Inhibition of Angiogenesis: A Novel Effect of Zataria Multiflora


Background: Angiogenesis, the formation of new blood vessels from preexisting ones, is among the most important physiological and pathological processes that occur in the body. Under pathological conditions such as tumor growth, psoriasis, corneal neovascularization and rheumatoid arthritis, angiogenesis is substantial for the development of the disease. Zataria multiflora is a member of the Labiatae family with a vast range of traditional uses which has been long known and applied in Iran old medicine. The aim of this study was the evaluation of anti-angiogenic potential of Zataria multiflora.
Materials and Methods: In this study, human umbilical vein endothelial cells (HUVECs) were isolated from newborn umbilical veins and then cultured for cytotoxicity (LDH test) assay. Regarding LDH results, following tests such as angiogenesis (cytodex-3 micro carrier) and migration (wound healing) tests were designed.
Results: The cytotoxicity assays showed no toxicity of Z.multiflora toward HUVECs in the range of 10-450µg/mL of the extract. This extract was also able to inhibit angiogenesis and migration at 200µg/mL.
Conclusions: Our data clearly demonstrated an inhibitory effect of Z.multiflora on angiogenesis and migration of HUVECs. Z.multiflora could be introduced as a significant angiogenesis inhibitor for angiogenesis-dependent diseases in further complementary studies.



Mostafaie A, Mohammadi-Motlagh HR, Mansouri K. Angiogenesis and the models to study angiogenesis Yakhteh Med J. 2010;11:374-381.

Norooznezhad AH, Norooznezhad F. How Could Cannabinoids Be Effective in Multiple Evanescent White Dot Syndrome? A Hypothesis. J Rep Pharm Sci. 2016;5: 49-52.

Shakiba Y, Mansouri K, Arshadi D, et al. Corneal neovascularization: molecular events and therapeutic options. Recent Pat Inflamm Allergy Drug Discov. 2009;3(3):221-231.

Heidenreich R, Röcken M, Ghoreschi K. Angiogenesis: the new potential target for treatment of psoriasis? Drug News Perspect. 2008;21(2):97-105.

Szekanecz Z, Koch AE. Angiogenesis and its targeting in rheumatoid arthritis. Vascul Pharmacol. 2009;51(1):1-7.

Nguyen A, Hoang V, Laquer V, et al. Angiogenesis in cutaneous disease:Part I. J Am Acad Dermatol.2009;61(6):921-942.

Plank MJ, Sleeman BD. Tumor–induced angiogenesis: A review. J Theor Med. 2004;5(3-4):137-153.

Kuwano M, Fukushi J, Okamoto M, et al. Angiogenesis factors. Intern Med. 2001;40(7):565-572.

Bischoff J, Griffioen AW. In memoriam Dr. Judah Folkman. Angiogenesis. 2008;11(1):1-2.

Zargari A. Medicinal Plants. Tehran:Tehran University Press. 1990;1–57.

Jafari S, Amanlou M, Borhan-Mojabi K, et al. Comparative study of Zataria multiflora and Anthemis nobelis extracts with Myrthus communis preparation in the treatment of recurrent aphthous stomatitis. Daru. 2003;11(1):23–27.

Jaffary F, Ghannadi A, Siahpoush A. Antinociceptive effects of hydroalcoholic extract and essential oil of Zataria multiflora. Fitoterapia. 2004;75(2):217–220.

Hosseinzadeh H, Ramezani M, Salmani GA. Antinociceptive, anti inflammatory and acute toxicity effects of Zataria multiflora Boiss extracts in mice and rats. J Ethnopharmacol. 2000;73(3):379–385.

Sharififar F, Moshafi MH, Mansouri SH, et al. In vitro evaluation of antibacterial and antioxidant activities of the essential oil and methanol extract of endemic Zataria multiflora Boiss. Food Control.2007;18: 800–805.

Bidmeshkipour A, Shirvani Farsani Z, et al. Isolation of human umbilical vein endothelial cells using kiwifruit actinidin. Yakhteh Med J. 2007;9(2):151-156.

Spiridonov NA, Konovalov DA, Arkhipov VV. Cytotoxicity of some Russian ethno medicinal plants and plant compounds. Phytother Res. 2005;19(5):428-432.

Auerbach R, Lewis R, Shinners B, et al. Angiogenesis assays: a critical overview.Clin Chem. 2003;49(1):32-40.

Nehls V, Drenckhahn DA. A novel,microcarrier-based in vitro assay for rapid and reliable quantification of three-dimensional cell migration and angiogenesis. Microvasc Res. 1995;50(3):311-22.

Mansouri K, Mostafie A, Rezazadeh D,et al. New function of TSGA10 gene in angiogenesis and tumor metastasis: a response to a challengeable paradox. Hum Mol Genet. 2016;25(2):233-244.

Norooznezhad AH, Norooznezhad F, Ahmadi K. Next target of tranilast: inhibition of corneal neovascularization. Med Hypotheses. 2014;82(6):700-2.

Sauder DN, Dekoven J, Champagne P, et al. Neovastat [AE-941], an inhibitor of angiogenesis: Randomized phase I/II clinical trial results in patients with plaque psoriasis. J Am Acad Dermatol. 2002;47(4):535–41.

Shakiba Y, Mansouri K, Mostafaie A. Anti-angiogenic effect of soybean kunitz trypsin inhibitor on human umbilical vein endothelial cells. Fitoterapia. 2007;78(7-8): 587–9.

Hassan ZM, Feyzi R, Sheikhian A, et al. Low molecular weight fraction of shark cartilage can modulate immune responses and abolish angiogenesis. Int Immunopharmacol. 2005;5(6):961–970.

Mohammadi Motlagh HR, Mansouri K, Shakiba Y, et al. Anti-angiogenic effect of aqueous extract of shallot [Allium ascalonicum] bulbs in rat aorta ring model. Yakhteh Med J. 2009;11(2):190-195.

Keshavarz M, Bidmeshkipoor A, Mostafaie A, et al. Anti tumor activity of Salvia officinalis is due to its anti-angiogenic, anti-migratory and anti-proliferative effects. Cell J (Yakhteh).2011;12(4):477-482.

Mostafaie A, Mansouri K, Norooznezhad A, et al. Anti-angiogenic activity of ficus carica latex extract on human umbilical vein endothelial cells. Cell J (Yakhteh). 2011;12(4):525-528.

Keshavarz M, Norooznezhad AH, Mansouri K, et al. Cannabinoid (JWH-133) therapy could be effective for treatment of corneal neovascularization. Irn J Med Hypotheses Ideas. 2010; 4: 3.

Mansouri K, Mahamed-Khosroushahi L, Rasouli H. Anti-angiogenic/inflammatory behavior of mushroom ganoderma lucidum extract could be effective for treatment of corneal neovascularization: A hypothesis. J Rep Pharm Sci. 2014;3: 14-18.

- Arshadi D, Mansouri K, Khodarahmi R, et al. In vitro anti-angiogenic activity of Persian Shallot (Allium Hirtifolium) extract is mediated through inhibition of endothelial cell proliferation/migration and down-regulation of VEGF and MMP expression. J Rep Pharm Sci. 2014;3(1):65-79.

IssueVol 11, No 2 (2017) QRcode
Angiogenesis Zatariamultiflora Endothelialcells Cell migration

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Norooznezhad AH, Keshavarz M, Norooznezhad F, Mansouri K. Inhibition of Angiogenesis: A Novel Effect of Zataria Multiflora. Int J Hematol Oncol Stem Cell Res. 2017;11(2):96-101.