# Therapeutic Potential of Seaweed-Derived Bioactive Compounds for Cardiovascular Disease Treatment
## 2 Seaweed-Derived Phlorotannins with Therapeutic Potential against CVD
used the EA.hy926 cells and zebrafish model to systematically establish the potential mechanisms of the vasodilation produced by diekol and diphlorothohydroycarmalol isolated from _Ecklonia cava_ (_E. cava_) and _Ishige okamurae_ (I. okamurae) [35; 36] (Table 1). In addition, four major phlorotannins--dieckol, 2,7-phloroglucinol-6,6-bieckol, phlorofucofuroeckol A, and pyrogallol-phloroglucinol-6,6-bieckol--isolated from _Ecklonia cava_ effectively inhibited monocyte-associated vascular inflammation and dysfunction by suppressing monocyte migration and protecting monocyte-associated endothelial cell death [37]. Moreover, pyrogallol-phloroglucinol-6,6\({}^{\prime}\)-bieckol and dieckol isolated from _E. cava_ have been shown to improve blood circulation in mice fed diets to induce obesity and hypertension [36; 38]. Therefore, while numerous factors contribute to hypertension, it is well recognized that an increased vascular tone is always the ultimate goal. The evidence mentioned above has great pharmaceutical potential, with some already being used in the clinical trial phase. Clinical studies have shown cardiovascular protection, supporting the benefits of polyphenols extracted from land plants [39]. Nevertheless, only a few epidemiological studies have discussed the association between the consumption of specific components of seaweed and blood pressure. Despite investigating the benefits of single compounds from seaweed, the general components, including minerals, fiber, and peptides, were more popular in clinical trials. This might be because high doses of these compounds have comparatively low side effects. A case control study demonstrated the anti-hypertensive effect of _Undaria pinnatifida_ powder (5 g/capsule/day) by significantly reducing blood pressure in elderly Japanese patients following 8 weeks of administration [40]. However, [PERSON] et al. reported that no reduction in blood pressure occurred in healthy adults who were administered the _Fucus vesicusus_ extract [41]. As mentioned above, several phlorotannins have been confirmed to possess effects against hypertension by ACE inhibition, calcium regulation, antagonism of L-type calcium channels, or activation of the critical pathway (PI3K/Akt/eNOS). Despite these mechanisms being verified, many other physiological signaling pathways in vascular regulation remain unclear. It will be helpful to explore the cardiovascular protection or anti-hypertension properties of phlorotannin via its use as a potassium channel opener and angiotensin receptor blocker. Diabetes mellitus (DM) is a prime risk factor for dramatically increasing CVD, contributing to more than 3 million cardiovascular deaths worldwide each year [42]. Type 2 diabetes mellitus (T2 DM) is a complex metabolic disorder involving insulin resistance, impaired insulin signaling and \(\beta\)-cell dysfunction, and abnormal glucose and lipid metabolism. Hyperglycemia is the most important criterion for all types of diabetes and is the cause of diabetic complications such as CVD. Therefore, it is important to prevent or delay the onset of diabetes by controlling blood glucose levels in diabetic patients, as hyperglycemia increases the risk of developing CVD long before clinical diabetes begins [43]. In humans, \(\alpha\)-glucosidase and \(\alpha\)-amylase in the small intestine play an important role in the digesting dietary carbohydrates into glucose. Therefore, reducing postprandial hyperglycemia by delaying the absorption of glucose in the body through the inhibition of \(\alpha\)-amylase and \(\alpha\)-glucosidase is an important approach for treating T2 DM [44; 45]. The enzyme inhibitors used for this action suppress the digestion of carbohydrates and consequently slow the postprandial plasma glucose rise, thereby delaying the rate of glucose absorption [46].