title: The antiangiogenic activities of ethanolic crude extracts of four Salvia species.
abstract: Angiogenesis is one of cancer hallmarks that are required for both cancer progression and metastasis. In this study we examined the antiangiogenic properties of the ethanolic crude extracts of four Salvia species grown in Jordan.
  
  
  
  The direct antiangiogenic activity was evaluated using various models: ex vivo rat aortic ring assay, in vitro assessment of HUVEC proliferation and migration, and in vivo CAM assay, while we used the changes in the expression of HIF-1α and VEGF in breast cancer cells (MCF 7) as an indicative for the indirect antiangiogenic activity.
  
  
  
  All four crude extracts showed a potential antiangiogenic activity in the rat aortic assay, however two species were found to be cytotoxic against Fibroblast cell line (PLF); the finding that caused the exclusion of these two extracts from further studies. Of the two remaining extracts, S. triloba showed very promising direct and indirect antiangiogenic activities. S. triloba inhibited the HUVEC proliferation with an IC50 of 90 μg/mL and HUVEC migration by 82% at 150 μg/mL. Furthermore, the in vivo CAM assay also illustrated the high impact of S. triloba against the newly formed vessel in the chicken embryonic membrane. Interestingly, the S. triloba inhibited the expression of VEGF at the mRNA and protein and the HIF-1α mRNA in the MCF 7 breast cancer cells under both normoxic and hypoxic conditions.
  
  
  
  Taken together, all these findings of the direct and indirect angiogenic investigations nominated S. triloba as a highly potent antiangiogenic plant that may have chemotherapeutic and/or chemoprevention potentials.
authors: Department of Pharmacology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan. M.zihlif@ju.edu.jo.
authors: Malek
authors: M
authors: Zihlif
authors: Fatma
authors: F
authors: Afifi
authors: Rana
authors: R
authors: Abu-Dahab
authors: Amin Malik Shah
authors: AM
authors: Abdul Majid
authors: Hamzeh
authors: H
authors: Sumrein
authors: Mohanad M
authors: MM
authors: Saleh
authors: Zeyad D
authors: ZD
authors: Nassar
authors: Randa
authors: R
authors: Naffa
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D000431:Ethanol; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027544:Salvia / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D000431:Ethanol