Physalins from Witheringia solanacea as modulators of the NF-kappaB cascade.
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.
Jacobo-Herrera
Nadia J
NJ
Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, University of London, UK.
Bremner
Paul
P
Marquez
Nieves
N
Gupta
Mahabir P
MP
Gibbons
Simon
S
Muñoz
Eduardo
E
Heinrich
Michael
M
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D019169:Jurkat Cells / Q000187:drug effects; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010176:Panama; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012632:Secosteroids; D019657:Solanaceae / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D007783:Lactones; D016328:NF-kappa B; D012632:Secosteroids; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; C441429:physalin D; C033270:physalin B; C075425:physalin F; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate