Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacognosy

Succulents are mostly desert plants and considered as promising sources for the discovery of unique metabolites with a diverse range of bioactivities.Thus, in this study six succulents, namely, Aptenia cordifolia var. variegata (L.f.), Glottiphyllum linguiforme (L.), Carpobrotus edulis (L.), family Aizoaceae; and Ferocactus glaucescens (DC.), F. pottsii (Salm-Dyck), F. herrerae, family Cactaceae, were subjected to genomic analysis through start codon-targeted (SCoT) marker technique and metabolic profiling using LC{u2010}HR{u2010}ESI{u2010}MS to help in their identification and authentication. Multivariate analyses of the mass data and molecular data revealed that the chemical characters of the six species were able to generate almost the same phylogenetic relationships with high degree of consistence. The chemopreventive potential of the ethanolic extracts of the six species was investigated using NQO1 induction bioassay in cultured murine hepatoma cells (Hepa 1c1c7) and nitric oxide (NO) inhibition in (LPS)-induced RAW 264.7 macrophage cells at 100 æg/mL. A. cordifolia var. variegata, C. edulis, F. glaucescens and F. herrerae showed marked NQO1 inducing activity. All extracts did not show remarkable effects in the NO inhibition bioassay except for F. glaucescens extract. Through the dereplication approach using metabolomics (LC/MS-PCA, HCA, OPLS-DA), and bioassay screening, the most promising species, A. cordifolia var. variegata and F. glaucescens,were selected for further phytochemical investigations; resulting in the isolation of 12 compounds from A. cordifolia var. variegata and 6 compounds from F. glaucescens. All isolated compounds were tested for their potential chemopreventive activities through either the inhibition of NO or the induction of NQO1 enzyme activity and the results were further confirmed by western blots of iNOS and NQO1 protein expressions, respectively

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