# Therapeutic Potential of Seaweed-Derived Bioactive Compounds for Cardiovascular Disease Treatment
## 2 Seaweed-Derived Phlorotannins with Therapeutic Potential against CVD
Because the AMPK system plays an important role in glucose homeostasis, it is a key target for discovering anti-diabetic agents [59]. Some evidence has demonstrated that 2,7\"-phloroglucinol-6,6'-bieckol isolated from _E. cava_ protects against high glucose-induced glucotoxicity and apoptotic cell death in INS-1 cells [60] (Table 1). In addition, in C57 BL/KsJ-db/db mice, the oral administration of 20 mg/kg dieckol isolated from _E. cava_ significantly reduced blood glucose levels, serum insulin levels, and body weight [61]. [PERSON] et al. demonstrated that oral administration of isophloroglucin A (IPA) and oxtaphlorethanol A (OPA) isolated from _I. okamurae_ and _I. foliacea_ significantly ameliorated glucose intolerance and the fasting glucose levels in high-fat diet (HFD)-fed mice, thereby reducing fasting and 2 h blood glucose levels, as well as stimulated GLUT4 in HFD mouse muscle [62; 63]. Furthermore, phlorotannins such as DPHC and IPA isolated from _I. okamurae_ treatment exhibited an anti-angiogenic effect by interfering with the VEGFR-2 signaling pathway [64; 65]. These phlorotannin compounds isolated from various seaweeds exhibit anti-diabetic efficacy through various mechanisms in vivo and in vitro, demonstrating the potential as natural agents that can replace synthetic anti-diabetic treatments. Despite the evidence suggesting that type 2 diabetes mellitus might be caused by more complex molecular pathways implicated in cell biology, the main concepts of treatments still mainly focus on the pathway we mentioned above, and clinical trials using single compounds isolated from seaweeds have not been reported. Despite its relatively simple definition, obesity, defined as excess body fat, is a complex condition resulting from a chronic positive energy balance when the dietary energy intake exceeds energy expenditure. Excess energy is converted to triglycerides and stored in adipose tissue depots, expanding in size, producing weight gain, and increasing body fat. The adipose tissue includes several types of cells, such as mature adipocytes, pre-adipocytes, fibroblasts, endothelial cells, and immune cells [66]. Adipose tissue undergoes dynamic histological changes as obesity progresses, including adipocyte enlargement, enhanced angiogenesis, immune cell infiltration, and extracellular matrix overproduction [67]. In contrast, adipocytes undergo differentiation, and specific proteins, including sterol regulatory element-binding protein 1 (SREBP1c), CCAAT/ enhancer-binding protein (C/EBP\(\alpha\)), and peroxisome proliferatorator-activated receptor \(\gamma\) (PPARy) are involved in all processes [68; 69]. Several lines of evidence indicate that the phlorotannins contained in seaweed such as _E. cava_ (eckol, dieckol, triphlorothol-A, 6,6'-bieckol, and phlorofucoeckol A), _Ecklonia stolonfera_ (phloroglucinol, eckol, dieckol, dioxinodehydroeckol, and phlorofuco-fluoroeckol A), _Eisenia bicyclis_ (6,6'-bieckol, 6,8'-bieckol, 8,8'-bieckol, and dieckol, phlorofuco-fluoroeckol A), and _I. okamurae_ (diphlorothohydroycarmalol) exhibit anti-obesity properties by inhibiting intracellular lipid accumulation, suppressing adipogenesis in 3T3-L1 cells via inhibiting the expression of PPARy, C/EBP\(\alpha\), SREBPP-1, and FABP4, and activating AMP-activated protein kinase (AMPK) and ACC phosphorylation [70; 71; 72; 73; 74; 75; 76; 77] (Table 1). In addition to these mechanisms, some phlorotannins isolated from brown seaweed exhibited anti-obesity effects by reducing leptin resistance or inhibiting pancreatic lipase [78; 79]. Additionally, oral administration of phlorotannins such as eckol and dieckol isolated from _E. cava_ and _Ecklonia stolonfera_ showed antihyperlipidemic effects by decreasing the total cholesterol levels, triglyceride levels, and low-density lipoprotein levels and increasing the high-density lipoprotein in the serum of high-fat diet mice [80; 81].