Ishige okamurae Extract and Its Constituent Ishophloroglucin A Attenuated In Vitro and In Vivo High Glucose-Induced Angiogenesis.

K.H.N Fernando,Bomi Ryu,Yunfei Jiang,You-Jin Jeon,Hye-Won Yang

doi:10.3390/ijms20225542

Abstract

Diabetes is associated with vascular complications, such as impaired wound healing and accelerated vascular growth. The different clinical manifestations, such as retinopathy and nephropathy, reveal the severity of enhanced vascular growth known as angiogenesis. This study was performed to evaluate the effects of an extract of Ishige okamurae (IO) and its constituent, Ishophloroglucin A (IPA) on high glucose-induced angiogenesis. A transgenic zebrafish (flk:EGFP) embryo model was used to evaluate vessel growth. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), gap closure, transwell, and Matrigel® assays were used to analyze the proliferation, migration, and capillary formation of EA.hy926 cells. Moreover, protein expression were determined using western blotting. IO extract and IPA suppressed vessel formation in the transgenic zebrafish (flk:EGFP) embryo. IPA attenuated cell proliferation, cell migration, and capillary-like structure formation in high glucose-treated human vascular endothelial cells. Further, IPA down regulated the expression of high glucose-induced vascular endothelial growth factor receptor 2 (VEGFR-2) and downstream signaling molecule cascade. Overall, the IO extract and IPA exhibited anti-angiogenic effects against high glucose-induced angiogenesis, suggesting their potential for use as therapeutic agents in diabetes-related angiogenesis.

Highlights

Diabetes is associated with secondary metabolic complications, such as insulin resistance and hyperinsulinemia, leading to abnormal angiogenesis [1]
The results were 117.12%, 102.95%, 97.80%, and 92.21% when treated with Ishophloroglucin A (IPA) at concentrations of 0.05, 0.15, 0.5, and 1.5 μM, respectively. These results suggest that IPA exerts anti-angiogenic effects by inhibiting high glucose-induced vascular cell proliferation
The findings of the present study demonstrated the anti-angiogenic effects of Ishige okamurae (IO) from a marine source

Summary

Introduction

Diabetes is associated with secondary metabolic complications, such as insulin resistance and hyperinsulinemia, leading to abnormal angiogenesis [1]. Development of new microvessels from the existing vessels is known as angiogenesis [2]. Diabetes is characterized by inadequate angiogenesis in some organs and excessive angiogenesis in some others [3]. Apart from its role in several pathological conditions, angiogenesis plays a crucial role in normal growth and development [4]. Excessive angiogenesis causes the degradation of vascular endothelial cells from the extracellular matrix, enhancement of cell proliferation, migration, and formation of extravascular networks [5]. Excessive angiogenesis is observed in diabetic retinopathy and nephropathy, resulting in the loss of vision and renal failure, respectively [6]

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Results

Conclusion