Metabolomics and molecular networking studies to uncover the chemodiversity of three <i>Pulicaria</i> species in Qatar and their correlation with antioxidant and anticancer potential

Qatari <i>Pulicaria</i> species-<i>Pulicaria undulata</i> (L.) C. A. Mey., <i>Pulicaria sicula</i> (L.) Moris and <i>Pulicaria gnaphalodes</i> (Vent.) Boiss have been a source of food and medicine among locals. However, these species have taxonomic issues and alternative uses. Hence, this study aimed to comparatively investigate the chemical diversity of three Qatari <i>Pulicaria</i> species, including their antioxidant and anticancer potential. HPLC-QTOF-MS-based untargeted metabolomics and molecular networking approaches were used to study the chemical diversity. The total phenolic and flavonoid contents, including antioxidant activity, were determined using standard colorimetric microplate-based assays. The anticancer activity was evaluated in human breast cancer MDA-MB-231 cells using the MTT assay. The methanolic extracts of three <i>Pulicaria</i> species had distinct chemical signatures, with a notable portion of similar compounds. Phytochemically, <i>P. undulata</i> and <i>P. sicula</i> were more similar to each other than <i>P. gnaphalodes</i>. Among the 36 compounds identified across all extracts, sesquiterpene lactones represented the most abundant chemical class. Interestingly, the methanolic extract of <i>P. undulata</i> was particularly qualitatively rich in sesquiterpene lactones, whereas <i>P. sicula</i> was comparatively richer in flavonoids, quantitatively. The observed antioxidant activity in <i>P. sicula</i> and <i>P. undulata</i> was nearly identical, despite <i>P. sicula</i> having significantly higher contents of total phenolics and flavonoids. The anticancer activity of extracts from all three species was dose-dependent, with <i>P. undulata</i> exhibiting the highest potency among them. This study provides valuable insights into the comparative chemodiversity and bioactivity profiles of three <i>Pulicaria</i> species, crucial for their quality control, and precise and sustainable use as anticancer or nutraceutical agents.