.38 µg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1) and nortrachelogenin 4-O-ß-D-glucopyranoside (2), together with six known compounds. The lignan compounds 1-4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 µM and 9.46 µM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 µM, 6.47 µM and 2.92 µM, respectively.
Subject(s)
Plant Extracts/pharmacology , Signal Transduction/drug effects , Tracheophyta/chemistry , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Interferon-gamma/metabolism , Interleukin-6/metabolism , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Plant Extracts/chemistry , STAT1 Transcription Factor/metabolism , STAT3 Transcription Factor/metabolismABSTRACT
Nineteen secolignans (1-19), including five new ones (1-5), were isolated from the whole plant of Peperomia dindygulensis. Their structures including stereochemistry were determined by spectroscopic methods, in particular NMR and electronic CD (ECD) analysis. All the isolates were evaluated for their inhibitory activities against IFN-γ/STAT1 as well as IL-6/STAT3 signaling pathway by the method of Luciferase assay. Six 2-methene type secolignans (1, 2, 6-9) exhibited significant inhibitory activities against JAK-STAT pathways with the IC50 values both lower than 10µM.