Spirulina is a freshwater algae that originates from the natural environment and is filled with wonders, mysteries, and value. It has been considered a valuable food and medicine by various civilizations throughout history and was widely consumed by Native Americans, for instance. With the advancements in modern science and technology and the growing focus on health and nutrition, spirulina has also gained prominence as a high-profile nutritional supplement and pharmaceutical raw material. Spirulina is abundant in a variety of nutrients, including high-quality protein, various vitamins, and minerals, and plays a crucial role in human health and the prevention of various diseases. Additionally, spirulina finds extensive applications in the food, medicine, cosmetics, and other industries, indicating its broad prospects [1]. To meet the demand for spirulina, there are various cultivation methods available, such as natural culture, artificial culture, and continuous culture. Among these, continuous culture is a commonly used method that enhances the yield and growth rate of spirulina. Furthermore, methods like ultrasonic cell wall breaking and enzymatic hydrolysis are often employed to extract the active components in spirulina [2]. Research has demonstrated that ultrasonic breaking of cell walls is an effective extraction method that preserves the nutrients and antioxidant components in algal cells [3–5]. Apart from its use as food and pharmaceutical ingredients, spirulina has several potential applications. In recent years, researchers have discovered that spirulina metabolites can serve as raw materials for biofuels and biomaterials, offering high economic value [6, 7]. Additionally, studies have shown that spirulina can be utilized for purifying wastewater, soil, and air to address environmental pollution concerns. Over the past two decades, significant progress has been made in understanding the nutritional value and applications of spirulina, with researchers extensively exploring its nutritional components, cultivation methods, extraction techniques, and other aspects. Numerous studies have highlighted the immense potential of spirulina in promoting health and treating ailments [8]. In recent years, there has been a growing focus on using spirulina as a raw material for biofuels and biomaterials, with researchers striving to maximize its value, thereby catalyzing a surge in green industries centered around microalgae. In this context, this article aims to delve into the nutritional value of spirulina and its research applications in fields like food, medicine, cosmetics, treatment, biofuels, etc., providing an overview of the current research status and future prospects of spirulina [9, 10]. In an era where significant advancements have been made in this research field, examining the future development and application of spirulina not only deepens our understanding of its nutritional value and potential applications but also emphasizes the need for more healthy, green, and sustainable natural resources like spirulina in terms of health, medicine, and energy. Later due to outbreak of contagious disease, new customs were adopted by people such as new food, religious and social changes and the topic of tecuitlatl came to an end . Spirulina-“small cakes made of mud like algae, which has a cheese-like flavor, and that natives took out of the lake to make bread”. They are dried into cakes called “Diha” or “Die”.Some of

the best worldwide known Spirulina producing companies are earthrise farms (USA), Cyanotech (USA), Hainan DIC microalgae co ltd (China).

Morphology Under light microscopy, the blue-green non-heterocystous filaments, composed of vegetative cells that undergo binary fission in a single plane, show easily visible transverse cross-walls. Filaments are solitary and free floating and display gliding motility. The trichomes, enveloped by a thin sheath, show more or less slightly pronounced constrictions at cross-walls and have apices either slightly or not at all attenuated.Spirulina is characterized by its regularly coiled trichomes. Under some conditions of temperature and pressure, its helical filaments can convert to abnormal morphologies, such as irregularly curved and even linear shapes, that are considered as a permanent degeneration that could not be reversed. However, the linear filaments of Spirulina platensis could spontaneously revert to the helical form with the same morphology as the original filaments. The ultra structural, physiological, and biochemical characteristics of linear filaments are different from those of the original filaments, whereas they are the same for the reverted and the original filaments.

Ultra-Structure

It is a prokaryotic organization with fibrils of DNA region. Spirulina has photosynthetic system, plucri-stratified cell wall, capsule, ribosome and numerous inclusions. Cell wall is made of four membered layers: L1, L2, L3, and L4.

Life cycle

There are three fundamental stages: Trichomes fragmentation, Hormogonia cells enlargement and Maturation processes, and Trichome elongation. Then this mature trichomes get divided into filaments or hormogonia, cells in the hormogonia gets increased by binary fission, grows length wise and takes their helical form.

Cultivation of Spirulina

Spirulina is a blue green micro alga. It is an excellent source of proteins, beta-carotene, B vitamins and minerals like iron. It is a wonder food especially for the undernourished people. Hence its cultivation is also encouraged in the domestic levels of the developing countries who

are the worst victims of chronic malnutrition. Spirulina also proves to fetch them good amount of economy. Spirulina is a nutritious protein food supplement and is also used in the manufacture of several medicines, and cosmetics. Its cultivation on a commercial scale is slowly catching up with many farmers in India, particularly in Tamil Nadu. Spirulina is cultivated both for the commercial purpose as well for the domestic use in certain regions that are badly hit by chronic malnutrition and other deficiency diseases. The domestic house hold level cultivation of spirulina is very beneficial.

Domestic cultivation of Spirulina

The domestic cultivation method is well known as the "Mud Pot Spirulina Cultivation". This method requires mud pots of 35 to 40 liters capacity and an exposed but protected open area. The medium for the cultivation is the bio-gas slurry which is very cheap and easily available. Then, the sea-salt, Potassium dihydrogen Phosphate, Cooking Soda and Sodium Chloride, all this is mix for pure Spirulina culture. The method of working is very simple. All thees pots are buried till the neck in the ground. These are then filled with water and the slurry medium. Next the pure Spirulina culture is added to the pots. These are to be kept in sunlight and need to be stirred at least 4 times a day. After 3-4 days of maturation the Spirulina is ready. It is now filtered in clean cloth and then washed in fresh water. Spirulina can be immediately used for consumption or if a powdered form is desired it should be dried immediately.

Cultivation of Spirulina for personal consumption

Spirulina Platensis can be cultivated for personal use in a basin. There are many ways of building an adequate basin depending on variables according to local conditions: out of plastic covers, hard clay, low walls. It is generally useful, to install a greenhouse or at least a roof on the basin to protect it from the bad weather to minimize the risk of contamination. The roof can be made of white or translucent plastic, or other solutions making it possible to let pass a part of the light. To cultivate Spirulina it is necessary to recreate the close culture medium in which the micro?algae grows naturally. The culture medium is a controlled salt solution in water that provides to Spirulina all the necessary chemical elements essential for its cultivation. The pH of the culture medium should be between 8.0 and 11 (basic).

The material used for the cultivation of Spirulina is a basic stock of Spirulina that can be procured from scientific agencies or Spirulina farms. These stocks multiply in the culture medium by themselves also periodical control of the morphology of Spirulina may be necessary to exclude mutagen effect due to change in the chemical composition of the culture solution and because of the environmental factors. Spirulina are the carbon consuming micro?algae that consume carbon dioxide as in photosynthesis; one can increase the influx of Carbon dioxide, by composting under the greenhouse contiguous to the basin. The ideal temperature for Spirulina Cultivation is between 35°C and 37°C.The water level of the basin should be controlled and it should be a minimum of 20 cm. Water should be added when necessary not impacting the chemical composition or pH of the culture medium. Agitation of the water of the basin is necessary to homogenize and ensure a good distribution of lighting among all the filaments of Spirulina. Agitation can be done manually with a clean brush or a wheel, 4 times per day, for 2 minutes. Spirulina is harvested by skimming the surface of the basin and to initially filter Spirulina in a filter such as a mosquito net. It is further filtered in a filter of dimensions of 60 microns. Spirulina collected after filtration and reduced in fine powder is stored in plastic bag/container. Though Spirulina can be consumed fresh, it can also be used after slight drying. It is better to consume Spirulina within 6 hours of its harvest but can be preserved for later consumption for a period of up to one year by drying it in the sun or in a solar drier. To store Spirulina for a much longer time, it is vacuum dried and packed air?tight where it sustains its nutritional qualities for five years.

Commercial Cultivation

Spirulina is a simple, one-celled form of blue-green algae that gets its name from its spiral shape. The product is currently being hailed as the super food of the future because of its exceptional nutritional content. Spirulina is a better source of protein than either beef or soyabean. The process involves inoculation of Spirulina culture in tanks having mechanized agitators to oxygenate the water. About 20-25 gm of Spirulina grows in 1.0 sq. meter surface area of water in a day. The blue-green algae is removed from water surface and allowed to dry before purification and production of powder by spray drying process. It can be produced in very low cost and high cost depending upon the quality standard of infrastructure facility, production quality parameters and standardization of product followed .Internationally, customer are willing to pay for the product is premium price and so high end technology can equally viable as in the case low end. A lot of value added health drinks and products can be generated by using this alga. The Spirulina that is to be used for the commercial purpose is cultivated in a different way. The commercial Spirulina is grown open-channel shallow artificial ponds. Here, the paddle-wheels are used to stir the water so as to accelerate the growth of Spirulina. The largest commercial production of Spirulina is carried out in United States, Thailand, India, Taiwan, China, Pakistan and Myanmar. Phycobilin is the primary protein found in spirulina, consisting of three proteins: phycocyanin, allophycocyanin, and phycoglobin. Leonard and Compere determined that the protein content in spirulina was approximately 50% of its dry weight [11]. Phycocyanin, the fundamental building block of phycobilin, is composed of ? and ? chain globulin subunit monomers that polymerize to form various structures, including trimers and hexamers. It exhibits light absorption capabilities within the range of 550–630 nm, with a maximum absorption wavelength of 610–620 nm and a molecular mass of 44–260 kDa. The ? subunit of phycocyanin contains 2 cysteine and 2 methionine residues, with a molecular weight of 12-19 KDa. On the other hand, the ? subunit contains 3 cysteine and 5 methionine residues, with a molecular mass of 14–21 KDa. Each subunit consists of 160–180 amino acid sequences. The phycocyanin molecule (Figure 1) possesses three chromophore groups attached to

Fig. 1 Global assessment of research and development for algae biofuel production and its potential role for sustainable development in developing countries

the alpha-84, beta-84, and beta-155 positions, respectively. Phycocyanin has a molecular weight of 44 kDa, an isoelectric point of 4.3, and a maximum absorption wavelength of 620 nm. Furthermore, studies have demonstrated that the amino acid sequences of ? subunits (or ? subunits) of phycocyanin from different species exhibit high homology, and their crystal structures are also remarkably similar [12]. Phycocyanin is a protein with diverse physiological activities, primarily promoting protein absorption and exhibiting antioxidant, anti-tumor, and anti-inflammatory properties. Additionally, phycocyanin effectively dissipates heat and can be utilized as a natural pigment in food and cosmetics [13, 14].

Polysaccharides

The polysaccharide of Spirulina platensis is a complex heteropoly sugar, with a sulfate content of about 6%. It is primarily composed of D-mannose, D-glucose, D-galactose, L-rhamnose, and glucuronic acid, among others [15]. These components make up approximately 14% to 16% of the dry weight of Spirulina. Additionally, it contains small amounts of xylose, arabinose, galactose, ribose, fucose, galacturonic acid, and other monosaccharides. Spirulina polysaccharides have the ability to balance the antioxidant system and eliminate free radicals [16]. As a result, they can inhibit oxidative damage in the body, increase serum insulin levels, enhance the activity of superoxide dismutase (SOD), and reduce the levels of MDA, thereby achieving the desired effect of lowering blood sugar [17].

Function of bioactive substances in Spirulina

Spirulina is a nutrient-rich algae that serves as a natural superfood and synthesizes numerous biologically active secondary metabolites during its growth. These secondary metabolites exhibit various effects, including antioxidation, anti-inflammatory properties, immune regulation, and anti-tumor activity. As a result, they hold significant potential for applications in medicine, healthcare products, cosmetics, and other industries. Table 1 presents the identified secondary metabolites of spirulina thus far.Spirulina, a green algae known for its remarkably high protein content, is regarded as a promising “cell factory” due to its potential as a nutrient source for organisms and as a producer of bioactive peptides with therapeutic properties. In recent years, numerous studies have demonstrated that certain peptides released through hydrolysis exhibit significant biological activities, including blood pressure reduction, antioxidation, anti-inflammation, anti-cancer effects, and immune regulation. The biological activity and mechanisms of spirulina proteolytic peptides have been extensively documented in various literature sources, as outlined in Table 2.

Antioxidant activity

Oxidative stress refers to an imbalance between oxidation and anti-oxidation within the body. This condition arises from the excessive accumulation of reactive oxygen species, including superoxide anion (·O2-), hydrogen peroxide (H2O2), hydroxyl group (-OH), and others. Cell peroxidation leads to the formation of malondialdehyde (MDA), which alters cell membrane permeability and causes cellular damage. Oxidative stress serves as a primary contributor to metabolic disorders, cardiovascular diseases, inflammation, liver injury, and various other ailments. Many chronic and age-related diseases, such as hypertension, hyperlipidemia, diabetes, Parkinson’s disease, and Alzheimer’s disease, stem from

Laboratory cultivation

Eight major environmental factors influence the productivity of Spirulina: luminosity (photo- period 12/12,4 luxes), temperature (30 °C), inoculation size, stirring speed, dissolved solids (10–60 g/liter), pH (8.5–10.5), water quality, and macro and micronutrient presence (C, N, P, K, S, Mg, Na, Cl, Ca and Fe, Zn, Cu, Ni, Co, Se).

High yield

With around 60 percent protein content, Spirulina's rapid growth means it yields 20 times more protein per unit area than soybeans, 40 times more than corn, and over 200 times more than beef.

 Small-scale commercial production of Spirulina

Spirulina cultivation has a number of advantages over traditional agriculture:

Efficient source of energy

Spirulina requires less energy input per kilo than soya, corn or beef, including solar and generated energy. Its energy efficiency (food energy output/kg/energy input/kg) is five times higher than soya, two times higher than corn, and over 100 times higher than grain-fed beef. The small-scale production of Spirulina is considered as a potential income-generating activity for households or village collectives. Spirulina might be also dried and processed for local consumption, especially where poor dietary regimes need to be supplemented. In addition, the extensive or semi intensive production of Spirulina for animal or aquatic feeds might be conducted for small-scale farming and aquaculture.

Spirulina indeed lends itself to simple technology

Cultivation may be carried out in unlined ditches through which flow is low (e.g. 10 cm/second). Stirring may be provided by a simple device driven by wind energy or harnessed to humans. Harvesting mat be readily performed using some suitable cloth, and the biomass dehydrates in the sun. The quality of the Spirulina product obtained in this fashion would not be as high as what is attained in clean cultures, but product could serve well as animal feed. In Bangladesh, Spirulina was produced through a pilot project using paddle-wheel under transparent shade in the campus of BCSIR (Bangladesh Council for Scientific and Industrial Research) in 1980s. Later BCSIR established a system for the rural culture of Spirulina. of Tamil Nadu. For instance, mud pot Spirulina production uses a medium consisting of biogas slurry, 2–3 g of sea salt or chemical medium (potassium dihydrogen phosphate, cooking soda and sodium chloride) and pure Spirulina culture. Production of Spirulina in organic nutrients including waste effluents may contest with the cost effectiveness. In Nigeria waste water is used for cultivation of Chlorella and Spirulina. Alternate use of organic nutrient source, waste water effluent available in rural source The fertilizer factory waste on an average contained phosphate-P (107–187 ppm), nitrate-N (3.0–4.0 ppm), sulfate SO4-2 (146–150 ppm), had a pH of 7.4–8.5 and electric conductivity of 700–2457 ?mhos/cm. This physico-chemical status of fertilizer factory waste is suitable for the growth of Chlorella and Spirulina. Approximately, 11.0 percent (w/w dry matter) as no. of Spirulina was obtained when cultured in 50:50 mixture of effluent and filtered sea water (pH 8.30) after 21 days.

Commercial and mass cultivation

The main commercial large-scale culture of microalgae started in the early 1960s in Japan with the culture of Chlorella, followed by Spirulina in the early 1970s at Lake Texcoco, Mexico.Spirulina is produced in at least 22 countries: Benin, Brazil, Burkina Faso, Chad, Chile, China, Costa Rica, Côte d'Ivoire, Cuba, Ecuador, France, India, Madagascar, Mexico, Myanmar, Peru, Israel, Spain, Thailand, Togo, United States of America and Viet Nam. The total industrial production of Spirulina is about 3000 tons a year.

The main Pigments found in Spirulina are

Chlorophyll

The most visible pigment in Spirulina is chlorophyll. Chlorophyll is sometimes called green blood because of its similarity to the hemoglobin molecule found in human blood cells. Chlorophyll is known as the cleansing and detoxifying phytonutrients, increases peristaltic action and thus relieves constipation. It also normalizes the secretion of digestive acids. In addition, Spirulina soothes the inflammation and reduces the excess pepsin secretion associated with gastric ulcers. It has antiseptic qualities as it reduces swelling and promotes granulation- a process that regenerates new tissue over injuries, promotes regeneration of damaged cells and improves overall efficiency of cardiac work.

Carotenoids

Spirulina is the richest food source of beta-carotene which is a Vitamin A precursor. It has 21 times more beta carotene than raw carrots and with a spectrum of 10 mixed carotenoids, about half are orange carotene. These are alpha, beta and gamma. These components are half xanthophylls which work synergistically at different sites in our body to enhance healthy eyes and vision and antioxidant protection.

Phycocyanin

It is a brilliant blue polypeptide which is a source of biliverdin (a green pigment excreted in bile) which is most potent intra-cellular antioxidants and related to human pigment bilirubin and stem cells. Its components are important to healthy liver function and digestion of amino acids.

Porphyrin

Porphyrin is a red compound that forms the active nucleus of hemoglobin. It is essential for the formation of red blood cells. It is used as a chelator for heavy metal toxicity and circulation problems. Porphyrins have the ability to bind divalent metal ions due to the nitrogen atoms of the tetrapyrrole nucleus. The central ion in chlorophyll is magnesium, which is freed from chlorophyll under acidic conditions permitting other metals to bind in its place. Toxic metals, such as mercury, lead and arsenic, are complexed first then excess amounts of other divalent metals, such as calcium, can be complexed by porphyrins. By increasing the porphyrin content, the heavy metal binding capability is also increased, providing clinicians with a natural, effective “chelating” tool.

Enzymes

Spirulina contains a number of enzymes. One of the most significant enzymes is superoxide dismutase (SOD), which is important in quenching free radicals and in retarding aging. This essential enzyme is crucial to the body’s ability to assimilate amino acids. Without SOD's presence in the body, we are unable to create the 10,000’s of long, complex chains of amino acids known as proteins. In fact, Spirulina is so high in enzyme activity that even after being dried (at 160 ?C) it will often start growing again if placed in the right medium, temperature andsunlight. Spirulina has been scientifically demonstrated to increase reproduction of lacto-bacilli (bacteria that digests our food). It contains over 2000 different enzymes.As early as 1949, Spoehr and Milner (1949) suggested that the mass culture of algae would help to overcome global protein shortages.

Ironically, in spite of the lamentably low per capita protein supplies in many parts of the world, mass cultivation of algae has received only casual interest. The United Nations Environmental Programme (UNEP) is emphasizing nitrogen fixation and nutrient recycling through a programme that will establish microbiological centers (MIRCENS), and it is hoped that this will stimulate interest in micro-algae technology as a component of an integrated recycling system for rural communities [14].oxidative stress. Spirulina, due to its abundance of bioactive ingredients like phycocyanin, carotenoids, and algal polysaccharides, can enhance the body’s antioxidant capacity [72, 73]. It aids in preventing lipid peroxidation, DNA damage, and the removal of free radicals. At present, numerous studies have focused on the antioxidant effect of spirulina. Spirulina exhibits robust antioxidant enzyme activity, which effectively inhibits intracellular lipid peroxidation and DNA damage, while also efficiently eliminating free radicals [74]. Furthermore, spirulina demonstrates specific protective effects on the nervous system and kidneys of animals by reducing oxidative stress [75]. Given its high antioxidant activity, spirulina is considered a promising agent for the prevention and treatment of cardiovascular diseases [76, 77]. Despite limited clinical studies in humans, spirulina's potent antioxidant capacity enables it to effectively treat chronic obstructive pulmonary disease and skeletal muscle damage caused by intense exercise [78, 79]. However, there are various methods available for detecting antioxidant systems, with the DPPH free radical clearance assay being the most commonly used. Ding Xiaomei et al. extracted polysaccharide from Spirulina platensis using conditions of pH = 8, temperature of 90°C, solid-liquid ratio of 1:40, and an extraction time of 2 hours [80]. The resulting IC50 value of 0.463 g/L confirmed the DPPH free radical scavenging ability. Yu Chengming et al. conducted a study that demonstrated a significant scavenging effect of DPPH free radicals when the phycocyanin concentration was 8 g/L, reaching a scavenging rate of 89.95%, which was superior to VC and indicated the excellent antioxidant capacity of phycocyanin [81]. Zhang Yifang et al. purified spirulina algal protein and through antioxidant experiments, proved its superior scavenging ability compared to VC [82]. The results highlighted the strong antioxidant ability of Spirulina spirulina’s algin. Li Ling et al. conducted in vitro experiments to determine the scavenging effects of polysaccharides from Spirulina and Spirulina on -OH and ·O2- [83]. They also used a lipid peroxidation model induced by FeSO4 and thiobarbituric acid spectrophotometry to study the anti-lipid peroxidation and oxidative damage properties of these polysaccharides. The findings revealed that a concentration of 0.15 mg·mL-1 of polysaccharides from Spirulina platensis effectively removed oxygen free radicals and inhibited DNA oxidation and oxidative damage.

The inflammatory response is a defensive reaction that occurs following tissue injury or the invasion of foreign substances. It serves as the foundation for the development of numerous diseases. Chronic inflammation, often referred to as the “precursor” of cancer, is found to be present in 25% of tumors during their formation and progression, according to epidemiological investigations. Prolonged inflammation poses a threat to cardiovascular health, leading to conditions such as atherosclerosis and thrombosis, ultimately resulting in heart disease [84]. Additionally, it damages nerve tissue, increasing the risk of Alzheimer's disease. Severe inflammatory reactions can spread from localized inflammatory sites, causing infections that may progress to sepsis and eventually lead to death. Currently, commonly used clinical anti-inflammatory drugs often come with significant side effects, including damage to human tissues and organs, as well as immunosuppression. Therefore, the development of effective anti-inflammatory drugs with minimal toxic side effects is of utmost importance [85]. Spirulina is abundant in bioactive substances such as phycocyanin, spirulina polysaccharide, eicosapentaenoic acid, SOD, vitamins, and flavonoids. It has become a prominent research focus in the medical field worldwide. The therapeutic potential of spirulina proteolytic peptides in treating inflammation and related diseases has been extensively reported. Peptides derived from macrospirulina, such as LDAVNR, MMLDF, and phycocyanin, have demonstrated anti-inflammatory effects in vitro or in animal models [86]. Phycocyanin peptides exhibit diverse anti-inflammatory effects, including scavenging various oxygen free radicals, inhibiting lipid peroxidation, suppressing amino acid metabolism, inhibiting histamine release in mast cells, and reducing TNF-? release [87–90]. LEDON et al. investigated the anti-inflammatory response of phycocyanin, an extract derived from spirulina, and observed changes in the concentration of prostaglandin E2 (PGE2) and the activity of phospholipase A2 (PLA2) in the presence of phycocyanin [91]. The results demonstrated that phycocyanin exhibited a certain degree of anti-inflammatory activity due to its inhibitory effect on PGE2 production and PLA2 activity. Guzman S et al. discovered that extracts of two crude polysaccharides extracted from spirulina exhibited superior anti-inflammatory activity compared to indomethacin [92]. Matsui MS et al. conducted in vitro tests and found that polysaccharide from Spirulina algina could inhibit the formation of erythema caused by strong stimulation [93]. In vitro experiments revealed that the polysaccharide could inhibit the aggregation and adhesion of haemophilic lymphocytes. Therefore, it is considered a topical anti-inflammatory drug. Chen Zhongwei et al. established an inflammation model in rats by inducing ear swelling using xylene [94]. Dexamethasone was used as a control, and ear swelling in mice served as an experimental indicator. The results showed that the ear swelling inhibition rate of the 0.3% spirulina group was better than that of the positive control drugs, and dexamethasone could cause atrophy of the liver, spleen, and thymus in rats. Spirulina exhibited a better anti-inflammatory effect than dexamethasone and had no adverse effects on liver, kidney, thymus, or spleen indices.

Hypoglycemic activity

Under normal circumstances, the blood sugar level in the human body is maintained at a dynamic balance between 80–120 mg/dL. Hyperglycemia can lead to various chronic complications, including cerebral infarction, myocardial infarction, blindness, kidney failure, and diabetes. Compared to conventional hypoglycemic drugs, spirulina, as a natural plant, has a better hypoglycemic effect and lower toxicity [95]. Researchers have discovered that spirulina primarily affects glucose glycogen, mainly by promoting liver glycogen synthesis or inhibiting its degradation. Through the observation of spirulina’s hypoglycemic effect on diabetic rats, Hozayen WG et al. found that spirulina can inhibit hexokinase activity in liver cells, enhance glucose-6-phosphatase activity in muscles, and reduce glucose absorption in the intestine [96]. This improves insulin's hypoglycemic activity and reduces liver glycogen synthesis, promoting glucose utilization by peripheral tissues. OU et al. studied the effect of phycocyanin in spirulina on diabetes induced by tetrafluoracil and discussed its related molecular mechanism [97]. It was demonstrated that phycocyanin may activate the insulin signaling pathway and protein kinase in the pancreas, liver, and pancreas, promoting liver glycogen degradation and reducing blood glucose levels. Setyaningsih et al. measured the anti-hyperglycemic activity of rats by feeding them biological substances containing spirulina and phycocyanin [98]. The results showed that these substances reduced blood sugar levels in mice. Qi Qinghua et al. used hydrochloric acid precipitation technology to separate and purify polysaccharides and proteins from spirulina [99]. They found that the isolated polysaccharide from Spirulina had a significant effect on hyperglycemia symptoms in diabetic mice induced by alloxouracil, suggesting its potential as a new type of functional food. In addition, for sprinters, spirulina polysaccharides can be appropriately consumed to reduce blood sugar and blood lipids, improve the body’s antioxidant capacity, and enhance its anti-inflammatory capacity, thereby reducing exercise fatigue. The results have demonstrated that the administration of polysaccharide derived from spirulina platensis significantly improves hyperglycemia in rats, effectively counteracts liver glycogenolysis caused by adrenaline, and inhibits glucose absorption in the intestines of mice. Moreover, spirulina polysaccharides have been found to significantly alleviate hyperglycemia symptoms in mice with alloxouracil-induced diabetes and elevate their antioxidant levels. It is crucial for sprinters to closely monitor their blood sugar and blood lipid levels. Based on the analysis of experimental findings, polysaccharide from Spirulina algina can enhance the body’s sugar absorption, increase insulin sensitivity, and consequently reduce the rate of glucose absorption in muscle and adipose tissue. Additionally, polysaccharide from Spirulina platensis can regulate serum fat composition, decrease the expression of sterol regulatory element binding protein in liver tissue, and promote the synthesis of damaged liver mitochondria, thereby effectively enhancing cell regeneration and exerting an anti-fatigue effect.

Hypotensive activity

Hypertension is a systemic condition characterized by elevated arterial pressure and accompanied by functional or organic changes in the heart, blood vessels, brain, and kidneys, all of which are caused by persistent high blood pressure. The most commonly used synthetic antihypertensive drugs, such as captopril, enalapril, acapril, and Lisinopril, primarily work by inhibiting the angiotensin-converting enzyme (ACE). Inhibiting ACE leads to a decrease in angiotensin II and an increase in bradykinin, a vasodilator, which ultimately lowers blood pressure. However, while these synthetic drugs effectively lower blood pressure, they also come with certain adverse reactions, such as dry cough, taste disturbance, rash, and so on [100, 101]. Therefore, the development of safe and effective antihypertensive drugs holds great significance for the prevention and treatment of hypertension. Blood pressure-lowering peptides derived from dietary proteins are considered safer alternatives to synthetic antihypertensive drugs. For instance, the antihypertensive effect of active peptides from seaweed may be attributed to the inhibition of ACE and renin. The renin-angiotensin system plays a crucial role in regulating blood pressure. One mechanism involves inhibiting angiotensin I, which is produced from angiotensinogen, by using renin. The other mechanism involves competitively binding the active site of ACE to prevent the conversion of angiotensin I to angiotensin II, thereby inhibiting kinin hydrolysis and preventing vasoconstriction [102]. ROJAS V et al. demonstrated that active peptides with a molecular weight less than 2 ku exhibited the highest ACE inhibitory activity [103]. Liu Lichuang et al. found that pepsin hydrolysate, trypsin hydrolysate, and a complex hydrolysate of spirulina protein significantly inhibited the increase in blood pressure in essential hypertensive rats (SHR) [104]. Additionally, trypsin and the complex enzyme hydrolysate showed promising therapeutic effects on hypertension. However, the administration of spirulina protein alone did not have a significant impact on SHR hypertension, indicating that the peptides obtained under the three hydrolysis conditions had notable antihypertensive effects.

Anticancer activity

The progression of cancer is a gradual process, making it suitable for the utilization of natural, synthetic, or biological substances to reverse, inhibit, or prevent tumor development and their transformation into malignant cancers, as well as to prevent the occurrence of invasive or metastatic diseases. Phycocyanin, an essential component of spirulina, is water-soluble, non-toxic, and exhibits a certain level of stability. It has been extensively studied and applied in various research studies. Bobbili et al. and Fan Min discovered that phycocyanin can eliminate free radicals and induce apoptosis in AK-5 tumor cells and human cervical cancer Hela cells, respectively [105, 106]. Additionally, it has been observed that polysaccharide derived from Spirulina platensis can inhibit the growth of S180 transplanted tumors in mice, delay the cell division cycle of tumor cells, and induce apoptosis [107, 108]. Furthermore, studies have demonstrated that high concentrations of phycocyanin can induce apoptosis in lung adenocarcinoma cells [109]. MAHMOUD et al. conducted research that showed spirulina to have significant tumor regression effects, improved survival rates, inhibition of A-fetoprotein tumor markers, improved liver biomarkers, and reduced hepatoma pathology in advanced hepatocellular carcinoma [110]. These findings suggest that spirulina holds promise as a potential treatment for hepatocellular carcinoma.

Immune regulation

The occurrence and development of diabetes, senile diseases, and malignant tumors are closely related to the immune disorder of the body. With the in-depth study of the immune mechanism and biological effect of spirulina, the application of spirulina in the prevention of immune disorder diseases has a promising future. Spirulina contains various active ingredients that can enhance the body’s immune function, such as carotenoids, phycocyanin, spirulina polysaccharides, and gamma-linolenic acid, which can enhance immune function [111, 112]. Its mechanism primarily involves enhancing the proliferation of bone marrow cells and promoting the formation of immune effector cells like macrophages, T cells, and B cells. Additionally, phycocyanin can promote phytohemagglutinin to stimulate lymphocyte transformation and improve lymphocyte activity [113, 114]. Lv Xiaohua et al. reported that polysaccharide from Spirulina algina can enhance the proliferation ability of peripheral blood monocytes in patients with chronic hepatitis B and produce immunomodulatory effects [115]. According to the study conducted by Xu Jiaohong et al., polysaccharide from Spirulina platensis can significantly increase the number of antibody-producing cells and the activity of NK cells [116]. The results suggest that polysaccharide from Spirulina platensis can enhance the humoral immunity and NK cell activity of mice. Phycocyanin can enhance immune function by primarily enhancing the proliferation of bone marrow cells and promoting the formation of immune effector cells like macrophages, T cells, and B cells. Additionally, phycocyanin can promote phytohemagglutinin to stimulate lymphocyte transformation and improve lymphocyte activity [117].

Lose Weight

Algae is a beneficial option for weight loss due to its low fat, calorie, and fiber content. In the ancient “food therapy Materia Medica”, kelp was noted to “reduce Qi and help slim down”. Algae is rich in dietary fiber, which can reduce the intake of energy in the body, leading to a decline in the digestion and absorption of nutrients in the intestines. Additionally, it promotes gastrointestinal peristalsis, eliminating harmful substances from the body and maintaining intestinal health [118]. Spirulina is abundant in phenylamino acids, which can influence the brain to control appetite, balance cravings, effectively regulate body fat content, and alleviate hunger caused by other weight loss methods. Spirulina can reduce the infiltration of macrophages into visceral fat, prevent the accumulation of liver fat, decrease oxidative stress, improve insulin sensitivity, and promote satiety. Research has demonstrated that moderate supplementation of spirulina can enhance apolipoprotein A1 levels and reduce apolipoprotein B, aiding in weight loss and lowering Body Mass Index. Spirulina achieves weight loss by reducing the permeability of macrophages into visceral fat and preventing the accumulation of liver fat and oxidative stress [119].

Development, utilization and application prospect of spirulina

Application in dairy products

Phycocyanin, a water-soluble protein, has a positive impact on reducing water solubility and increasing the firmness of yogurt. When spirulina powder is added during the yogurt-making process, it results in a curd-like and firm yogurt with the distinct aroma of spirulina and frankincense, and a vibrant green color [120]. To make cheese, it is recommended to prepare the soft cheese beforehand, and then add 1% spirulina powder while freezing and adding salt. Stir the mixture and store it in the refrigerator. Spirulina can enhance the protein and beta-carotene content of soft cheese, reduce moisture, and prolong its shelf life.

The application in flour products

Algae can be ground into powder or made into a paste, serving as a raw material in food production to enhance nutritional value. Additionally, algae possesses strong water absorption, gelling, thickening, and film-forming abilities, which can improve the processing quality of flour-based products. In a study conducted by Mostolizadeh et al., 0.25% to 1% spirulina powder was added to pasta, resulting in a significant increase in essential amino acids and unsaturated fatty acids in the food [121]. Pasta with 0.25% spirulina powder exhibited favorable microbial characteristics and nutritional value. It enhances satiety and is considered a sustainable food option.

Application in animal feed

Incorporating spirulina into animal feed can enhance the nutritional value of food, meeting the dietary requirements of humans. Spirulina shows potential as a protein source in poultry, pork production, and aquaculture. According to the study conducted by ANDREWS et al., the addition of 1% to 4% spirulina powder to the diet of Labeo rohita resulted in a significant increase in the total number of red blood cells, hemoglobin, and white blood cells [122]. Furthermore, serum total protein, albumin, globulin, and respiratory burst activity were also significantly elevated. A significant number of application studies on various aquaculture animals have demonstrated that spirulina powder not only showcases its high nutritional value but also possesses a range of functional effects on aquatic animals. Spirulina’s phycocyanin, polysaccharide, and beta-carotene content can enhance the immunity of cultured animals, while the polysaccharides found in microalgae can bolster the immune response, making it suitable for aquatic feed. This, in turn, aids in enhancing the disease resistance of farmed animals. Currently, a significant amount of spirulina powder has been utilized in food or aquatic feed in foreign countries. However, the application of spirulina powder in aquatic feed in China is still in a relatively early stage, and the potential of spirulina resources has not been fully realized. Therefore, it is necessary to conduct more comprehensive and in-depth systematic research and enhance the dissemination of research results. This will enable aquaculture operators to gain a better understanding of the superiority of spirulina.

The application of spirulina in medicine

Manufacturing drug carriers. Spirulina, being a natural porous carrier, has the potential to be utilized in the production of drug carriers [123]. Its cell surface contains a significant amount of cell wall proteins, polysaccharides, amino acids, fatty acids, and other substances, which contribute to its strong drug adsorption capacity. By altering parameters such as particle size, surface properties, and pore size, the drug carrier made from spirulina can effectively control the dissolution rate and release behavior of the drug [124]. Furthermore, as a drug carrier, spirulina can stabilize the biochemical and chemical properties of drugs, prolong their residence time in the body, and enhance the effectiveness of drug therapy.

For liver disease treatment. Spirulina is abundant in nutrients such as lutein and beta-carotene, which possess antioxidant and anti-inflammatory properties. These nutrients can mitigate the detrimental effects of oxidative damage and inflammation on liver cells, thus safeguarding their well-being [125]. Additionally, the diverse array of nutrients and bioactive substances found in spirulina can help prevent liver complications like hepatitis and cirrhosis, promoting overall liver health [126]. Studies have indicated that polysaccharides extracted from spirulina exhibit inhibitory effects on the replication of the hepatitis C virus, suggesting their potential as a treatment for hepatitis C.

The application of spirulina in cosmetics

Spirulina is enriched with a variety of antioxidant substances, including carotenoids and vitamin E, which effectively combat free radicals, safeguard the skin against environmental pollution and oxidative damage, and possess anti-aging properties. Furthermore, spirulina is abundant in natural moisturizing factors and polysaccharides, which aid in maintaining skin moisture and promoting a soft and supple complexion. The peptides present in spirulina stimulate collagen synthesis, resulting in firmer and more elastic skin. Additionally, the sulfides found in spirulina can alleviate skin  inflammation  and  discomfort,  exhibiting  certain anti-inflammatory effects. Moreover, spirulina contains natural whitening ingredients like lutein and carotenoids, which effectively inhibit melanin synthesis, reducing the appearance of dark spots and dullness [127]. The moisturizing rate within 24 hours was nearly equivalent to that of the body lotion containing 2% polysaccharide mass fraction and 5% glycerol solution. The SPF of the moisturizing lotion, with a polysaccharide content ranging from 0.3% to 1.0%, was found to be 10 to 15 at the wavelength of 280 to 320 nm, indicating its effectiveness in providing protection against UV rays.

Application of spirulina in health care products

Enhance immunity. Spirulina comprises a diverse range of nutrients and antioxidants that can aid in boosting the body's immune system, strengthening its resilience, and safeguarding against infections and diseases.

Regulating blood lipids and blood sugar. The assortment of nutrients found in spirulina has the potential to lower blood lipids and blood sugar levels, thereby acting as a preventive measure against chronic conditions like cardiovascular disease and diabetes.

Improve the digestive system. Spirulina is abundant in dietary fiber, probiotics, and other substances that can stimulate intestinal motility, facilitate regular bowel movements, enhance abdominal comfort, and optimize the functioning of the digestive system.

Anti-fatigue. Spirulina encompasses a diverse array of vitamins and antioxidants that can supply the body with essential nutrients and energy, thereby assisting in the reduction of fatigue and stress levels. Beauty. Spirulina comprises a range of beauty-enhancing nutrients, including lutein and beta-carotene, that contribute to the promotion of healthy skin, hair, and nails, ultimately enhancing their appearance and maintaining their overall well-being. In general, spirulina has a range of effects in healthcare products, which can provide comprehensive protection and maintenance for people’s health.

Spirulina can thrive in intense light and high-temperature environments, exhibiting a high growth rate, abundant oil yield, and remarkable adaptability. As a result, it is widely recognized as a promising biomass energy source.

Spirulina in the application of biofuels

Biodiesel production. Spirulina contains a significant amount of oil, with approximately 25 grams of oil extractable from every 100 grams of spirulina [128]. These oils are abundant in unsaturated fatty acids, which can be extracted and transformed into biodiesel for energy, making them promising raw materials for biodiesel production.

Production of biogas. When spirulina undergoes photosynthesis in the presence of light, it generates a substantial quantity of oxygen and hydrogen [129]. These gases can be harnessed and utilized as clean energy sources in various devices, including fuel cells. Additionally, under anaerobic conditions, spirulina can be converted into biogas, serving as a viable alternative to natural gas [130].

Reduce greenhouse gas emissions. Spirulina is a highly efficient absorber of carbon dioxide. It possesses the capability to utilize carbon sources for growth and effectively sequester a substantial amount of carbon for the production of biodiesel and biogas. These fuels exhibit lower carbon emissions and contribute to the reduction of environmental pollution and global climate change. In summary, spirulina holds a broad range of potential applications in biofuels and can effectively address energy and environmental challenges (Figure 2).

Prospect

As a 21st century “superfood”, Spirulina is widely used as a natural food supplement worldwide. It has a long history of being safe and non-toxic to consume. It is a staple in the daily diets of African and Native American populations. Spirulina is abundant in nutrients and is highly safe. It is a protein source with low fat, low calories, and no cholesterol, which can enhance human immunity, combat viruses and oxidation, and aid in disease treatment. It is highly effective for human health and holds significant value in the fields of health food and beauty products. However, the extraction yield is generally low, limiting the further development of spirulina products and failing to fully meet consumer demand. Improving the extraction method, reducing production costs, increasing the extraction rate of spirulina’s active substances, and enhancing clinical trials are the focal points and directions of future spirulina research. With the advancement and maturity of genetic engineering technology, applying genetic engineering to modify, breed, and mutate spirulina holds the potential to create greater benefits for humanity, warranting further investigation. Currently, the mechanism of spirulina and its applications in other fields are being studied both domestically and internationally. Spirulina possesses strong antioxidant capabilities, making it suitable not only for the healthcare industry but also for the preservation of fruits, vegetables, and aquatic products. Its market potential is immeasurable. However, it is important to note that while spirulina and its products are gaining opularity among the public, it is necessary to fully understand the potential risks of spirulina as a nutritional supplement. This includes assessing whether it causes sensitization or has antagonistic effects when combined with certain substances. Relevant research institutions and scholars should conduct risk assessments on spirulina. Considering its safety, nutritional value, and functional characteristics, spirulina and its active substances have a promising future in the research and development of functional food and preservatives. They are expected to become a new star in the healthcare product and preservative industries, ultimately serving human health more effectively.

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