Diabetes mellitus causes abnormalities of angiogenesis leading to vascular dysfunction and serious pathologies. Diphlorethohydroxycarmalol (DPHC), which is isolated from Ishige okamurae, is well known for its bioactivities, including antihyperglycemic and protective functions against diabetes-related pathologies. In the present study, the inhibitory effect of DPHC on high glucose-induced angiogenesis was investigated on the human vascular endothelial cell line EA.hy926. DPHC inhibited the cell proliferation, cell migration, and tube formation in cells exposed to 30 mM of glucose to induce angiogenesis. Furthermore, the effect of DPHC against high glucose-induced angiogenesis was evaluated in zebrafish embryos. The treatment of embryos with DPHC suppressed high glucose-induced dilation in the retinal vessel diameter and vessel formation. Moreover, DPHC could inhibit high glucose-induced vascular endothelial growth factor receptor 2 (VEGFR-2) expression and its downstream signaling cascade. Overall, these findings suggest that DPHC is actively involved in the suppression of high glucose-induced angiogenesis. Hence, DPHC is a potential agent for the development of therapeutics against angiogenesis induced by diabetes.

Obesity is associated with several health complications and can lead to the development of metabolic syndrome. Some of its deleterious consequences are related to insulin resistance, which adversely affects blood glucose regulation. At present, there is a growing concern regarding healthy food consumption, owing to awareness about obesity. Seaweeds are well-known for their nutritional benefits. The brown alga Ishige okamurae (IO) has been studied as a dietary supplement and exhibits various biological activities in vitro and in vivo. The bioactive compounds isolated from IO extract are known to possess anti-obesity and anti-diabetic properties, elicited via the regulation of lipid metabolism and glucose homeostasis. This review focuses on IO extract and its bioactive compounds that exhibit therapeutic effects through several cellular mechanisms in obesity and diabetes. The information discussed in the present review may provide evidence to develop nutraceuticals from IO.

Among the components derived from brown algae, anionic sulfated polysaccharides, which contain sulfated fucose as the major monosaccharide, exert significant biological activities. In this study, we purified and structurally characterized sulfated polysaccharides from brown algae, Sargassum binderi (S. binderi; SBPs), and evaluated their biological activity in vitro and in vivo. The SBPs were separated based on their charges and their biophysical properties were investigated according to their functional groups, structural features, and molecular weights using FTIR, NMR, and MALS. Among all the SBPs, Fraction 4 (SBP-F4), with an average molecular weight of 2.867 × 105 g/mol, had the highest polysaccharide and sulfate contents (75.15 ± 0.25% and 24.08 ± 0.18%, respectively). The biological activities of SBP-F4 were investigated further in vitro and in vivo. Our results showed that SBP-F4 significantly suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in LPS-activated macrophages. Moreover, in the LPS-treated zebrafish model, a significant decrease in cell death and NO production was observed. Collectively, these results show that SBPs not only exert protective effects against LPS-induced cytotoxicity but also inhibit the activation and anti-inflammatory activity of macrophages. Therefore, polysaccharides derived from S. binderi are potential anti-inflammatory agents for use in clinical settings.

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.

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