Marine polyphenols are a diverse group of compounds that include flavonoids, phenolic acids and stilbenes, among others. They are synthesized by marine organisms as a defense mechanism against environmental stressors, such as UV radiation, pathogens and predators [
3]. Marine polyphenols have been found to exhibit a wide range of biological activities, including anti-inflammatory, anticancer, antiviral, antimicrobial and neuroprotective effects [
19].
One of the key mechanisms by which marine polyphenols exert their biological effects is through their ability to interact with cellular signaling pathways. For example, marine polyphenols have been found to modulate the activity of the enzymes involved in cell proliferation, differentiation and apoptosis [
194]. This can lead to the inhibition of cancer cell growth and the induction of cell death. Marine polyphenols can also regulate the expression of genes involved in inflammation, such as cytokines and chemokines, thereby reducing inflammation [
195].
Marine polyphenols can also modulate the gut microbiota, which has important implications for human health. The gut microbiota plays a critical role in nutrient absorption, immune function and metabolic homeostasis [
199]. Polyphenols can affect the composition and activity of the gut microbiota, promoting the growth of beneficial bacteria and reducing the growth of harmful bacteria. This can lead to improved gut health and a reduction in the risk of chronic diseases such as inflammatory bowel disease, obesity and type 2 diabetes [
200].
4.1. Therapeutic Potential of Marine Polyphenols
4.1.1. Cardiovascular Diseases
Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide, and marine polyphenols have been studied extensively for their potential therapeutic effects in CVDs. Some of the ways in which marine polyphenols may be beneficial in CVDs [
115] are as follows:
Antioxidant activity: Marine polyphenols have strong antioxidant properties, which can help reduce oxidative stress in the cardiovascular system. Oxidative stress has been implicated in the development and progression of CVDs, and reducing it may help improve cardiovascular health. Some of the main marine polyphenolic compounds with antioxidant activity include [
204]:
Phlorotannins: These are a group of complex polyphenolic compounds found in brown seaweeds. Phlorotannins are known for their potent antioxidant activity, and they have been shown to have a wide range of health benefits, including anti-inflammatory and anti-cancer properties [
15].
Catechins: These are flavonoid polyphenolic compounds found in green tea and some marine sources, such as seaweed [
17]. Catechins have been shown to have potent antioxidant properties, and they may help reduce the risk of cardiovascular disease and other chronic diseases [
158].
Anti-inflammatory effects: Chronic inflammation is a key factor in the development of CVDs, and marine polyphenols have been shown to possess anti-inflammatory effects. By reducing inflammation, these compounds may help protect against CVDs [
206]. Some of the most commonly studied compounds in this regard include:
Fucoidan: This is a sulfated polysaccharide found in brown seaweed and has been shown to possess anti-inflammatory effects by inhibiting the production of pro-inflammatory cytokines [
207].
Phlorotannins: These are polyphenolic compounds found in brown seaweed and have been shown to possess anti-inflammatory effects by inhibiting the production of pro-inflammatory enzymes such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) [
145].
Fucoxanthin: This is a carotenoid pigment found in brown seaweed and has been shown to possess anti-inflammatory effects by inhibiting the production of pro-inflammatory cytokines and reducing oxidative stress [
20].
Eckol: This is a phlorotannin found in brown seaweed and has been shown to possess anti-inflammatory effects by inhibiting the production of pro-inflammatory cytokines and reducing oxidative stress [
208].
Astaxanthin: This is a carotenoid pigment found in microalgae and has been shown to possess anti-inflammatory effects by inhibiting the production of pro-inflammatory cytokines and reducing oxidative stress [
209].
Regulation of lipid metabolism: Dyslipidemia, or abnormal lipid levels in the blood, is a major risk factor for CVDs. Marine polyphenols have been shown to regulate lipid metabolism, potentially reducing the risk of CVDs [
210]. Some of the main marine polyphenolic and other minor compounds that have been shown to regulate lipid metabolism and potentially reduce the risk of CVDs are:
Fucoxanthin: This is a carotenoid pigment found in brown seaweed. Fucoxanthin has been shown to reduce body weight, decrease total cholesterol and improve lipid metabolism in animal studies. It works by inhibiting the enzymes involved in the synthesis of cholesterol and triglycerides [
211].
Astaxanthin: This is a carotenoid pigment found in microalgae, yeast, salmon, trout, krill, shrimp, crayfish, crustaceans and the feathers of some birds. Astaxanthin has been shown to improve lipid metabolism by decreasing serum triglyceride and cholesterol levels. It also exhibits antioxidant and anti-inflammatory properties [
213].
Vasodilatory effects: Some marine polyphenols have been shown to have vasodilatory effects, meaning they can help relax blood vessels and improve blood flow. This can help reduce blood pressure and improve cardiovascular health [
214]. Some of the main marine polyphenolic and other minor nutrients that have been shown to regulate lipid metabolism and potentially reduce the risk of CVDs are:
Fucoxanthin: This is a carotenoid pigment found in brown seaweed. Fucoxanthin has been shown to reduce body weight, decrease total cholesterol and improve lipid metabolism in animal studies. It works by inhibiting the enzymes involved in the synthesis of cholesterol and triglycerides [
215].
Phlorotannins: These are a group of polyphenolic compounds found in brown seaweed. Phlorotannins have been shown to reduce serum lipid levels by inhibiting the absorption of dietary fat and cholesterol. They also exhibit antioxidant and anti-inflammatory properties [
216].
Fucoidan: This is a sulfated polysaccharide found in brown seaweed. Fucoidan has been shown to decrease triglyceride levels and improve lipid metabolism in animal studies. It works by inhibiting the activity of the enzymes involved in the synthesis of triglycerides [
217].
Platelet inhibition: Platelet activation and aggregation play a key role in the development of thrombosis, which can lead to heart attacks and strokes. Marine polyphenols and other minor nutrients have been shown to inhibit platelet aggregation, potentially reducing the risk of thrombosis [
218]. Some of the main ones are:
Fucoidan: Fucoidan is a sulfated polysaccharide found in various types of brown seaweed. It has been shown to inhibit platelet aggregation by inhibiting the binding of platelet activating factors to platelet receptors [
219].
Phlorotannins: Phlorotannins have been shown to inhibit platelet aggregation by interfering with the release of platelet activating factors [
220].
Catechins: Catechins, a type of flavonoid found in many types of seaweed, can inhibit platelet aggregation by inhibiting the activity of platelet-activating factors and reducing the adhesion of platelets to the blood vessel wall [
221,
222].
Eckol: Eckol is a type of phlorotannin found in brown seaweeds. It has been shown to inhibit platelet aggregation by interfering with the binding of platelet activating factors to platelet receptors [
223].
4.1.2. Diabetes
Among the marine polyphenols that have been studied for their potential therapeutic effects in diabetes, some of the most commonly studied include:
Fucoxanthin: This polyphenol has been shown to have anti-diabetic effects by improving insulin sensitivity and glucose metabolism in animal studies [
224].
Phlorotannins: These polyphenols have been shown to have anti-diabetic effects by reducing blood glucose levels and improving insulin sensitivity in animal studies [
225].
Fucoidan: This polysaccharide has been shown to have anti-diabetic effects by improving glucose metabolism and insulin sensitivity in animal studies [
6].
Bromophenols: These polyphenols have been shown to have anti-diabetic effects by reducing blood glucose levels and improving insulin sensitivity in animal studies [
226].
Catechins: These polyphenols have been shown to have anti-diabetic effects by improving insulin sensitivity and glucose metabolism in animal studies.
4.1.3. Neurodegenerative Diseases
Neurodegenerative diseases are a group of chronic and progressive disorders that affect the nervous system and lead to the gradual loss of function of neurons. They include Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, among others. The pathogenesis of these diseases is multifactorial and involves oxidative stress, inflammation and the accumulation of misfolded proteins [
237].
Marine polyphenols are natural compounds found in various marine organisms, including seaweeds, algae and marine animals. They have been shown to possess a wide range of biological activities, including antioxidant, anti-inflammatory and neuroprotective effects. Therefore, marine polyphenols have been investigated for their therapeutic potential in the prevention and treatment of neurodegenerative diseases [
9].
The antioxidant properties of marine polyphenols can help reduce oxidative stress in neurons, which is a major contributor to neurodegeneration [
238]. These compounds have been shown to scavenge free radicals, prevent lipid peroxidation and enhance the activity of antioxidant enzymes. Moreover, marine polyphenols can also modulate inflammatory pathways, reducing the release of pro-inflammatory cytokines and chemokines that contribute to neuronal damage [
2].
Marine polyphenols have also been found to have neuroprotective effects by inhibiting the aggregation of misfolded proteins, such as amyloid-beta and tau in Alzheimer’s disease and alpha-synuclein in Parkinson’s disease. By preventing the accumulation of these proteins, marine polyphenols can help maintain neuronal function and prevent neuronal death [
239].
Overall, the therapeutic potential of marine polyphenols in neurodegenerative diseases is promising, but more research is needed to fully understand their mechanisms of action and to develop effective treatments. Further studies should focus on identifying the most potent marine polyphenols and optimizing their delivery to the brain to maximize their therapeutic effects [
240].
4.1.4. Cancer
As described earlier, polyphenols and other micronutrients are bioactive compounds found in plants and animals, and recently there has been a growing interest in marine polyphenols due to their therapeutic potential in several areas of health, including cancer [
2,
254].
Marine polyphenols are extracted from marine organisms such as algae, mollusks, corals, sponges and fish. They have a wide variety of health benefits, including antioxidant, anti-inflammatory, anticancer and immunomodulatory activities [
255].
The anticancer activity of marine polyphenols has been observed in several in vitro and in vivo studies. They are able to induce cell death in cancer cells, inhibit cell proliferation, inhibit angiogenesis and modulate the immune response. These effects are important because uncontrolled cell proliferation, excessive angiogenesis and suppression of the immune response are hallmarks of tumor development [
256].
Ellagic acid is a polyphenol present in kelp that has been shown to cause cell death in breast and colorectal cancer. It functions by blocking the expression of pro-inflammatory and pro-angiogenic genes in cancer cells. It has also been shown to boost the production of tumor suppressor proteins [
257].
Phloroglucinol acid is another polyphenol found in marine sponges with anticancer activity against lung and prostate cancer cells. This polyphenol induces apoptosis (programmed cell death) in cancer cells and inhibits the formation of capillaries that are necessary for angiogenesis [
138].
Another micronutrient of marine origin with therapeutic potential is fucoidan, a sulfated polysaccharide found in brown algae. Studies suggest that fucoidan has anticancer activity against several cancer cell lines, including breast, lung and colon cancer cells. This sulfated polysaccharide inhibits angiogenesis, modulates the immune response and induces apoptosis in cancer cells [
258].
5. Safety and Toxicity of Marine Polyphenols
Marine polyphenols are natural substances found in a variety of aquatic creatures, including seaweed, algae and shellfish. These compounds have received a significant amount of attention because of their possible health advantages, which include antioxidant, anti-inflammatory and anti-cancer properties. However, concerns have been raised regarding their safety and toxicity [
9,
18], mostly regarding their extraction and isolation methods, which can change their relative safety and toxicity; due to the diverse chemical structure and impurities, there is a need to standardize the procedure from extraction until the safety/toxicity assays.
Several studies have investigated the safety of marine polyphenols and their potential toxicity. Overall, the available evidence suggests that these compounds are generally safe for human consumption. However, there are some concerns regarding their potential toxicity at high doses [
19]. To date, the bioavailability of seaweeds has not been well researched. More research and study are required in this sector. The majority of seaweed phenolic pharmacological and biological bioavailability investigations have used mice models. Animal investigations and in vitro studies have provided evidence that seaweed phenols protect against various illnesses. As a result, fresh research investigations are required to investigate and completely comprehend their bioavailability in humans (the proportion of the chemical that reaches the human circulatory system and has an active impact).