Dietary changes in daily life are a major approach used to reduce the prevalence of chronic diseases, such as CVD
. Accordingly, various studies have begun to reveal that foods and their physiologically active components can affect CVD
. In this context, marine seaweeds have vast biodiversity because they are exposed to a wide range of environmental factors that differ from those of terrestrial plants, leading to the pro-duction of secondary metabolites with various characteristics and applicability. Various in vitro, in vivo, and clinical studies have reported on the efficacy of seaweeds and their natural products for reducing the risk of CVD
. For example, several studies have revealed an association between dietary intake of seaweed and increased life expectancy or reduced incidence of certain diseases, such as CVD
.
Supplementing the diets of hypercholesterolemic Wistar rats with 21% or 23% of
Himanthalia elongata or
Gigartina pistillata, which is equivalent to 8% dietary fiber for four weeks, improved the serum lipid profile as compared to in hypercholesterolemic Wistar rats without dietary intervention
[24]. The
Himanthalia diet significantly reduced the TG content by 28% and increased the HDL-C content by 20%. The diet containing
Gigartina improved the lipid profile by decreasing TG, TC, or LDL-C levels by 30%, 18%, and 16%, respectively. Villanueva et al. also found that seaweed intake improved the lipid profile
[24]. Kumar et al. reported that intake of
Derbesia tenuissima for eight weeks decreased plasma TG and TC levels by 38% and 17%, respectively, in rats fed a high-fat diet because of the insoluble fiber content (23.4%)
[25]. Chan et al. also found that
Gracilaria changii, which has a high dietary fiber content of 61.29%, significantly improved the lipid profile of high-cholesterol/high-fat Sprague Dawley rats
[26]. Rats fed a HF diet supplemented with 5% or 10%
G. changii exhibited significantly reduced plasma TC, LDL-C, and TG contents. In addition, changes in the lipid profile were observed even in rats given normal feed supplemented with
G. changii during the experimental period, but the authors explained that the lipid changes were caused by the normal growth process of the experimental model and were not related to the feed supplement. However, a change in the lipid profile of a normal animal model following seaweed intake was reported by Kim et al.
[27] and Ruqqia et al.
[29]. Kim et al. observed that
Ecklonia cava had lipid-lowering effects in both normal mice and streptozotocin-diabetic mice, demonstrating the potential of this supplement to prevent the progression of coronary heart disease. Jung et al.
[28] further evaluated the properties of phlorotannins from
Ecklonia stolonifera in vitro. In addition, various seaweeds, including
Rhizoclonium implexum,
Dictyota indica,
Padina pavonia,
Stoechospermum marginatum,
Stokeyia indica,
Jolyna laminarioides,
Sargassum binderi, and
Melanothamnus afaqhusainii showed lipid-lowering effects by reducing TC, TC and LDL-C and increasing HDL-C in normal rats according to Ruqqia et al.
[28]. The authors emphasized the medical importance of seaweed, as consumption of seaweed not only inhibited the progression of CVD, but also regulated the accumulation of lipids in daily life and may play an important role in improving the survival of humans. Based on the lipid-lowering effect in normal rats, Ruqqia et al. further investigated
J. laminarioides,
S. binderi, and
M. afaqhusainii for their antihyperlipidemic effects in Triton-induced hyperlipidemic rats and in high-fat diet-induced hyperlipidemic rats. They found that the brown seaweeds
J. laminarioides and
S. binderi significantly decreased TG levels by 31.6% and 33% in high-fat diet-induced hyperlipidemic rats. Jimenez-Escrig and Sanchez-Muniz reported that alginic acid and alginic acid isolated from brown algae play important roles in lowering blood cholesterol levels in rats by decreasing intestinal cholesterol absorption
[38]. Patil et al. noted that sulfated polysaccharides in brown algae delay the intestinal absorption of cholesterol or promote cholesterol excretion
[39]. Cuong et al. produced fucoidan, a sulfated polysaccharide from the brown seaweed
S. henslowianum, and found that it lowered cholesterol, TG, and LDL-C levels when administered orally at 100 mg/kgP/day to obese rats
[30]. The red seaweed
M. afaqhusainii, which contains 0.46 ± 0.01% sterols, also exerted lipid-lowering effects. In the 1970s, Bhakuni and Silva reported that cholesterol is the most commonly occurring sterol in red seaweed and can reduce blood cholesterol levels
[40]. In addition, Ruqqia et al. found that the non-toxic sterols of red algae can lower blood cholesterol and fat accumulation in the heart and liver
[29]. In a clinical study, carrageenans from red seaweed significantly decreased cholesterol levels (16.5%) and LDL-C levels (33.5%), leading to a reduced atherosclerotic index
[31]. Dousip et al. compared the cholesterol-lowering properties of the red seaweed
Kappaphycus alvarezii and brown seaweed
Sargassum polycystum [32].
Kappaphycus alvarezii contains 42.09 ± 0.97% carrageenan and
S. polycystum contains 8.98 ± 0.33% alginate.
Sargassum polycystum consumption significantly decreased the plasma cholesterol level by 37.52% over an eight-week treatment period compared to
K. alvarezii. Jiménez-Escrig and Sánchez-Muniz reported that the antihyperlipidemic activity of alginate in brown algae is affected by the degree of polymerization
[38]. Accordingly, Dousip et al. explained that the cholesterol-lowering effect was lowered as the alginate of
S. polycystum contained a high-molecular weight alginate polymer
[32]. In addition, the beneficial effects of polysaccharides and ulvans in green seaweed extracted from
Ulva fasciata,
Ulva lactuca, and
Monostroma nitidum were suggested to improve lipid profiles
[33][34][35]. Marine-derived active components such as fucoidan and fucoxanthin have also been evaluated and shown to have beneficial effects on lipid profiles in in vivo models
[36][37].
3. Marine Natural Products Affect Endothelial Dysfunction
Atherosclerosis, mainly caused by hypertension and dyslipidemia, begins with dysfunction of vascular endothelial cells and develops into CVD via plaque accumulation and related lesion formation in the blood vessels
[12].
Vascular endothelial dysfunction is caused by (1) decreased eNOS activation by reduced intracellular Ca
2+ level in the endothelium, (2) decreased bioavailability of nitric oxide produced from eNOS, (3) increased production of endothelial-derived vasoconstrictor factors, and (4) increased levels of oxidative stress and inflammation-inducing cytokines
[41] (
Figure 1).
Table 2 shows the effects of various seaweed components on endothelial dysfunction in in vitro and in vivo models.
Figure 1. Crosstalk between endothelium (EC) and vascular smooth muscle cells (VSMCs) in hypertension.
Table 2. Effects of seaweed components on endothelial dysfunction.
Alam et al. reported that the natural carotenoid astaxanthin extracted from microalgae
Haematococcus pluvialis can penetrate the endothelial cell membrane and significantly inhibit ROS, thereby inhibiting oxidative stress in ISO-induced myocardial infarction and cardiac hypertrophy in rats, suggesting its cardioprotective action
[42]. Zhao et al. found that astaxanthin protects against endothelial dysfunction of the aorta in diabetic rats and predicted the molecular mechanism involved in their effects
[43]. They suggested that astaxanthin can attenuate blunted endothelium-dependent vasodilator responses to acetylcholine, upregulate endothelial nitric oxide synthase expression, and decrease excessive oxidative stress and endothelial dysfunction. Lee et al. isolated dieckol from the brown seaweed
E. cava and found that it protected human umbilical vein endothelial cells damaged by high glucose via its antioxidant properties
[44]. In addition, the positive effects of eckol and its derivatives, including dieckol from the brown seaweed
Ecklonia bicyclis, were investigated in both human umbilical vein endothelial cells and mice
[45]. They suggested that the abundance of hydroxyl groups of eckol and its derivatives contribute to their vascular barrier protective functions. Another phlorotannin, diphlorethohydroxycarmalol (DPHC) isolated from
Ishige okamurae, was observed to have vasodilatory effects by increasing nitric oxide production and Ca
2+ release in endothelial cells via stimulating the Ach receptor and VEGF-receptor 2
[46]. The author further demonstrated the vasodilatory ability of DPHC in Tg(flk:EGFP) transgenic zebrafish. In addition, another crucial components in brown seaweed, the sulfated polysaccharides extracted from
Padina tetrastromatica, were investigated for their effect on ISO-induced myocardial infarction in a rat model
[47]. ISO-induced hyperlipidemia, endothelial dysfunction, and inflammatory reactions were significantly reduced by the sulfated polysaccharides. Specifically, the authors emphasized that sulfated polysaccharides can be used as a new functional food ingredient for CVD, as they showed therapeutic ability similar to that of aspirin, a reference drug.