1. Physalins from Witheringia solanacea as modulators of the NF-kappaB cascade.
- Author
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Jacobo-Herrera NJ, Bremner P, Marquez N, Gupta MP, Gibbons S, Muñoz E, and Heinrich M
- Subjects
- Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, HeLa Cells drug effects, Humans, Interleukin-6 genetics, Jurkat Cells drug effects, Lactones chemistry, Lactones pharmacology, Luciferases genetics, Luciferases metabolism, Molecular Structure, NF-kappa B metabolism, Panama, Plant Leaves chemistry, Secosteroids, Steroids chemistry, Steroids pharmacology, Tetradecanoylphorbol Acetate pharmacology, Tumor Necrosis Factor-alpha pharmacology, Anti-Inflammatory Agents isolation & purification, Lactones isolation & purification, NF-kappa B antagonists & inhibitors, Plants, Medicinal chemistry, Solanaceae chemistry, Steroids isolation & purification
- Abstract
Crude extracts of Witheringia solanacea leaves showed inhibition of NF-kappaB activation at 100 microg/mL induced by phorbol 12-myristate-13-acetate (PMA) in HeLa cells stably transfected with a luciferase reporter gene controlled by the IL-6 promoter. Three physalins were isolated from an active fraction, namely, physalins B (1), F (2), and D (3). Of these compounds, 1 and 2 demonstrated inhibitory activities on PMA-induced NF-kappaB activation at 16 and 8 microM and induced apoptosis after 24 h in a cell-cycle analysis using a human T cell leukemia Jurkat cell line. Compound 2 also inhibited TNF-alpha-induced NF-kappaB activation at 5 microM through the canonical pathway, but was inactive in the Tet-On-Luc assay, indicating specificity of action, although it interfered with Tet-On-Luc at higher concentrations. It is suggested that the presence of a double bond and an epoxy ring between carbons 5 and 6 in compounds 1 and 2, respectively (which are not present in compound 3), are related to their anti-inflammatory activity.
- Published
- 2006
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