Seaweeds (otherwise known as algae) are neither plants, animals, bacteria or fungi, but are plant-like organisms that share some morphological and physiological characteristics with plants, and grow in marine environments. Like plants on land they are incredibly diverse and are a valuable source of bioactive compounds with therapeutic and other potential uses.
Seaweeds have long been incorporated into the diet of many traditional coastal communities, and are rich sources of proteins, vitamins, and minerals such as iron and iodine. Practitioners of herbal medicine also recommend or prescribe seaweed preparations for an underactive thyroid, or where mineral deficiencies are perceived.
The use of seaweeds or algae extracts in human health is nothing new, with agar (from algae such as Gracilaria, Gigartina and Gelidium) being used as a gelling agent and growth medium in microbiology, and extracts from Chondrus crispus (Irish Moss) used to thicken suspensions and syrups, and as a popular cough remedy. In recent decades, marine algae have attracted increased attention as a natural source of ingredients and bioactive constituents for medicines, cosmetics, and dietary supplements(1).
Spirulina and astaxanthin
The blue-green microalgae Spirulina for example, is rich in many vitamin and essential nutrients, beta-carotene and protein, and has antioxidant, anti-inflammatory and anti-diabetic properties(2, 3). It is now cultivated in both sea and freshwater farms, to meet a large global demand.
Astaxanthin is a xanthophyll carotenoid found in various species of algae as well as yeast, salmon, trout, krill, shrimp and crayfish. While commercial astaxanthin is mostly from Phaffia yeast, Haematococcus pluvialis (a freshwater green microalgae) is one of the best sources of natural astaxanthin.
It has become increasingly popular as a nutritional supplement in recent years, with in vitro and in vivo studies associating it with health benefits. Its antioxidant, neuroprotective, cardioprotective and antitumoral properties suggest possible applications in the prevention or co-treatment of dementia, Alzheimers, Parkinsons, cardiovascular disease and cancer(4-6). Improved skin moisture content and elasticity, has also been reported following oral astaxanthin supplementation, and it is increasingly used in cosmetic formulations(7, 8). Evidence also suggests its usefulness in the prevention and treatment of eye conditions such as glaucoma, cataracts and uveitis, and to improve visual acuity and eye accommodation(4, 9, 10).
Polysaccharide complexes known as fucoidans isolated from brown seaweeds have also gained considerable attention lately, through their antioxidant, immunomodulatory, anti-inflammatory, antiobesity, antidiabetic, and anticancer properties(11, 12).
Wound dressing, drug delivery and scaffolding applications
Because of their high biocompatibility and biodegradability, and other unique physicochemical properties, marine biopolymers are ideal for the development of advanced systems for cell proliferation scaffolds, bioadhesives, release modifiers, and wound dressings(13).
Alginate dressings are light, highly absorbent fabrics made from seaweed derivatives and fibres, and can stay on the wound bed for days. Research into different species and applications has revealed several new potential applications, for conditions that are currently very difficult to treat(14, 15).
Alginate is also an ideal building block to promote therapeutic cellular regeneration, and alginate-based hydrogels are an attractive material for the application in cardiac regeneration and valve replacement techniques(16). Carrageenan based hydrogels also have applications to sustained drug release, in bone and cartilage tissue engineering and in wound healing and antimicrobial formulations(17).
Apart from their physical attributes making them suitable as wound dressings and drug delivery vehicles, numerous marine algae show direct antimicrobial activities.
A range of seaweed compounds including polysaccharides, fatty acids, phlorotannins, pigments, lectins, alkaloids, terpenoids and halogenated compounds, show antiviral, antiprotozoal, antifungal, and antibacterial properties(18-20). Much research is underway aimed at the identification and development of bioactive compounds and products that can be used as broad spectrum antibiotics, antibacterial, and antifouling agents(20, 21, 22).
The green algae sea lettuce (Ulva lactuca) has antibacterial activity including against methicillin-resistant Staph aureus, and shows potential applications in wound preparations(23).
Phlorotannins are a type of tannin occuring as complex polymer mixtures and found only in some seaweeds, and many exhibit good antimicrobial activities. Those from the Atlantic ocean brown seaweed, Fucus vesiculosus, demonstrate bacteriostatic action against Staph. aureus and Strep. pneumoniae(24-27). Another weakens resistance mechanisms of acne-related bacteria to antibiotics such as erythromycin and lincomycin(28). Compounds from Arame seaweed (Eisenia bicyclis) promote cell membrane damage and reduce expression of methicillin resistance-associated genes in Staph. aureus(29).
Regular oral administration of ascophyllan, a sulphated polysaccharide from the edible brown alga Ascophyllum nodosum, before and after bacterial infection resulted in a remarkable increase in survival rate in mice with a severe intranasal Streptococcus pneumoniae infection(25).
A recent review of studies using marine algal extracts against oral cariogenic bacteria, identified many as having anti-microbial properties and showing potential for oral hygiene maintenance(30).
Polyphenolic compounds and polysaccharides from marine algae also show potential for the discovery and development of new antiviral treatments. In vitro activity has been shown for many sulfated polysaccharides, including carrageenan, agar, ulvan, fucoidan, and alginates. Mechanisms of antiviral actions include blocking the initial entry of the virus or inhibiting its transcription and translation by modulating the immune response of the host cell(31-35). Many of these agents have anti-inflammatory and immunomodulatory actions that may also be relevant to the management of chronic viral infections or their complications. Several sulfated polysaccharides have been identified as potential antiviral agents against the COVID-19 virus(35, 36, 37). However, further preclinical and many more clinical studies are still required to establish the roles that seaweed extracts or compounds might have, in the management of viral infections.
Apart from potential applications in human medicine, microalgae and their antimicrobial compounds are also being investigated as biocontrol agents against food and plant pathogens(38).
The mucilaginous properties of polysaccharides found in many seaweeds can make them useful in the management of digestive conditions such as dyspepsia or peptic ulcers. Anti-inflammatory, anti-ulcerogenic and gastroprotective activities have been reported for algae from different parts of the world(39, 40, 41). These include the Mediterranean red algae, Laurencia obtusa(39), and a Malaysian red algae Gracillaria changii which showed comparable protection to omeprazole against gastric lesions in rats(40).
Fucoidan has anti-ulcer effects, and can prevent the adhesion of Helicobacter pylori to gastric epithelial cells, and reduce biofilm formation(42-44).
Algal metabolites exhibit protective effects against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis, known factors in many neurological disorders and neurological complications after strokes and brain injuries(45, 46).
Drugs and substances that inhibit the enzyme cholinesterase (known as cholinesterase inhibitors), are used to alleviate symptoms of dementia and Alzheimer’s disease, and to treat myasthenia gravis and glaucoma. Research up until 2018 identified and reported 185 marine cholinesterase inhibitor and selected analogue compounds, some of which displayed inhibitory activities comparable or superior to cholinesterase inhibitor drugs in clinical use(47).
Of these and the many other algal compounds with promising neuroprotective capacity identified to date however, few have had access to clinical trials. Encouragingly though, a marine oligosaccharide, sodium oligomannate, has recently been found to improve cognition in a 36 week Phase 3 clinical trial in patients with mild to moderate Alzheimer’s disease(48).
Potential applications extend also to the treatment of depression, with favourable results from animal and in vitro studies on some extracts, but human studies are lacking(49).
The search for new anti-cancer drugs is ongoing, and many promising compounds and extracts have been discovered through bioprospecting under the sea(50-56).
The anti-leukaemic drug cytarabine is derived from arabinose-containing nucleotides from the Caribbean marine sponge Cryptotheca crypta, and the breast cancer drug eribulin, from the Japanese marine sponge Halichondria okadai. New marine-derived substances with anticancer activities are continuously being isolated and tested, with several currently in clinical trials(57-58).
One such substance is phycocyanin, a biliprotein constituent of Arthrospira platensis with several therapeutic properties, including anti-oxidant, anti-inflammatory, immune-modulatory and anti-cancer activities(59). Other promising compounds include the leptosins, isolated from the fungus Leptoshaeria spp an endophyte of the macroalgae Sargassum tortile(53).
Other potential uses:
Fucoidan and other algae compounds exhibit a range of osteogenic effects, including stimulation of osteoblast activity and mineralisation, as well as suppression of osteoclast resorption. This suggests a potential to assist with bone growth and healing(60).
Hepatoprotective and endotoxin-protective effects have also been reported for fucoidan, spirulina and other algae extracts(63, 64).
Red and brown algae are reported to show anti-diabetic activity. Possible actions include protection against chronic metabolic disease and diabetes mellitus, and complications such as retinopathy, atherosclerosis and nephropathy(61). Red algae species, Chondrus crispus, Porphyra tenera and Schizymenia binderi, produce sulfated polysaccharides known as galactans which have anticoagulant activities(13, 65).
Alginate has detoxification abilities and potential to chelate metals and reduce cholesterol and blood pressure(62).
Apart from their health benefits, the potential toxicity, mechanisms of action, and interactions of seaweeds with conventional foods, are areas requiring more attention.
Excessive ingestion of many seaweeds can cause high exposure to iodine, which can lead to hyperthyroidism. High salt intake and thus an increased risk of hypertension and hypernatraemia, can also occur through regular ingestion of poorly processed seaweed as a food source.
As with land based plants, some seaweeds are toxic or produce toxic metabolites, and as such, correct species identity is important. Toxicity might also be due to epiphytic bacteria or harmful algal bloom and absorbed heavy metals from seawater(66).
Algae play a crucial role in aquatic ecosystems. A shortage of algae could lead to coastal erosion, loss of biodiversity, lower water quality, and numerous negative effects on the food chain and marine habitats. Similarly intensive and irresponsible aquaculture of algae has the potential to cause water and local environmental pollution, and a decline in wild species populations. The effects of trawling for fish on the entire underwater marine ecosystem, are also still poorly understood.
Worldwide, more than 200 species of marine algae are already being harvested from wild or cultivated sources, and commercially used.
While as a small country with a relatively large sea area Aotearoa New Zealand may seem immune from unsustainable activities, the growing interest and increasingly diverse applications being realised for algae may lead to their overexploitation, unless harvesting is well managed. Ocean pollution is also of growing concern and poses serious threats to human health, with downstream outcomes now only beginning to be understood(67). Nitrogen and phosphorous runoff from farms as well as climate change factors, contribute to algae “blooms” which can smother and harm other marine species including shellfish, and produce offensive smelling gases during rotting by bacteria.
On the promising side though, possible applications of certain seaweeds such as Asparagopsis spp as food supplements to cows in order to reduce greenhouse gas emissions, are emerging. A red macroalgae Asparagopsis spp. has been shown to cause an 80 percent reduction in methane production by cows(68). In Aotearoa New Zealand, the Cawthron Institute, seaweed and dairy industry are currently involved in field trials to see if Asparagopsis armata is a viable feed additive to significantly decrease the carbon footprint of cows. While early results are promising, wild seaweed harvest is unlikely to provide a reliable and sustainable supply, meaning that an aquaculture and selective breeding strategy, is likely to be required(69).
With our country being privileged to have a rich and highly biodiverse marine environment, and seaweeds clearly being an important source of new medicines in the future, a careful and measured approach to research and development and future commercialisation, is critical. Given this, it is good to see the Aotearoa New Zealand government, Cawthron Institute and elements of industry investing significantly into seaweed research, with a National Algae Research Centre being opened at the Cawhron Aquaculture Park in Nelson, in May last year.
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