Open Access Open Badges Research article

The antiangiogenic activities of ethanolic crude extracts of four Salvia species

Malek Zihlif1*, Fatma Afifi2, Rana Abu-Dahab2, Amin Malik Shah Abdul Majid3*, Hamza Somrain1, Mohanad M Saleh1, Zeyad D Nassar34 and Randa Naffa5

Author Affiliations

1 Department of Pharmacology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan

2 Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan Amman, Jordan

3 Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia

4 University of Queensland, School of Pharmacy, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia

5 Department of Physiology and Biochemistry, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan

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BMC Complementary and Alternative Medicine 2013, 13:358  doi:10.1186/1472-6882-13-358

Published: 13 December 2013



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.

Salvia triloba; Salvia hormium; Salvia dominica; Salvia syriaca; Antiangiogenesis; MCF 7; Jordan