Salwa Zekry Zekry

Natural products play a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of drugs and bioactive substances. Adding to the search for new sources of safe innovative antitumor drugs, here we reported a phytochemical study on Pulicaria undulata which revealed promising antiangiogenic agents. Six compounds were isolated and identified as xanthoxyline (1), stigmasterol (2), oleanolic acid (3), salvigenin (4), rhamnetin (5) and dihydroquercetin-4′-methyl ether (6) using nuclear magnetic resonance (NMR) spectroscopic techniques. Compound 3 and 4 are first reported in Pulicaria genus. Both the extract and isolated compounds were evaluated for in vitro antiproliferative activity against breast cancer cell line (MCF-7). In vivo antiproliferative activity against Ehrlich’s ascites carcinoma (EAC) were also assessed. The P. undulata extract and isolates showed significant reduction in tumor weight, decreased both serum vascular endothelial growth factor B (VEGF-B) levels and vascular endothelial growth factor receptor 2 (VEGFR-2) expression significantly compared to the control EAC group, suggesting an antiangiogenic activity through the inhibition of VEGF signaling. Besides, they displayed reduction in CD34 expression, confirming their antiangiogenic effect. Moreover, the potential affinity of isolated compounds to human estrogen nuclear receptor-alpha (hER-α), the most recognized modulator of VEGFR-2 expression, was virtually estimated through molecular modeling studies. The most promising activity profiles were assigned to the investigated flavonoids, compounds 4–6, as well as the alkyl-phenylketone, compound 1. Additionally, these four top active compounds showed respective high to intermediate docking scores while possessing preferential binding with hER-α critical pocket residues. Based on the provided data, these isolated compounds illustrated promising inhibitors of VEGF-stimulated angiogenesis, which could be a possible mechanism for their anticancer activity.

Medicinal plants are a prominent source of secondary metabolites and bioactive innovative molecules with interesting and remarkable biological activities. The Sinai Peninsula is considered an exceptional reservoir of many indigenous medicinal plants that have been used for treatment of many ailments; Pulicaria is a promising medicinal genus and one of the widest spread desert plants growing wild in Egypt. Some plants within the genus are used as traditional herbal medicines. Pulicaria is a well-known natural source of several bioactive compounds and used in traditional medicine in the many countries. Most importantly, previous studies of Pulicaria species allowed the isolation of various compounds such as flavonoids and terpenes. Our review tends to support the therapeutic value of this genus. Many recent studies suggested that most of the reported biological activities of Pulicaria are due to its high content of polyphenols, particularly flavonoids. This review highlights the phytochemical constituents of this important and valuable genus as well as its different reported biological activities.