Fucoidan from Undaria pinnatifida prevents vascular dysfunction through PI3K/Akt/eNOS-dependent mechanisms in the l-NAME-induced hypertensive rat model

Abstract

Despite major scientific advances in its prevention, treatment and care, hypertension remains a serious condition that might lead to long-term complications such as heart disease and stroke. The great majority of forms of hypertension eventually result from an increased vasomotor tone activity that is regulated by endothelial NOS (eNOS) in vascular endothelium. Here, we examined the effect of fucoidan on eNOS activation in human umbilical vein endothelial cells (HUVECs). We also examined the effects of functional components of Undaria pinnatifida fucoidan on blood pressure and vascular function in eNOS inhibition-induced hypertensive rats in vivo. Our results suggest that fucoidan increased nitric oxide production by activating eNOS and Akt phosphorylation, which could be impaired by Akt or eNOS inhibitors. In the hypertensive rat model, treatment of fucoidan resulted in potent and persistent reduction of high blood pressure (BP) even after drug withdrawal. Our results showed that the mechanisms might involve protection against vascular structure damage, enhanced endothelium-independent vascular function and inhibition of abnormal proliferation of smooth muscle cells, which are mediated by the Akt-eNOS signaling pathway. Moreover, fucoidan treatment reduced the vascular inflammation and oxidative stress control caused by iNOS expression. Together, these results support a putative role of fucoidan in hypertension prevention and treatment.

Fucoidan Isolated from Saccharina japonica Inhibits LPS-Induced Inflammation in Macrophages via Blocking NF-κB, MAPK and JAK-STAT Pathways

“…Nitric oxide, an important pro-inflammatory mediator, is mainly synthesized by iNOS enzyme which would excessive express in reaction to various immune and inflammatory stimuli. The excessively produced NO could result in the generation of various pro-inflammatory mediators and cytokines, which would further promote the development of inflammation and finally relate to tissue damage and detrimental inflammatory disorders [40]. The high level of iNOS is often accompanied with over-expressed COX-2 in the inflammatory process, and COX-2 is the key enzyme required for the conversion of arachidonic acid into PGE2 which is a characteristic marker of inflammatory damage [7].…”

Algal Polysaccharides as Therapeutic Agents for Atherosclerosis

“…In a different study, NG-nitro-L-arginine methyl ester (L-NAME) was used to induce hypertension in mice. Oral administration of 100 mg/kg/day of fucoidan for 4 weeks in these animals decreased blood pressure and increased production of nitric oxide production ( 31 ). Notably, many of these in vivo studies were done in male rats and mice only and further research is needed to evaluate their efficacy in female animals.…”

Research Progress on Signaling Pathway‐Associated Oxidative Stress in Endothelial Cells

“…AKT also plays a critical role in the control of phosphorylation of eNOS-ser1177 in vivo. Li et al [39] revealed that the upregulation of phosphorylated AKT and eNOS induced by fucoidan was counteracted by the suppression of AKT and eNOS phosphorylation protein expression. PI3K and AKT are downstream effectors of insulin signaling and are important signaling molecules in the regulation of glycogen metabolism in myocytes, lipocytes, and hepatocytes.…”