Jacobo-Herrera, Nadia Judith;
(2005)
Anti-inflammatory properties and bioactive natural products from Witheringia solanacea, Withania frutescens (Solanaceae), and Veleriana officinalis (Valerianaceae) using NF-kappaB as a molecular target.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Nuclear Factor kappaB (NF-kB) is a transcription factor implicated in the regulation of many pro-inflammatory cytokines and related proteins that participate in a number of inflammatory diseases. The inhibitory activity of NF-kB cascade was evaluated through bioassay-guided fractionation for three medicinal plants, Witheringia solanacea, Withania frutescem, and Valeriana officinalis. The selected plants are included in an Anti-Inflammatory Natural Products (AINP) EU-funded project, which attempts to identify new natural products as inhibitors of NF-kB activation. Six different chromatography techniques were employed in the fractionation of crude extracts and isolation of pure compounds and the latter were subsequently characterised using spectroscopic techniques (NMR and MS experiments). Luciferase-based assays were performed to test the biological activity of fractions and compounds using HeLa cells. These cells were stably transfected with a luciferase reporter gene controlled by the IL-6 promoter (one of the target genes that promotes NF-KB activation), and phorbol 12-myristate-13-acetate was used as a stimulant of NF-KB at 50 ng/ml for 7 h. Three compounds were isolated from an active fraction of Witheringia solanacea, which were identified as physalins B, F and D. Physalins B and F inhibited NF-KB at 16 and 8 μM, whereas physalin D was inactive. Subsequent cell cycle assays performed for physalins F and B revealed that both induce apoptosis after 24 h at 10 and 20 μM, respectively. Two compounds were isolated from the chloroform extract of Withania frutescens, 5,6-epoxy-1- oxowitha-2, 14, 24-trienolide and withaferin A, though the latter was recovered together with an unidentified compound. 5,6-epoxy-l-oxowitha-2,14,24-trienolide reduced NF-kB activity at 25 μM, whereas the fraction containing withaferin A reduced NF-kB activity at 25 μg/ml. The EtOAc extract of Valeriana officinalis also inhibited the NF-kB cascade at 100 μg/ml, though, of its three compounds isolated, only one, acetylvalerenolic acid, showed inhibitory activity at 100 μg/ml. This study provides molecular evidence for the anti-inflammatory activity of these plants, and some of their compounds isolated as small molecule inhibitors of the NF-kB pathway.
Type: | Thesis (Doctoral) |
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Qualification: | Ph.D |
Title: | Anti-inflammatory properties and bioactive natural products from Witheringia solanacea, Withania frutescens (Solanaceae), and Veleriana officinalis (Valerianaceae) using NF-kappaB as a molecular target |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Thesis digitised by ProQuest |
URI: | https://discovery.ucl.ac.uk/id/eprint/10116670 |
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