Angiogenic effect of the aqueous extract of Cynodon dactylon on human umbilical vein endothelial cells and granulation tissue in rat

Abstract

BackgroundCynodon dactylon, a valuable medicinal plant, is widely used in Iranian folk medicine for the treatment of various cardiovascular diseases such as heart failure and atherosclerosis. Moreover, its anti-diabetic, anti-cancer and anti-microbial properties have been also reported. Concerning the critical role of angiogenesis in the incidence and progression of tumors and also its protective role in cardiovascular diseases, we investigated the effects of the aqueous extract prepared from the rhizomes of C. dactylon on vascular endothelial growth factor (VEGF) expressions in Human Umbilical Vein Endothelial Cells (HUVECs) and also on angiogenesis in carrageenan induced air-pouch model in rats.MethodsIn the air-pouch model, carrageenan was injected into an air-pouch on the back of the rats and following an IV injection of carmine red dye on day 6, granulation tissue was processed for the assessment of the dye content. Furthermore, in an in vitro study, angiogenic property of the extract was assessed through its effect on VEGF expression in HUVECs.ResultsOral administration of 400 mg/kg/day of the extract significantly increased angiogenesis (p < 0.05) and markedly decreased neutrophil (p < 0.05) and total leukocyte infiltration (p < 0.001) into the granulation tissues. Moreover, the extract increased the expression of total VEGF in HUVECs at a concentration of (100 μl/ml).ConclusionThe present study showed that the aqueous extract of C. dactylon promotes angiogenesis probably through stimulating VEGF expression.

Antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells

“…The widely prescribed, AMPK-activating antidiabetic drug metformin has been shown to inhibit angiogenesis in vitro and in vivo (55) and currently is being evaluated in several clinical trials for various types of cancer (56). However, the concentrations of metformin required to activate AMPK in HUVEC are at least 1,000 times higher than those required of itraconazole (in the range of low millimoles) (55), suggesting that itraconazole might be significantly more effective than metformin at inhibiting angiogenesis in patients. Another drug in trials for cancer, the natural product curcumin, also has been shown to activate AMPK and inhibit mTOR (57)(58)(59).…”

A Metabolic Inhibitory Cocktail for Grave Cancers: Metformin, Pioglitazone and Lithium Combination in Treatment of Pancreatic Cancer and Glioblastoma Multiforme

“…Metformin (orally, 50 mg/kg) significantly (p \ 0.01) decreased vascularization in granulomatous tissue by 34 % in rats (Soraya et al 2012). Metformin at levels between 0.5 and 3 mM significantly (p \ 0.001) reduced VEGF mRNA expression and endothelial cell migration (Soraya et al 2012).…”

“…Metformin activities were studied on migration of human umbilical vein endothelial cells, on VEGF levels and on angiogenesis in the rat air pouch model (Soraya et al 2012). Metformin (orally, 50 mg/kg) significantly (p \ 0.01) decreased vascularization in granulomatous tissue by 34 % in rats (Soraya et al 2012).…”

Chemical constituents and pharmacological effects of Cynodon dactylon- A Review

“…Moreover, the extract increased the expression of total VEGF in HUVECs at a concentration of (100 μl/ml). Accordingly, the aqueous extract of Cynodon dactylon promotes angiogenesis probably through stimulating VEGF expression [105]. The ethanol extract of aerial parts of Cynodon dactylon significant reduced the number of writhes and stretches induced in mice by 1.2% acetic acid solution.…”