Table 1.

Natural coumarins with antiangiogenic effects and their mechanisms.

Coumarin	Sources	Mechanism of Action	Concentrations	Reference
Galbanic acid	Ferula assafoetida	Decreases molecular angiogenesis pathways including VEGF, MAPK, JNK, and AKT	5, 10, 20, 40 µM for in vitro study and 0.1, 1 mg/Kg for Lewis lung cancer (LLC) mouse model, intraperitoneally (i.p.) injected once daily for 18 days	[126]
Umbelliprenin	Ferula species	Reduces and blocks angiogenesis marker activity including Ki-67, CD31, VEGF, MMP2, MMP9, and E-cadherin	3, 6.25, 12.5, 25, 50, 100, and 200 µg/mL	[127]
Murrangatin	Micromelum falcatum	Inhibition of phosphoinositol 3-kinase (PI3K)/AKT activity as angiogenic inducer	10, 50, 100 µM	[125]
Imperatorin	Angelica dahurica and Angelica archangelica	Blocks the expression of nuclear factor (NF-κB) target genes, such as MMP-9, VEGF, IL-6 that are induced by TNF-α	50, 100, 150 µM	[117]
Auraptene	Citrus sinensis	Inhibition of angiogenesis via suppression of MMP-2,9	12.5, 25, 50, 100 µM	[128]
Esculetin	Artemisia scoparia	Inhibition of angiogenesis via decreasing MMP expression and blocking phosphorylation of VEGFR-2, ERK1/2, Akt, and endothelial nitric oxide synthase (eNOS) induced by VEGF (20 ng/mL)	12.5, 25, 50 µg/ml	[31]
Osthol	Cnidium monnieri	Reduction of microvessel density (MVD) with blocked expression of VEGF and NF-κB	61, 122, and 244 mg/kg, i.p, once daily for two weeks in a mouse model of hepatocellular carcinoma (HCC)	[129]
Conferone	Ferula szwitsiana	Reduction of the production of the pro-angiogenic factors VEGF, Angiopoietin-1, and Angiopoietin -2	20 µM	[123]
Daphnetin	Changbai daphne	Inhibition of the expression of proteins involved in angiogenesis induced by VEGF such as MAPK, VEGFR2, ERK1/2, AKT, focal adhesion kinase (FAK), cSrc, and MMP and inhibition of NF-κB induced by TNF-α	37.5, 75, 150 µM	[124]
Scopolin	Erycibe obtusifolia Benth	Decreases VEGF, FGF-2 and IL-6 expressions	25, 50, 100 mg/kg, i.p, once daily for 10 days	[130]