Physalins from Witheringia solanacea as modulators of the NF-κB cascade

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Jacobo-Herrera, NJ, Bremner, P, Márquez, N, Gupta, MP, Gibbons, S, Muñoz, E & Heinrich, M 2006, 'Physalins from Witheringia solanacea as modulators of the NF-κB cascade', Journal of Natural Products, vol. 69, no. 3, pp. 328-331.

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Crude extracts of Witheringia solanacea leaves showed inhibition of NF-?B activation at 100 µg/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-?B activation at 16 and 8 µM 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-a-induced NF-?B activation at 5 µM 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.

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