Freshwater Microalgae as Promising Food Sources: Nutritional and Functional Properties

Abstract

A number of researchers have predicted that the current food crisis is predicted to worsen in 2050. The prediction of this crisis is aligned with climate change causing increases in some basic foodstuff prices. Therefore, everyone should prepare to consume alternative foods at an early stage. Alternative foods have been widely developed, one of which involves microalgae. However, the type of microalgae produced by some countries on a large scale consists of only oceanic/seawater microalgae. This will have an impact on and hinder development in countries that do not have these resources. Therefore, it is necessary to explore the use of microalgae derived from freshwater. Unfortunately, freshwater microalgae are still rarely investigated for use as alternative foods. However, there is considerable potential to utilize freshwater microalgae, and these algae are very abundant and diverse. In terms of nutritional properties, compared to oceanic / seawater microalgae, freshwater microalgae contain nearly the same protein and amino acids, lipids and fatty acids, carbohydrates, and vitamins. There are even more species whose composition is similar to those currently consumed foods, such as beef, chicken, beans, eggs, and corn. In addition to dietary properties, freshwater microalgae also have functional properties, due to the presence of pigments, sterols, fatty acids, and polyphenols. Given the potential of freshwater microalgae, these aquatic resources need to be developed for potential use as future food resources.

Keywords: Bioactive, Food, Freshwater, Functional properties, Microalgae, Nutrition, Underexplored.

1. INTRODUCTION

Food security is a topic that continues to be a topic of interest in all countries and has been linked to several factors, such as growing populations and rising food prices [1]. According to the Global Network Against Food Crises, the severity of the food crisis worsened in 2020 due to conflict, the economic impact of coronavirus disease (COVID-19) and extreme weather. In 2021, the world will experience a food crisis [2]. The effects of climate change, such as increased temperature, decreased water availability, and increased carbon dioxide, have decreased crop productivity. These phenomena will worsen the condition of areas where people are already vulnerable to hunger and malnutrition [3]. Regions in which these effects are especially concerning include sub-Saharan Africa and South Asia. It is estimated that countries will experience an average crop decline of up to 8% by 2050. The harvest is expected to change by -17% (wheat), -5% (corn), -15% (sorghum) and -10% (millet) in Africa and by -16% (corn) and -11% (sorghum) in South Asia [4]. The food crisis will become dangerous if every country does not provide other alternatives to meet food demands. Therefore, new potential food sources are needed to meet nutritional requirements.

Microalgae can be used as alternative foods due to their nutritional contents. In China, people have long used microalgae as food sources. Commonly used microalgae include Arthrospira, Nostoc, and Aphanizomenon. More than 2000 years ago, algae were already used as food [5]. It is also known that the Aztecs consumed Spirulina in the 14-16th centuries. The production of microalgae as food stocks began to be encouraged in the Second World War, during which time Japan, America, and Germany were facing a food crisis [6].

Some countries have begun expanding and producing large-scale microalgae as health supplements, pharmaceuticals, and biofuels. Biofuels from microalgae are environmentally friendly and nontoxic. Carbohydrate-rich microalgae such as Chlamydomonas reinhardtii and Chlorella vulgaris have been widely used for biofuel production [7]. Developing countries such as those in Africa with a coastline stretching for 1420 km have succeeded in increasing the production of seawater microalgae from 0.08 million tons to 0.14 million tons. In addition, microalgae such as Spirulina have been used as foods and supplements [8]. In addition to Africa, Europe already has countries where algae (67%) and microalgae (33%) are produced. Spirulina producers include 23 countries, with the most significant biomass produced in Norway, France, and Ireland [9]. However, many countries develop only seawater microalgae, so development is limited if these countries are not adjacent to seawater. Therefore, the freshwater microalga is an attractive solution to address this issue.

Microalgae are photosynthetic microorganisms that utilize carbon dioxide and sunlight to form biomass and produce approximately 50% of the oxygen in the atmosphere. There are four types of microalgae, namely, Bacillariophyceae (diatoms), Chlorophyceae (green algae), Chrysophyceae (golden algae), and Cyanophyceae (blue algae). Although many countries in the Tropics have a high diversity of microalgae, their potential is still underexplored. In many countries, microalgae have been used as biofuel production agents because microalgae can produce high levels of fatty acids and carbohydrates [10-14]. Through the esterification process, microalgal fatty acids can be converted to biodiesel.

Research and discussions related to microalgae are still dominated by their application in wastewater treatment, bioenergy, and the pharmaceutical industry [15-17]. However, microalgae have long been used as foods [18, 19]. This review shows freshwater microalgae's nutritional quality and functional properties and their potential to be developed as food sources to address the global food crisis.

2. POTENTIAL AND DIVERSITY OF FRESHWATER MICROALGAE

The abundance of algal species is estimated to be nearly ten million. In terms of classification of algae, they can be broadly assigned to 11 main phyla: Cyanophyta, Chlorophyta, Rhodophyta, Glaucophyta, Euglenophyta, Chlorarachniophyta, Charophyta, Cryptophyta, Haptophyta, Heterokontophyta, and Dinophyta [20].

Several freshwater microalgae have been reported. However, many researchers are only interested in studying their physiology and how they respond to environmental change. As a result, many freshwater microalgal species are still unknown. The classes Zygnematophyceae, Euglenoidea, and Chlorodendrophycea are among the most widely found. Details of the species commonly explored by researchers are listed in Table 1.

According to Matos et al. [21], microalgae are sources of bioactive ingredients and compounds for the most promising new food products. They can increase the nutritional value of food due to their balanced chemical composition. The addition of microalgae to food products is an excellent way to supplement nutrients and biologically active compounds. Chlorella is the most explored genus in terms of the suitability of its species compared to other species as dietary supplements [22-24].

Table 1.
Classification of commonly investigated freshwater microalgae.
No. Class Species
1 Chlorophyceae Scenedesmus obliquus
Chlamydomonas reinhardtii
Haematococcus pluvialis
Monoraphidium spp.
Ankistrodesmus falcatus
Oscillatoria
2 Cyanophyceae Nostoc commune var. sphaeroides
Aphanizomenon flos-aquae
Synechocystis spp.
Anabaena cylindrica
3 Eustigmatophyceae Nannochloropsis limnetica
4. Trebouxiophyceae Chlorella pyrenoidosa
Chlorella vulgaris
Chlorella sorokiniana
Micractinium conductrix
Choricystis minor
Botryococcus braunii
5. Euglenoidea Euglena glaciris
6. Bacillariophyceae Pinnularia spp.
Navicula spp.
Frastulia spp.
Didymosphenia spp.
7. Zygnematophyceae Spirogyra spp.
8. Chlorodendrophyceae Tetraselmis cordiformis

3. NUTRITIONAL PROPERTIES

The use of microalgae as food sources has been known for a long time. Microalgae are considered potential new food sources due to their high nutrients content. The nutrient composition of microalgae varies, and even for the same species, the nutritional content of individual microalgae can differ significantly due to the growth conditions, such as the composition of media and temperature for growth. The main nutritional components are mainly proteins and lipids, as well as vitamins and minerals, all of which are known to have a positive impact on human health [25]. Important macronutrient components (proteins, carbohydrates, and fats) can be found in high proportions. In general, the macro nutritional components of various freshwater microalgae are summarized in Table 2.

The nutritional value of algal species for a particular organism depends on the size of the algal cells, their digestibility, their production of toxic compounds, and their biochemical composition. Although there are striking differences in the composition of classes and microalgal species, proteins are always the primary organic components, usually followed by lipids and carbohydrates, regarding the percentage of dry biomass weight. Protein, fat and carbohydrate levels range from 12-35%, 7.2-23%, and 4.6-23%, respectively [36].

3.1. Proteins and Amino Acids

Protein is an essential macronutrient in food. Microalgae are considered a viable source of protein. Some freshwater microalgal species contain proteins similar to those of traditional protein sources, such as beef, eggs, chicken, corn, and beans. Microalgae protein is high and has a high nutritional value [37]. However, the quality of proteins varies, generally depending on the availability of essential amino acids in the proteins. Familiar sources of essential amino acids are eggs, poultry meat, red meat, milk, soy, and fish. These sources have complete suites of amino acids. However, there are consumption constraints for vegetarians. Vegetarians generally consume plant proteins with lower nutritional value due to the lack of essential amino acids.

On the other hand, microalgae are excellent sources of essential amino acids. Approximately 70% of the mass weight of Chlorella spp. reportedly comprises protein [37]. According to WHO / FAO / UNU recommendations, microalgae such as Chlorella spp. have balanced contents of essential amino acids needed for human consumption [38]. Some freshwater microalgal species have higher protein contents than traditional food sources (Table 2). For example, A. flos-aquae species have 62% more protein than other microalgal species [32]. The freshwater microalga with the lowest protein content is E. gracilis—29% [27]. The protein content in A. flos-aquae is higher than the protein content in beef (43%) [39]. Although E. gracilis has the lowest protein content among the microalgal species, the protein content of E. gracilis (with an average of 26%) is higher than the protein content in nuts [40].

Differences in protein values among microalgae are caused by several factors, such as temperature, light intensity, and nutrient composition in culture media [41, 42]. Temperature and light are considered the most crucial factors because microalgae are cultivated outdoors to obtain direct sunlight exposure, so there are also variations in daily and seasonal temperatures [43, 44]. Furthermore, microalgae grow in the temperature range of 15-35 °C [45]. Occasionally, the use of high temperatures induces protein degradation, disrupts enzyme regulation, and breaks down protein structure, resulting in decreased protein content [46].

As mentioned, temperature and light intensity influence the protein content of microalgae. For example, Baiee and Salman [47] showed that high light intensity increases the protein content in C. vulgaris. On the other hand, in Chlorella spp., the high intensity of light causes a decrease in protein content. According to He et al. [48] the need for light intensity on species varies. In C. vulgaris, fluorescent lamps are used during the day (40, 200 and 400 μmol photons m-2 s-1) without a dark period, while in Chlorella spp., fluorescent lamps with different light intensities are used (125, 268, and 300 μmol photons m-2s-1), and the photoperiod has no effect.

The composition of nutrients in microalgae media also plays a vital role. Since nitrogen is a building block of proteins, nitrogen availability significantly influences protein content [38]. In addition, nitrogen concentration is related to the temperature of the treatment. Protein content increases under high nitrogen concentrations and low temperatures. The highest protein content (138 mg.g-1) was found in cultures with a high nitrogen concentration (60 mg L-1 N-NO3). The highest nitrogen concentration was 45% higher than the lowest nitrogen concentration (12 mg.L-1 N-NO3) when both cultures were at 27 °C. At low nitrogen concentrations, the protein content increases with temperature. Regarding high nitrogen concentrations, the protein content decreases as the temperature increases [49].

Microalgae have been identified as potential sources of high-protein foods needed by malnourished people [50]. Microalgae consumption as dietary supplements usually occurs through pills, tablets, powders, or pastes. In recent years, microalga-derived proteins have been incorporated into biscuits, candy, bread, noodles, and beverages [40].

In general, the nutritional value of plant-based protein sources is lower than that of animal protein sources. One of the main factors determining these qualities is that not all proteins contain essential amino acids in adequate amounts (called complete proteins). Amino acids produced by seven freshwater microalgae species have different essential and nonessential amino acids (Table 3). The species with a high average essential amino acid content is N. limnetica; compared with other species, this species contains essential amino acids such as histidine, isoleucine, leucine, methionine, and phenylalanine with higher contents. For example, the leucine content was 9.16% higher than the leucine content in eggs (8.8%) and soybeans (7.7%). In addition, the value of phenylalanine was 5.10% greater than that of eggs (5.8%) and soybeans (5%). The highest lysine content occurs in C. vulgaris, 8.4%, and higher than eggs (5.3%) and soybeans (6.4%).

Table 2.
Macronutrient properties of freshwater microalgae (% of dry matter).
Species Proteins Lipids Carbohydrates Media and Growth Condition References
C. vulgaris 51-58 14-22 12-17.6 - Media: Bold’s Basal Medium (BBM)
- Temperature: 30 ± 1°C
- Light intensity: cool white fluorescent lamps with an intensity of 50 μmol-1 m2 s-1 with 16:8 h photoperiod
- Incubation time: 10 days
Wolker et al. [26]; Ramaraj et al. [27]
C. pyrenoidosa 44 6 27 - Media: BG-11 and EG
- Temperature: 28 ° C
- Light intensity: light intensity of 34 μmol-1 m2 s-1 under continuous light illumination
- Incubation time: 4 days
Yadavalli et al. [28]
E. gracilis 29 10 38 - Media: BG-11 and EG
- Temperature: 28 ° C
- Light intensity: light intensity of 34 μmol-1 m2 s-1 under continuous light illumination
- Incubation time: 4 days
Yadavalli et al. [28]
H. pluvialis 13.78–21.23 8.29–16.17 47.20–64.22 - Media: BG-11, modified BG-11, and medium of Šetlik
- Temperature: 21,5 – 40,5°C
- Light intensity: photon flux density of 2 x 132 μmol-1 m2 s-1
- Incubation time: 4 days
Gacheva et al. [29]
Scenedesmus quadricauda 34.69 0.63 15.99 - Media: BG-11
- Temperature: 21 ± 2°C
- Light intensity: three cool white fluorescent lamps with a combined light intensity of 1.90 Klux on a 12:12 h light: dark cycle.
- Incubation time: 22 days
Arguelles [30]
S. obliquus 30.8-37.7 22-42.6 20–42.6 - Media: Bold’s Basal Medium (BBM) and Bristol’s medium
- Temperature: natural condition (outdoor; day: 34 ± 2,1°C; night: 27± 1,7°C), control condition (in a room 25 ± 1°C)
- Light intensity: natural condition (under shade and based on natural sunlight), control condition (2000)
- Incubation time: 24 hours
Khatoon et al. [31]
Selenastrum bibraianum 38.9–44.7 9.4–38.9 8–38.2 - Media: Bold’s Basal Medium (BBM) and Bristol’s medium
- Temperature: natural condition (outdoor; day: 34 ± 2,1°C; night: 27± 1,7°C), control condition (in a room 25 ± 1°C)
- Light intensity: natural condition (under shade and based on natural sunlight), control condition (2000)
- Incubation time: 24 hours
Khatoon et al. [31]
A. cylindrica 43-56 4-7 25-30 - Media: BG-11
- Temperature: 25 ± 1°C
- Light intensity: under illumination from cool white fluorescent tubes (92.5 µmol photons m2 s-1) with 14:10 hours of light-dark cycle
- Incubation time: 5 days
Becker [32, 33]; Patel et al. [34]
A. flos-aquae 62 3 23 - Media: BG-11
- Temperature: no reported
- Light intensity: no reported
- Incubation time: no reported
Becker [32, 33]
C. reinhardtii 32.7‒48 17.8‒21 15.5‒17 - Media: Modified Bold 6N (MB6N)
- Temperature: 23°C
- Light intensity: 50 µmol photons m2 s-1 (white fluorescent lamps)
- Incubation time: 48-72 hours
Becker [32, 33]; Nakanishi [35]

N. limnetica also has a high content of the nonessential amino acids glutamine, glycine, proline, and cysteine. N. limnetica contains more glycine and proline than eggs and soybeans. H. pluvialis has a higher arginine content than eggs and soybeans do. Chronakis and Madsen [38] explained that edible algae generally present similar patterns of amino acids.

The algae protein has a high content of essential amino acids such as valine, leucine, lysine, and phenylalanine. According to Kay and Barton [54], microalgae generally have low sulfur concentrations, so the amino acid contents of cysteine, methionine, and lysine are low. The concentration of amino acids with methionine and lysine becomes low if the microalgae are processed with heating or in the presence of reducing sugars (the Maillard reaction). Altogether, the average composition of essential amino acids in an algal protein is better than in vegetables.

3.2. Lipids and Fatty Acids

Lipids are indispensable components of cells and are precursors to many important molecules. Hundreds of microalgal strains capable of producing lipids have been reported [55]. Most of them are marine microalgae. Recently, Torres-Tiji et al. [25] reported several freshwater microalgae that accumulate high amounts of lipids, such as Chlorella protothecoides, which comprise up to 70% lipids (dry biomass). According to Ambrozova et al. [56], freshwater microalgae have a higher lipid content than seaweed. Allard and Templier [57] reported that various freshwater and marine microalgae have various lipid contents (1 to 26%). Traditional sources of lipids other than microalgae include fish and seafood. Fish contain a relatively high abundance of omega-3 fatty acids, as fish consume plankton and algae. Algae produce essential long-chain polyunsaturated fatty acids (PUFAs). Several freshwater microalgae along with their lipid content, are listed in Table 2.

Based on the information in Table 2, the microalgal species with the highest lipid content is S. obliquus, the content of which ranged from 22-42.6%. Moreover, the lowest lipid content was A. flos-aquae, with a value of 3%. Differences in lipids are affected by several factors during the cultivation process, such as temperature, light intensity, incubation time, and nutrient composition in the growth medium [56, 58].

The effect of light intensity on the lipid content of microalgae varies. In some microalgae species, an increase in light intensity results in a higher lipid content. For example, B. braunii and H. pluvialis showed increased lipid levels in cultures of high intensity; H. pluvialis showed a double increase in lipids [58, 59]. Conversely, low-light intensity conditions led to a high lipid content in other species such as Nannochloropsis spp. and A. falcatus [60, 61].

The temperature of the culture also affects the lipid content of the microalgae. For example, increased culture temperature of S. obliquus can increase the lipid content [62]. However, in C. vulgaris, the lipid content increases when the temperature of the culture is reduced [63].

The length of microalgal cultures is also one of the factors that affect differences in lipid content. Mir et al. [64] showed that the lipid content of Cyclotella spp. with a 15-day culture time was the highest—33.06% (w/w). The availability of nutrients in the growth medium is essential for the growth and production of macronutrients. Nitrogen limitations increase lipid accumulation or storage [65]. Similarly, increasing CO2 concentrations can increase the amount of lipids produced by microalgae [66].

Table 3.
Amino acid values of microalgae.
Food Source (amino acid (g/100 g dry matter) Eggs [40] Soy [40] C. vulgaris [40] C. pyrenoidosa [51] Aphanizomenon spp [33]. H. pluvialis [41] S. porticalis [52] S. obliquus [33] N. limnetica [53]
ESSENTIAL AMINO ACIDS
His 2.3 2.6 2 0.82 0.9 0.31 0.9 2.1 2.14
Ile 6.6 5.3 3.8 1.64 2.9 4.32 0.02 3.6 4.63
Leu 8.8 7.7 8.8 3.33 502 3.64 0.81 7.3 9.16
Lys 5.3 6.4 8.4 4.91 3.5 2.68 0.96 5.6 5.27
Met 3.2 1.3 2.2 1.14 0.7 0.65 0.66 1.5 1.69
Phe 5.8 5 5 1.16 2.5 1.4 0.94 4.8 5.1
Thr 5 4 4.8 1.75 3.3 5.47 0.66 5.1 3.72
Try 1.7 1.4 2.1 - 0.7 - - 0.3 -
Val 7.2 5.3 5.5 3.21 3.2 2.45 0.02 6 5.85
NONESSENTIAL AMINO ACIDS
Tyr 4.2 3.7 3.4 1.65 - 2.22 - 3.2 2.97
Ala - 5 7.9 3.63 4.7 5.6 1.31 9 7.72
Arg 6.2 7.4 6.4 3.21 3.8 10.26 0.21 7.1 5.16
Asp 11 1.3 9 2.58 4.7 - 0.33 8.4 7.33
Glu 12.6 19 11.8 6.33 7.8 10.41 0.04 10.7 16.7
Gly 4.2 4.5 5.8 3.19 2.9 6.61 0.75 7.1 8.68
Pro 4.2 5.3 4.8 3.6 2.9 1.24 0.96 3.9 8.17
Ser 6.9 5.8 4.1 4.52 2.9 3.34 0.62 3.8 4.26
Cys 2.3 1.9 1.4 0.54 0.2 0.25 0.23 0.6 1.45


Table 4.
Fatty acid content in several microalgae (mg/g).
Microalgal Species FFA SAFA MUFA PUFA References
C. vulgaris 340 22.0 3.5 73.4 Li et al. [69]
Chlorella kessleri 137.38 46.5 16.0 37.38 Ambrozova et al. [56]
N. limnetica 129.7 48.3 36.2 15.4 Marrez et al. [53]
S. obliquus 100 25.5 16.0 43.3 Salama et al. [70]
B. braunii 120 15.9 13.6 70.5 Lee-Chang et al. [71]
A. falcatus 79.5-86.9 32.1-36.2 27.7-31.1 25.9-27.9 Jayanta et al. [72]
Oscillatoria sp. 83.6 34.74 60.63 4.30 Irmak and Arzu [73],
H. pluvialis 83.41-93.68 27.81-30.36 18.96-20.07 43.15-47.23 Damiani et al. [58]

The fatty acid groups of several freshwater microalgae are shown in Table 4. N. limnetica has the highest saturated fatty acid (SAFA) value (48.3%) [53]. The SAFA group consisted of myristic acid (C14:0) at 3.34%, palmitic acid (C16:0) at 30.6%, and stearic acid (C18:0) at 6.06%. SAFAs are saturated fatty acids that contribute to many health-related functions. For example, cholesterol contributes to increasing low-density lipoprotein (LDL) levels [67]. Furthermore, SAFAs such as butyrate, caprate, lauric, myristic, palmitic, and stearic acid are useful for mammals' growth, development, and survival [68] (Table 4).

The highest monounsaturated fatty acid (MUFA) content was found in Oscillatoria spp., with a value of 60.63% [71]. MUFAs have the function of improving plasma lipid profiles, including those of both LDL and HDL concentrations [74]. The highest polyunsaturated fatty acid (PUFA) content was 73.4%, recorded in C. vulgaris [69]; PUFA consisted of palmitoleic acid (C16:2) (2%), linoleic acid (C18:2) (3.8%), linolenic acid (C18:3) (3.8%), arachidonic acid (C20:4) (2.7%), eicosapentaenoic acid (C20:5) (35.1%) and docosatetraenoic acid (C22:4) (16.5%). PUFAs such as linolenic acid and linoleic acid are essential fatty acids beneficial for the body, one of which is preventing coronary heart disease [75].

Fatty acids are also major components of the phospholipid present in cell membranes [76]. Moreover, fatty acids are an energy storage material and act as signaling molecules that regulate cell growth, differentiation, and gene expression [77, 78].

3.3. Carbohydrates

Microalgae are good sources of carbohydrates. Carbohydrates in microalgae are found in the cytosol, but also in organelles [79]. Carbohydrates in microalgae have several functions, such as acting as backup energy storage and structural components in the cell wall. Furthermore, the carbohydrate content can reach as much as 50% (w/w) of microalgal dry weight under high photoconversion efficiency. Therefore, some microalgae species have a high carbohydrate content (Table 2). However, the algal metabolism and carbohydrate composition vary from species to species. Therefore, choosing an algal type with a high carbohydrate content for human consumption is necessary.

The highest carbohydrate content of freshwater microalgal species is found in H. pluvialis, with a range of 47.20-64.22% [29]. In contrast, the lowest carbohydrate content is found in C. vulgaris, with a range of 12-17% [26]. Differences in carbohydrate content can be affected by nutrients and light intensity [80]. For example, at a low light intensity, some microalgae synthesize proteins utilizing stored carbohydrates and this condition causes an overall decrease in the carbohydrate content [31, 81].

Sugars composing microalgae biomass include xylose, arabinose, glucose, maltose, galactose, and mannose [82]. The biomass of carbohydrates depends on the type of microalgal species, the method of cultivation, and the environmental conditions. Therefore, microalgal species can be manipulated to produce increased amounts of carbohydrates. Furthermore, the carbohydrates in microalgae can potentially be used for food [83].

3.4. Vitamins

Vitamins are micronutrients with essential functions in metabolic processes, are needed in small amounts and must be supplied from food. Vitamins have multiple functions that help regulate metabolism; prevent chronic diseases, and maintain appetite, mental health, and immunity. In general, vitamins act as coenzymes or as carriers of electrons or protons that are active in the process of macronutrient breakdown [40].

Algae are vitamin-rich foods. Some microalgae have high amounts of vitamins, such as provitamin A, vitamin E, vitamin B1, and folic acid. Dunaliella tertiolecta can synthesize vitamin B12, B2, E, and provitamin A [84], whereas Tetraselmis suecica is an excellent source of vitamin B1, B3, B5, B6 and C. Similarly, Chlorella spp. is good source of vitamin B12. C. pyrenoidosa accumulates 415 μg of vitamins per 100 g dry weight [85].

E. gracilis is also a vitamin-rich microalga, producing provitamin A, β-carotene, vitamin A, and vitamin E. Vitamin production in microalgae can be increased by applying a two-step culture. First, increased biomass of E. gracilis is achieved through photoheterotrophic culture. However, an increase in vitamin content is achieved through culture under photoautotrophic conditions. These conditions have been shown to increase the content of β-carotene, vitamin E and vitamin C to 71.0 mg/L, 30.1 mg/L, and 86.5 mg/L, respectively. Furthermore, adequate light applied to this species can increase the content of vitamin E by up to 100% [86].

Microalgae can synthesize all the vitamins that plants can produce. The accumulation of vitamins in microalgae is more significant than that in soybeans and cereals but can vary depending on species, season, algal growth stages, and environmental parameters. For example, Porphyridium cruentum can accumulate high levels of tocopherols; specifically, this microalga contains α- and γ-tocopherol contents equal to 55.2 and 51.3 μg/g dry weight. Tocopherol (vitamin E) is a fat-soluble antioxidant considered an essential nutrient due to its ability to protect membrane lipids from oxidative stress. Chlorella is the richest source of vitamin B12 and can serve as an alternative source of vitamins for vegetarians [87].

4. METABOLITES

4.1. Pigments

Pigment production in microalgae is affected by many factors. The availability of nutrients, pH, temperature, and light has been known to affect pigment production. Light and temperature are the most important limiting factors for enzyme production [88]. Pigments are located in the thylakoid membrane. In eukaryotic microalgae, this membrane is found within the chloroplast. However, in cyanobacteria (prokaryotic microalgae), the membrane is located near and parallel to the cell surface [89]. Some groups of freshwater microalgae known to produce pigments are listed in Table 5.

Pigments are grouped into three classes: chlorophyll (chl), carotenoids, and phycobiliproteins [102]. Although the composition of pigments that function in photosynthesis differs among microalgal species, all photosynthetic organisms have chl a as part of their core photosynthetic reaction center. Chl b, c, or d are also accessory pigments. All chlorophyll molecules exhibit two light absorption bands at 450–475 and 630–675 nm [103].

β-Carotene is present in most microalgae as an accessory pigment and has been extensively explored. β-Carotene production can be affected by abiotic factors such as light, intensity, salinity, temperature, and nutrients. The intensity of light can lead to high production of secondary pigments, one of which is β-carotene [104]. Another way to increase the production of β-carotene is to control the availability of nutrients in culture media. Nitrate and sulfate deficiency can induce higher β-carotene production [32]. Compared with inorganic fertilizers, Guillard media were better at inducing high amounts of total carotenoids in Hyaloraphidium contortum and C. vulgaris [105].

Astaxanthin can be produced by freshwater microalgae, green microalgae, and H. pluvialis. H. pluvialis has two stages in its life cycle [106]. Optimal conditions for the growth of H. pluvialis include a temperature of 20 °C, a light intensity of 250 mol photon m2 s-1, a CO2 concentration of ~2.2 mg L-1, a nitrate concentration of up to 10 mM, and a pH of approximately 7.5-8.0 [107-109]. Moreover, in the red phase, pigment accumulation can be triggered by temperature increases to those higher than 27 °C, a light intensity of 500 mol photon m2 s-1, and nitrate concentrations of ~3 mM [84, 106, 109, 110].

4.2. Sterols

Sterols play an essential role in the human body. Sterols are the main constituents of cell membranes. In addition, many sterols surrogates help improve cholesterol metabolism by competition, primarily lowering the content of low-density lipoproteins (LDL). This property is associated with a decrease in cardiovascular disease in humans. Furthermore, there may be a strong association between the so-called phytosterol consumption and an improved immune system [111].

Sterol composition in microalgae show large differences, mostly as a consequence of their phylogenetic variety. Additionally, the pool of sterols may be affected by the precise growth condition. Major sterols present in Microalgae are either cholesterol or β-sitosterol [110], but minor amounts of other sterols may be also present [112]. Additionally, changes in environmental conditions can also change the profiles of sterols. Sterols can be used as antioxidant, anticarcinogenic, and anti-inflammatory compounds, reducing the effects of neurological diseases such as Parkinson's and Alzheimer's diseases and providing anti-hypercholesterolemia and anti-diabetic effects [113, 114].

Martin-Creuzburg and Merkel [115] showed that freshwater microalgae of Chlorophyceae, Trebouxiophyceae, Eustigmatophyceae, Cryptophyceae, and Bacillariophyceae were capable of producing sterols. In addition, the researchers found that seventeen freshwater microalgae produced sterols. The highest producer of sterols was Monoraphidium minutum (15.3 ± 1.1 μg mg L−1); in contrast, the lowest sterol was found in Gomphonema parvulum (2.1 ± 0.2 μg mg L−1).

Table 5.
Pigments produced by freshwater microalgae.
Species Pigments References
Dunaliella salina β-carotene, astaxanthin, zeaxanthin, lutein, cryptoxanthin Dufosse et al. [90]; Rabbani et al. [91]; Hana et al. [92]; Dufoss et al. [90]
H. pluvialis Astaxanthin, canthaxanthin, lutein Buono et al. [93]; Dufosse et al. [90]
C. vulgaris Canthaxanthin, astaxanthin, β-carotene, echinenone Patias et al. [94]
C. sorokiniana Chlorophyll, carotenoids Miazek et al. [95]; Ogbonna et al. [96]
S. obliquus Astaxanthin, Lutein, β-carotene, echinenone Sallehudin et al. [97]; Patias et al. [94]; Qin et al. [98]
Scenedesmus dimorphus Astaxanthin, chlorophyll, lutein, zeaxanthin, Sallehudin et al. [97]; Ahmad et al. [99]
Ankistrodesmus Lutein, chlorophyll, ß-carotene Sallehudin et al. [97]; Ogbonna et al. [96]
B. braunii Neoxanthin, loroxanthin, violaxanthin, lutein, α-carotene, and β-carotene, echinenone Tonegawa et al. [100]; Ambati et al. [101]

The sterol composition of freshwater green algae (Chlorophyta) is very diverse. In addition, many microalgae have been shown to contain unusual and rare sterols of the C30 sterol group, such as 24-propylidenecholesterols (IVs,t) [116]. Several microalgal sterols have not been found in terrestrial higher plants. However, substantial differences in sterol chemical structure, especially in side chain configurations, have been reported even within a single species. For example, the C-24 alkyl group of the sterol moiety in green algae is attached in the 2,4-β orientation [117]. The two main sterols of C. reinhardtii are ergosterol and 7-dehydroporiferasterol but also small amounts of fungisterol, 22-dihydroergosterol, and 22-dihydrochondrillasterol have been found in this algae [118].

5. FUNCTIONAL PROPERTIES

The great potential of microalgal applications encompasses human nutrition, feedstuffs, bio fertilizer, and waste treatment. In addition, it extends to the field of health care in terms of new anti-inflammatory, antiallergic, and analgesic drugs [119]. For example, C. vulgaris and Spirulina produce sulfated polysaccharides, which are considered nutraceuticals recommended in cancer prevention a/o treatment [120, 121].

5.1. Antioxidants

Antioxidants can help optimize human physiology and prevent diseases [122, 123]. The ability of microalgae to act as antioxidants is sometimes more remarkable than that of plants or fruits. Vitamins, carotenoids, and polyphenols such as flavonoids are responsible for the antioxidant activity of microalgae [124]. High amounts of phycobiliprotein in microalgae lead to an increase in antioxidants in several Cyanobacteria [125]. The antioxidant activity of the extracted-freshwater microalgae is rarely reported.

In a study conducted by Shanab et al. [125], freshwater microalgal extracts (Anabaena oryzae, Nostoc humifusum, Nostoc muscorum, Oscillatoria sp., Spirulina platensis, Phormedium fragile, Wollea saccata, and C. vulgaris) were tested for antioxidant activity. The result showed that Spirulina has high antioxidant activity compared to other species, with values of 69.3% and 75.9%, respectively. Cyanobacteria has also been reported as potential antioxidants. The ethanolic extract of Euglena cantabrica has a radical scavenging inhibition of 71-100%, which is even higher than that of butylated hydroxytoluene (BHT) used as control (26%). It is postulated that catechin and chlorogenic acid are the phenolic compounds responsible for the antioxidant activity [126]. Nevertheless, there are other antioxidants compounds such as flavonoids and carotenoids. The extract from Scenedesmus sp, C. vulgaris, C. reinhardtii, contain polyphenols, flavonoid, and carotenoids [127].

Moreover, sterols such as Desmosterol, Sitosterol, Ergosterol, Occelasterol, Cholesterol, and Clionasterol can act as antioxidants [128]. Seventeen freshwater microalgae were analyzed for the sterol producer. Monoraphidium minutum and Ankistrodesmus fusiformis are the highest producers of total sterol [115]. Unfortunately, the investigation of sterol from freshwater microalgae is still rare. Hence, further exploration of freshwater microalgae-sterol as an antioxidant is very open.

5.2. Anti-inflammatory

Inflammation is an initial immune reaction when foreign pathogens disrupt cellular homeostasis. Various inflammatory mediators, including cytokines, chemokines, cyclooxygenase-2 (COX-2), prostaglandins (PGs), and nitric oxide synthase (NOS), can cause various diseases [129, 130]. Compounds from the ethanolic extract of freshwater microalgae, Micractinium spp., can decrease the expression of TNF-α and IL-6 [131]. Furthermore, Chloromonas reticulata compounds extracted using ethanol can reduce the expression of major regulatory inflammatory factors, such as NOS and COX-2. In addition, containing active substances, these extracts can reduce mRNA levels associated with inflammation [132].

Lipid components influence the anti-inflammatory effects shown by some species of freshwater microalgae. For example, lipid extracts can inhibit the activity of COX enzymes, which are inflammatory mediators that induce the conversion of arachidonic acid into prostaglandins and decrease cytokine (TNF-α, IL-1β, and IL-6) production [133]. In addition, phytosterols extracted from Nannochloropsis oculata exert anti-inflammatory effects by lowering NOS and COX-2 [134]. Furthermore, fucoxanthin, PUFA, EPA, and DHA, such as the compound of microalgae fatty acids oxylipins, act as an anti-inflammatory [135]. Moreover, diet PUFAs from microalgae reduce inflammatory bowel disease symptoms [136].

5.3. Antibacterial

Freshwater microalgae such as E. viridis, Microcystis aeruginosa, C. vulgaris and S. platensis have demonstrated antibacterial activity in trials involving pathogenic bacteria such as Escherichia coli, Staphylococcus aureus and Salmonella typhi [137]. Additionally, Planktochlorella nurekis at a concentration of 0.75–6 mg/mL inhibits a group of pathogenic bacteria including Salmonella enterica var. Enteritidis, S. enterica var. Infantis, Campylobacter jejuni, E. coli [138]. Furthermore, PUFA-extracted from P. nurekis at a concentration of 100 µg.mL-1 inhibits growth of S. aureus and a mixed culture of Enterococcus faecalis and Pseudomonas aeruginosa [139]. Fatty acids, SAFAs, MUFAs, and PUFAs, can act as antibacterial compounds [135], as shown with algae containing lauric acid (C12:0), myristic acid (C14:0), pentadecanoic acid (C15: 0), and stearic acid (C18:0) which decrease the metabolic activity of Gram-negative bacteria such as P. aeruginosa and E. coli PCM 2209 [140].

There are various ways to apply microalgae to combat pathogenic bacteria, using extracts, homogenates, pure compounds or whole cells [140, 141] thus promoting the antibacterial activity exerted by specific compounds such as fatty acids, glycolipids, phenolics, terpenes, diketones, or alkaloid indoles [142]. For example, an organic extract of Spirogyra sp. showed inhibition on S. aureus, E coli, St. xylosus and P. aeruginosa at a concentration of 0.1 g.mL-1 [143].

H. pluvialis, Scenedesmus sp., Chlorella sp, and Spirulina sp. were challenged against Gram-positive and Gram-negative bacteria. Vigorous antibacterial activity was found on the 70% methanolic extract of Scenedesmus sp. NT8c and Chlorella sp. with a minimum inhibitory concentration (MIC) value of 1 mg.mL-1. Among all tested microorganisms, E. coli, S. typhoid, and P. syringae failed to be inhibited by the extract [144].

5.4. Antiviral

Several freshwater microalgae have demonstrated antiviral activity. For example, extracts of Anabaena sphaerica, Chroococcus turgidus, Oscillatoria limnetica, Cosmarium sp., and S. platensis inhibit adenovirus type 40. Methanol extract of S. platensis showed high antiviral activity with IC50 viral titer values of 2 mg.mL-1 [145]. The best antiviral components were found in S. platensis extracts. S. platensis extracts also have good antiviral capacity against human immunodeficiency virus type 1. This ability is possibly due to the sulfoquinovosyl diacylglycerol (SQDG) compound found in Spirulina [146]. SQDG isolated from S. platensis was reported to have antiviral activity against herpes simplex virus type 1 (HSV-1) with an IC50 value of 6.8 g.ml-1 [147].

Pigments, pheophorbide a, carotenoids, astaxanthin and phycobiliproteins (allophycocyanin, phycocyanin) have antiviral activity. Pheophorbide a (PPba) has antiproliferative activity because it exhibits several antiviral effects, particularly against enveloped viruses [118]. This pigment can bind to viral cell receptors and impact after entering the virus. Carotenoids can reduce the harmful effects of some viruses, such as those associated with cytokine storms [148]. Pressurized liquid extraction (PLE) of carotenoids from the ethanol extract of H. pluvialis has been reported to inhibit HSV-1 growth by 85% [149]. Polysaccharides in microalgae have antiviral potential by preventing viruses from reaching their host cells. In addition, various freshwater microalgae produce glycoproteins with antiviral potential. For instance, microalgae lectins can attach to carbohydrates involved in HIV glycosylation to bind to CD4 cellular receptor target cells [150]. The water soluble S. platensis polysaccharide showed HSV-1 inhibitory activity at IC50 value of 21.32 µg.mL-1 [151].

5.5. Anticancer

The bioactive compounds of microalgae can be used as anticancer agents. Protein hydrolysates of C. vulgaris show anticancer activity [152]. The peptide fraction isolated from C. vulgaris inhibits the growth of the hyperdiploid human cell, (AGS cell line) with a range of IC50 values of 70.7 ± 1.2 µg.mL-1 to 1.74 ± 0.3 g ml-1 [153]. Granulocystopsis sp. extracts show high cytotoxicity against prostate, breast, colorectal, melanoma and lung cancer cells (<20 mg.ml-1) but the positive control using doxorubicin showed higher anticancer activity than the microalgae extract on Vero (normal) cells [154]. However, microalgae extract has an apoptotic mechanism in the tumor pathway positively associated with doxorubicin's anticancer effect [155]. Furthermore, prostate cancer showed a sensitivity effect during the administration of the methanol extract of Granulocystopsis spp. The values of IC50 of the Granulocystopsis spp methanolic extract were lower than 20 μg.mL-1 [154]. The US National Center Institute (NCI) determines the level of cytotoxicity: IC50 > 100 mg/ml = inactive, IC50 20-100 mg/ml = moderately active and IC50 < 20 mg/ml = active [156].

Anticancer bioactive compounds include polysaccharides, glycoproteins, astaxanthin, lycopene, ß-carotene, EPA, DHA, polyphenols and flavonoids [157]. Carotenoids, astaxanthin, ß-carotene, lutein, lycopene, and canthaxanthin inhibit the proliferation of human lung cancer cells (NCI-H226) and suppress the growth factors of breast and endometrial cancer cells [158]. Several freshwater microalgae inhibit cancer cells such as breast, colon, prostate, pancreatic, and endometrial cancers, namely Nannochloropsis gaditana, Isochrysis galbana, A. flos-aquae and S. platensis [6, 7]. Aqueous extract from Geitlerinema carotinosum, Nostoc linckia can inhibit rat glioma cell (C6 cell lines) with IC50 levels of 112.69 and 121.48 μg.mL-1 [159]. Phytochemical from C. vulgaris inhibit MCF7 breast cancer cell with IC50 value of 100 μg.mL-1 [8]. Moreover, Coibamide-A from Leptolyngbya sp has a small value of IC50 (300 ng.mL-1) toward human lung cancer NCIH 460 [160].

CONCLUSION AND DEVELOPMENTAL PROSPECTS

The demand for food supply in the future will be greater than it is now, so it is necessary to increase food production by more than 60% to meet the global population's needs. Based on reviews on nutritional and functional properties, freshwater microalgae have the potential to continue to develop as food alternatives.

Countries in tropical regions rich in sunlight have better opportunities to explore and utilize microalgae. Therefore, countries that do not have beaches or adjacent seas can switch to the cultivation of freshwater microalgae, which have been proven to have excellent nutritional contents. Microalgae production must be modified to the desired characteristics and factors that affect each species to obtain optimal results. Each species has different prerequisites for the growth and production of metabolites.

Apart from Chlorella sp., information regarding the safety issues and the large scale production of freshwater microalgae is still limited. This limitation due to inadequate data regarding the toxic compounds, nutrition value, growth parameters, and economic feasibility of freshwater microalgae. Therefore, in the future, the exploration of freshwater microalgae as foods, should be focused on those topics.

Researchers can also develop various processed foods from freshwater microalgae. Proper product development, especially in terms of production and processing, will help each country achieve its goal of addressing food security successfully.

The prospect of good development of the use of freshwater microalgae needs to be considered because, in general, the development of food alternatives requires adjustments of consumers. Therefore, freshwater microalgal food alternatives need to receive a good reception from the public and are expected to compete in the market. The challenge to overcome is to convert freshwater microalgal biomass into nutritious foods, good taste, and good functional properties. This is because the public tends to judge foods based on the nutritional content and functional properties and the taste and appearance of a product. We hope that freshwater microalgae will soon be implemented to help solve the global food crisis.

LIST OF ABBREVIATIONS

ABTS = 2,2'-azino-bis (3-ethylbenzothiazoline6-sulphonic acid)
CD4 = cluster of differentiation 4
DHA = Docosahexaenoic Acid
DPPH = 2,2-diphenyl-1-picrylhydrazyl
EPA = Eicosapentaenoic Acid
FAO = Food and Agriculture Organization
HIV = Human Immunodeficiency Virus
IC50 = Inhibitory Concentration where 50% of cell is inhibited
IL = Inter Leukin
mRNA = messenger Ribonucleic Acid
MIC = Minimum Inhibitory Concentration
MUFAs = Mono Unsaturated Fatty Acids
PUFAs = Poly Unsaturated Fatty Acids
SAFAs = Saturated fatty Acids
TNF = Tumour Necrosis Factor
UNU = United Nation University
WHO = World Health Organization

AUTHOR CONTRIBUTIONS

A.A.P., M.W., and Y.D.J. conducted a literature review and contributed to discussions, A.M., and R.N provided a Table data. M.W. provided guidance, led discussions, and approval of the complete version. A.A.P. Y.D.J., A.M. revised the paper.

CONSENT FOR PUBLICATION

Not applicable.

FUNDING

The study was supported by the Ministry of Education, Culture, Research and Technology for the international cooperation grant granted (No. 539.4.4/UN10. C10/PN/2021).

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

The author Ministry of Education, Culture, Research and Technology for the international cooperation grant granted (No. 539.4.4/UN10. C10/PN/2021).

REFERENCES

1
Ben Abdallah M, Fekete-Farkas M, Lakner Z. Exploring the link between food security and food price dynamics: A bibliometric analysis. Agriculture 2021; 11(3): 263.
2
Global Network Against Food Crises. Global Report on Food Crisis 2021; 1-304.
3
Myers SS, Smith MR, Guth S, et al. Climate change and global food systems: Potential impacts on food security and undernutrition. Annu Rev Public Health 2017; 38(1): 259-77.
4
Wheeler T, von Braun J. Climate change impacts on global food security. Science 2013; 341(6145): 508-13.
5
Mourelle M, Gómez C, Legido J. Review the potential use of marine microalgae and cyanobacteria in cosmetics and thalassotherapy. Cosmetics 2017; 4(4): 46.
6
Potvin G, Zhang Z. Strategies for high-level recombinant protein expression in transgenic microalgae: A review. Biotechnol Adv 2010; 28(6): 910-8.
7
Khan MI, Shin JH, Kim JD. The promising future of microalgae: current status, challenges, and optimization of a sustainable and renewable industry for biofuels, feed, and other products. Microb Cell Fact 2018; 17(1): 36.
8
Moejes FW, Moejes KB. Algae for Africa: Microalgae as a source of food, feed and fuel in Kenya. Afr J Biotechnol 2017; 16(7): 288-301.
9
Araújo R, Vázquez Calderón F, Sánchez López J, et al. Current status of the algae production industry in europe: An emerging sector of the blue bioeconomy. Front Mar Sci 2021; 7626389
10
Rajkumar P, Yaakob Z, Takriff MS. Potential of the micro and macro for biofuel production: A brief review. BioResources 2014; 9: 1606-33.
11
Madeira MS, Cardoso C, Lopes PA, et al. Microalgae as feed ingredients for livestock production and meat quality: A review. Livest Sci 2017; 205: 111-21.
12
Mondal M, Goswamil S, Ghosh A, et al. Production of biodiesel from microalgae through biological carbon capture: A review. 3 Biotech 2017; 7: 1-21.
13
Mutanda T, Naidoo D, Bwapwa JK, Anandraj A. Biotechnological applications of microalgal oleaginous compounds: Current trends on microalgal bioprocessing of products. Front Energy Res 2020; 8598803
14
Madadi R, Maljaee H, Serafim LS, Ventura SPM. Microalgae as contributors to produce biopolymers. Mar Drugs 2021; 19(8): 466.
15
Hossain N, Mahlia TMI, Saidur R. Latest development in microalgae-biofuel production with nano-additives. Biotechnol Biofuels 2019; 12(1): 125.
16
Mohsenpour SF, Hennige S, Willoughby N, Adeloye A, Gutierrez T. Integrating micro-algae into wastewater treatment: A review. Sci Total Environ 2021; 752142168
17
Vieira MV, Pastrana LM, Fuciños P. Microalgae encapsulation systems for food, pharmaceutical and cosmetics applications. Mar Drugs 2020; 18(12): 644.
18
Caporgno MP, Mathys A. Trends in microalgae incorporation into innovative food products with potential health benefits. Front Nutr 2018; 5: 58.
19
Sathasivam R, Radhakrishnan R, Hashem A, Abd Allah EF. Microalgae metabolites: A rich source for food and medicine. Saudi J Biol Sci 2019; 26(4): 709-22.
20
Barkia I, Saari N, Manning SR. Microalgae for High-Value Products Towards Human Health and Nutrition. Mar Drugs 2019; 17(5): 304.
21
Matos J, Cardoso C, Bandarra NM, Afonso C. Microalgae as healthy ingredients for functional food: a review. Food Funct 2017; 8(8): 2672-85.
22
Andrade LM, Andrade CJ, Dias MC, Nascimento AO, Mendes MA. Chlorella and Spirulina microalgae as sources of functional foods, nutraceuticals, and food supplements; an overview. MOJ Food Processing & Technology 2018; 6(1): 45-58.
23
Bito T, Okumura E, Fujishima M, Watanabe F. Potential of Chlorella as a dietary supplement to promote human health. Nutrients 2020; 12(9): 2524.
24
Ru ITK, Sung YY, Jusoh M, Wahid MEA, Nagappan T. Chlorella vulgaris: a perspective on its potential for combining high biomass with high value bioproducts. Appl Psychol 2020; 1: 1-10.
25
Torres-Tiji Y, Fields FJ, Mayfield SP. Microalgae as a future food source. Biotechnol Adv 2020; 41107536
26
Wolkers H, Barbosa MJ, Kleinegris DM, Bosma R, Wijffels RH, Harmsen P. Microalgae: the green gold of the future? large-scale sustainable cultivation of microalgae for the production of bulk commodities 2011.https://edepot.wur.nl/170781
27
Ramaraj R, Yuwalee U, Natthawud D. Cultivation of green microalga, chlorella vulgaris for biogas purification. International Journal of New Technology and Research 2016; 2: 117-22. [IJNTR].
28
Yadavalli R, Rao CS, Rao RS, Potumarthi R. Dairy effluent treatment and lipids production by Chlorella pyrenoidosa and Euglena gracilis : study on open and closed systems. Asia-Pac J Chem Eng 2014; 9(3): 368-73.
29
Gacheva G, Dimitrova P, Pilarski P. New strain Haematococcus Cf. pluvialis Rozhen-12 – growth, biochemical characteristics and future perspectives. Genet Plant Physiol 2015; 5: 29-38.
30
Arguelles EDLR. Proximate analysis, antibacterial activity, total phenolic content and antioxidant capacity of a green microalgae Scenedesmus quadricauda (Turpin) Brébisson. Asian J Microbiol Biotechnol Environ Sci 2018; 20: 150-8.
31
Khatoon H, Rahman NA, Suleiman SS, Banerjee S, Abol-Munafi AB. Growth and proximate composition of Scenedesmus obliquus and Selenastrum bibraianum cultured in different media and condition. Proc Natl Acad Sci, India, Sect B Biol Sci 2019; 89(1): 251-7.
32
Becker EW. Microalgae for aquaculture: the nutritional value of microalgae for aquaculture.Handbook of Microalgal Culture 2004; 380-91.
33
Becker EW. Micro-algae as a sourch of protein. biotechnology advances 2007; 25: 207-10.
34
Patel VK, Sundaram S, Patel AK, Kalra A. · Shanthy S, Akash KP, Alok K. Characterization of seven species of Cyanobacteria for high-quality biomass production. Arab J Sci Eng 2018; 43(1): 109-21.
35
Nakanishi A, Yuri S, Nanami O. Improvement of growth of Chlamydomonas reinhardtii in CO2 – stepwisely aerating condition. J Appl Biotechnol Rep 2021; 8: 37-40.
36
Dineshbabu G, Goswami G, Kumar R, Sinha A, Das D. Microalgae–nutritious, sustainable aqua- and animal feed source. J Funct Foods 2019; 62103545
37
Bleakley S, Hayes M. Algal proteins: Extraction, application, and challenges concerning production. Foods 2017; 6(5): 33.
38
Chronakis IS, Madsen M. Algal Proteins 2011.
39
Sousa I, Luísa G, Batista AP, Raymundo A, Bandarra NM. Microalgae in novel food products.Food Chemistry Research Developments 2008; 1-37.
40
Koyande AK, Chew KW, Rambabu K, Tao Y, Chu DT, Show PL. Microalgae: A potential alternative to health supplementation for humans. Food Sci Hum Wellness 2019; 8(1): 16-24.
41
Zhu Y, Zhao X, Zhang X, Liu H, Ao Q. Amino acid, structure and antioxidant properties of Haematococcus pluvialis protein hydrolysates produced by different proteases. Int J Food Sci dan. Tech (Singap) 2021; 56: 185-95.
42
Metsoviti MN, Papapolymerou G, Karapanagiotidis IT, Katsoulas N. Comparison of growth rate and nutrient content of five microalgae species cultivated in greenhouses. Plants 2019; 8(8): 279.
43
Béchet Q, Shilton A, Fringer OB, Muñoz R, Guieysse B. Mechanistic modeling of broth temperature in outdoor photobioreactors. Environ Sci Technol 2010; 44(6): 2197-203.
44
Béchet Q, Shilton A, Park JBK, Craggs RJ, Guieysse B. Universal temperature model for shallow algal ponds provides improved accuracy. Environ Sci Technol 2011; 45(8): 3702-9.
45
Serra-Maia R, Bernard O, Gonçalves A, Bensalem S, Lopes F. Influence of temperature on Chlorella vulgaris growth and mortality rates in a photobioreactor. Algal Res 2016; 18: 352-9.
46
Renaud SM, Thinh LV, Lambrinidis G, Parry DL. Effect of temperature on growth, chemical composition and fatty acid composition of tropical Australian microalgae grown in batch cultures. Aquaculture 2002; 211(1-4): 195-214.
47
Baiee MA, Salman JM. Effect of phosphorus concentration and light intensity on protein content of microalga Chlorella vulgaris. Mesop Environ A 2016; 2: 75-86.
48
He Q, Yang H, Wu L, Hu C. Effect of light intensity on physiological changes, carbon allocation and neutral lipid accumulation in oleaginous microalgae. Bioresour Technol 2015; 191: 219-28.
49
Menegol T, Diprat AB, Rodrigues E, Rech R. Effect of temperature and nitrogen concentration on biomass composition of Heterochlorella luteoviridis. Food Sci Technol (Campinas) 2017; 37(spe): 28-37.
50
Christaki E, Florou-Paneri P, Bonos E. Microalgae: A novel ingredient in nutrition. Int J Food Sci Nutr 2011; 62(8): 794-9.
51
Cheng P, Chu R, Zhang X, et al. Screening of the dominant Chlorella pyrenoidosa for biofilm attached culture and feed production while treating swine wastewater. Bioresour Technol 2020; 318124054
52
Kumar J, Khan S, Mandotra SK, et al. Nutraceutical profile and evidence of alleviation of oxidative stress by Spirogyra porticalis (Muell.) Cleve inhabiting the high altitude Trans-Himalayan Region. Sci Rep 2019; 9(1): 4091.
53
Marrez D, Cieślak A, Gawad R, et al. Effect of freshwater microalgae Nannochloropsis limnetica on the rumen fermentation in vitro. J Anim Feed Sci 2017; 26(4): 359-64.
54
Kay RA, Barton LL. Microalgae as food and supplement. Crit Rev Food Sci Nutr 1991; 30(6): 555-73.
55
Sheehan J, Dunahay T, Benemann J, Roessler P. A look back at the u.s. department of energy's aquatic species program-biodiesel from algae, Prepared for US Department of Energy's Office of Fuels Development, by National Renewable Energy Laboratory 1998.
56
Ambrozova J, Misurcova L, Vicha R, et al. Influence of extractive solvents on lipid and fatty acids content of edible freshwater algal and seaweed products, the green Microalga Chlorella kessleri and the Cyanobacterium Spirulina platensis. Molecules 2014; 19(2): 2344-60.
57
Allard B, Templier J. Comparison of neutral lipid profile of various trilaminar outer cell wall (TLS)-containing microalgae with emphasis on algaenan occurrence. Phytochemistry 2000; 54(4): 369-80.
58
Damiani MC, Popovich CA, Constenla D, Leonardi PI. Lipid analysis in Haematococcus pluvialis to assess its potential use as a biodiesel feedstock. Bioresour Technol 2010; 101(11): 3801-7.
59
Ruangsomboon S. Effect of light, nutrient, cultivation time and salinity on lipid production of newly isolated strain of the green microalga, Botryococcus braunii KMITL 2. Bioresour Technol 2012; 109: 261-5.
60
Sukenik A, Carmeli Y, Berner T. Regulation of fatty acid composition by irradiance level in the eustigmatophyte Nannochloropsis sp. J Phycol 1989; 25(4): 686-92.
61
George B, Pancha I, Desai C, et al. Effects of different media composition, light intensity and photoperiod on morphology and physiology of freshwater microalgae Ankistrodesmus falcatus – A potential strain for bio-fuel production. Bioresour Technol 2014; 171: 367-74.
62
Vitova M, Bisova K, Kawano S, Zachleder V. Accumulation of energy reserves in algae: From cell cycles to biotechnological applications. Biotechnol Adv 2015; 33(6): 1204-18.
63
Converti A, Casazza AA, Ortiz EY, Perego P, Del Borghi M. Effect of temperature and nitrogen concentration on the growth and lipid content of Nannochloropsis oculata and Chlorella vulgaris for biodiesel production. Chem Eng Process 2009; 48(6): 1146-51.
64
Mir Y, Brakez Z, Alem YE, Bazzi L. Investigation of lipid production and fatty acid composition in some native microalgae from Agadir region in Morocco. Afr J Biotechnol 2020; 19: 755-62.
65
Cointet E, Wielgosz-Collin G, Bougaran G, Rabesaotra V, Gonçalves O, Méléder V. Effects of light and nitrogen availability on photosynthetic efficiency and fatty acid content of three original benthic diatom strains. PLoS One 2019; 14(11): e0224701.
66
Widjaja A, Chien C-C, Ju Y-H. Study of increasing lipid production from fresh water microalgae Chlorella vulgaris. J Taiwan Inst Chem Eng 2009; 40(1): 13-20.
67
Te Morenga L, Montez JM. Health effects of saturated and trans-fatty acid intake in children and adolescents: Systematic review and meta-analysis. PLoS One 2017; 12(11)e0186672
68
German JB, Dillard CJ. Saturated fats: What dietary intake? Am J Clin Nutr 2004; 80(3): 550-9.
69
Li C, Yang H, Xia X, et al. High efficient treatment of citric acid effluent by Chlorella vulgaris and potential biomass utilization. Bioresour Technol 2013; 127: 248-55.
70
Salama ES, Kim HC, Abou-Shanab RAI, et al. Biomass, lipid content, and fatty acid composition of freshwater Chlamydomonas mexicana and Scenedesmus obliquus grown under salt stress. Bioprocess Biosyst Eng 2013; 36(6): 827-33.
71
Lee-Chang KJ, Albinsson E, Clementson L, Revill AT, Jameson I, Blackburn SI. Australian strains of Botryococcus braunii examined for potential hydrocarbon and carotenoid pigment production and the effect of brackish water. Energies 2020; 13(24): 6644.
72
Jayanta T, Chandra KM, Chandra GB. Growth, Total Lipid content and Fatty Acid Profile of a Native Strain of the Freshwater Oleaginous Microalgae Ankistrodesmus falcatus (Ralf) grown under Salt Stress Condition. Int Res J Biol Sci 2012; 1(8): 27-35.
73
Irmak SO, Arzu AB. Determination of the fatty-acid composition of four native microalgae species. SC Adv Res Rev 2020; 4: 001-8.
74
Lopes LL, do Carmo M, Peluzio G, Hermsdorf HHM. Monounsaturated fatty acid intake and lipid metabolism. J Vasc Bras 2016; 15: 52-60.
75
Lunn J, Theobald HE. The health effects of dietary unsaturated fatty acids. Nutr Bull 2006; 31(3): 178-224.
76
Burdge GC. Is essential fatty acid interconversion an important source of PUFA in humans? Br J Nutr 2019; 121(6): 615-24.
77
Das UN. Biological significance of essential fatty acids. J Assoc Physicians India 2006; 54: 309-19.
78
Calder PC. Functional roles of fatty acids and their effects on human health. JPEN J Parenter Enteral Nutr 2015; 39(1_suppl)(Suppl.): 18S-32S.
79
Oliveira O, Gianesella S, Silva V, Mata T, Caetano N. Lipid and carbohydrate profile of a microalga isolated from wastewater. Energy Procedia 2017; 136: 468-73.
80
Ho SH, Chen CY, Chang JS. Effect of light intensity and nitrogen starvation on CO2 fixation and lipid/carbohydrate production of an indigenous microalga Scenedesmus obliquus CNW-N. Bioresour Technol 2012; 113: 244-52.
81
Allakhverdiev SI, Nishiyama Y, Takahashi S, Miyairi S, Suzuki I, Murata N. Systematic analysis of the relation of electron transport and ATP synthesis to the photodamage and repair of photosystem II in Synechocystis. Plant Physiol 2005; 137(1): 263-73.
82
Harun R, Danquah MK, Forde GM. Microalgal biomass as a fermentation feedstock for bioethanol production. J Chem Technol Biotechnol 2009; 85: n/a.
83
Markou G, Angelidaki I, Georgakakis D. Microalgal carbohydrates: An overview of the factors influencing carbohydrates production, and of main bioconversion technologies for production of biofuels. Appl Microbiol Biotechnol 2012; 96(3): 631-45.
84
Fabregas J, Herrero C. Vitamin content of four marine microalgae. Potential use as source of vitamins in nutrition. J Ind Microbiol 1990; 5(4): 259-63.
85
Bito T, Bito M, Asai Y, et al. Characterization and quantitation of Vitamin B12 compounds in various Chlorella supplements. J Agric Food Chem 2016; 64(45): 8516-24.
86
Kusmic C, Barsacchi R, Barsanti L, Gualtieri P, Passarelli V. Euglena gracilis as source of the antioxidant vitamin E. Effects of culture conditions in the wild strain and in the natural mutant WZSL. J Appl Phycol 1998; 10(6): 555-9.
87
Mobin SMA, Chowdhury H, Alam F. Commercially important bioproducts from microalgae and their current applications – A review. Energy Procedia 2019; 160: 752-60.
88
Begum H, Yusoff FMD, Banerjee S, Khatoon H, Shariff M. Availability and Utilization of Pigments from Microalgae. Crit Rev Food Sci Nutr 2016; 56(13): 2209-22.
89
Geada P, Vasconcelos V, Vicente A, Fernandes B. Microalgal biomass cultivation.Algal Green Chemistry 2017; 257-84.
90
Dufossé L, Galaup P, Yaron A, et al. Microorganisms and microalgae as sources of pigments for food use: A scientific oddity or an industrial reality? Trends Food Sci Technol 2005; 16(9): 389-406.
91
Rabbani S, Beyer P, Lintig J, Hugueney P, Kleinig H. Induced β-carotene synthesis driven by triacylglycerol deposition in the unicellular alga dunaliella bardawil. Plant Physiol 1998; 116(4): 1239-48.
92
Abd El-Baky HH, El-Baroty GS. The potential use of microalgal carotenoids as dietary supplements and natural preservative ingredients. J Aquat Food Prod Technol 2013; 22(4): 392-406.
93
Buono S, Langellotti AL, Martello A, Rinna F, Fogliano V. Functional ingredients from microalgae. Food Funct 2014; 5(8): 1669-85.
94
Patias LD, Fernandes AS, Petry FC, Mercadante AZ, Jacob-Lopes E, Zepka LQ. Carotenoid profile of three microalgae/cyanobacteria species with peroxyl radical scavenger capacity. Food Res Int 2017; 100(Pt 1): 260-6.
95
Miazek K, Remacle C, Richel A, Goffin D. Beech wood Fagus sylvatica dilute-acid hydrolysate as a feedstock to support Chlorella sorokiniana biomass, fatty acid and pigment production. Bioresour Technol 2017; 230: 122-31.
96
Ogbonna JC, Nweze NO, Ogbonna CN. Effects of light on cell growth, chlorophyll, and carotenoid contents of Chlorella sorokiniana and Ankistrodesmus falcatus in poultry dropping medium. J Appl Biol Biotechnol 2021; 92: 157-63.
97
Sallehudin NJ, Raus RA, Mustapa M, Othman R, Mel M. Screening of lutein content in several freshwater microalgae. Int Food Res J 2018; 25: 2307-12.
98
Qin S, Liu GX, Hu ZY. The accumulation and metabolism of astaxanthin in Scenedesmus obliquus (Chlorophyceae). Process Biochem 2008; 43(8): 795-802.
99
Ahmad N, Mounsef JR, Lteif R. Pigment production by SCENEDESMUS DIMORPHUS using different low‐cost and alternative culture media. J Chem Technol Biotechnol 2022; 97(1): 287-94.
100
Tonegawa I, Okada S, Murakami M, Yamaguchi K. Pigment composition of the green microalga Botryococcus braunii Kawagushi-1. Fish Sci 1998; 64(2): 305-8.
101
Ambati RR, Gogisetty D, Aswathanarayana RG, et al. Industrial potential of carotenoid pigments from microalgae: Current trends and future prospects. Crit Rev Food Sci Nutr 2019; 59(12): 1880-902.
102
Masojdek J, Koblek M, Torzillo G. Photosynthesis in microalgae.Handbook of Microalgal Culture 2007; 20-39.
103
Pagels F, Salvaterra D, Amaro HM, Guedes AC. Pigments from microalgae 2020.
104
Raja R, Hemaiswarya S, Rengasamy R. Exploitation of Dunaliella for β-carotene production. Appl Microbiol Biotechnol 2007; 74(3): 517-23.
105
Brito J, Caña E, Guevara M, Subero J, Colivet J. Effect of three sources of nutrients on biomass and pigment production of freshwater microalgae Hyaloraphidium contortum. Revista Bio Ciencias 2016; 4: 15-26.
106
Panis G, Carreon JR. Commercial astaxanthin production derived by green alga Haematococcus pluvialis : A microalgae process model and a techno-economic assessment all through production line. Algal Res 2016; 18: 175-90.
107
García-Malea MC, Brindley C, Río ED, Acién FG, Fernández JM, Molina E. Modelling of growth and accumulation of carotenoids in Haematococcus pluvialis as a function of irradiance and nutrients supply. Biochem Eng J 2005; 26(2-3): 107-14.
108
Jonker JGG, Faaij APC. Techno-economic assessment of micro-algae as feedstock for renewable bio-energy production. Appl Energy 2013; 102: 461-75.
109
Giannelli L, Yamada H, Katsuda T, Yamaji H. Effects of temperature on the astaxanthin productivity and light harvesting characteristics of the green alga Haematococcus pluvialis. J Biosci Bioeng 2015; 119(3): 345-50.
110
Evens TJ, Niedz RP, Kirkpatrick GJ. Temperature and irradiance impacts on the growth, pigmentation and photosystem II quantum yields of Haematococcus pluvialis (Chlorophyceae). J Appl Phycol 2008; 20(4): 411-22.
111
Plat J, Baumgartner S, Vanmierlo T, et al. Plant-based sterols and stanols in health & disease: “Consequences of human development in a plant-based environment?”. Prog Lipid Res 2019; 74: 87-102.
112
Fagundes MB, Falk RB, Facchi MMX, et al. Insights in cyanobacteria lipidomics: A sterols characterization from Phormidium autumnale biomass in heterotrophic cultivation. Food Res Int 2019; 119: 777-84.
113
Fagundes MB, Alvarez-Rivera G, Vendruscolo RG, et al. Green microsaponification-based method for gas chromatography determination of sterol and squalene in cyanobacterial biomass. Talanta 2021; 224121793
114
Volkman JK. Sterols in microalgae.The Physiology of Microalgae; Developments in Applied Phycology 2016; 485-505.
115
Martin-Creuzburg D, Merkel P. Sterols of freshwater microalgae: potential implications for zooplankton nutrition. J Plankton Res 2016; 38(4): 865-77.
116
Stonik V, Stonik I. Sterol and Sphingoid Glycoconjugates from Microalgae. Mar Drugs 2018; 16(12): 514-34.
117
Volkman J. Sterols in microorganisms. Appl Microbiol Biotechnol 2003; 60(5): 495-506.
118
Miller MB, Haubrich BA, Wang Q, Snell WJ, Nes WD. Evolutionarily conserved Δ25(27)-olefin ergosterol biosynthesis pathway in the alga Chlamydomonas reinhardtii. J Lipid Res 2012; 53(8): 1636-45.
119
Raposo M, De Morais R, Bernardo de Morais A. Bioactivity and applications of sulphated polysaccharides from marine microalgae. Mar Drugs 2013; 11(1): 233-52.
120
Carbone DA, Pellone P, Lubritto C, Ciniglia C. Evaluation of microalgae antiviral activity and their bioactive compounds. Antibiotics (Basel) 2021; 10(6): 746.
121
Kiran BR, Venkata Mohan S. Microalgal cell biofactory—therapeutic, nutraceutical and functional food applications. Plants 2021; 10(5): 836.
122
Prarthana J, Maruthi KR. Fresh water algae as a potential source of bioactive compounds for aquaculture and significance of solvent system in extraction of antimicrobials. Asian J Sci Res 2018; 12(1): 18-28.
123
Shanab SMM, Ameer MA, Fekry AM, Ghoneim AA, Shalaby EA. Corrosion resistance of magnesium alloy (AZ31E) as orthopaedic biomaterials in sodium chloride containing antioxidantly active compounds from Eichhornia crassipes. Int J Electrochem Sci 2011; 6: 3017-35.
124
Reboul E, Thap S, Perrot E, Amiot M-J, Lairon D, Borel P. Effect of the main dietary antioxidants (carotenoids, γ-tocopherol, polyphenols, and vitamin C) on α-tocopherol absorption. Eur J Clin Nutr 2007; 61(10): 1167-73.
125
Shanab SMM, Mostafa SSM, Shalaby EA, Mahmoud GI. Aqueous extracts of microalgae exhibit antioxidant and anticancer activities. Asian Pac J Trop Biomed 2012; 2(8): 608-15.
126
Jerez-Martel I, García-Poza S, Rodríguez-Martel G, Rico M, Afonso-Olivares C, Gómez-Pinchetti JL. Phenolic profile and antioxidant activity of crude extracts from microalgae and cyanobacteria strains. J Food Qual 2017; 2017: 1-8.
127
Coulombier N, Jauffrais T, Lebouvier N. Antioxidant compounds from microalgae: A review. Mar Drugs 2021; 19(10): 549-79.
128
Sansone C, Brunet C. Promises and challenges of microalgal antioxidant production. Antioxidants 2019; 8(7): 199-208.
129
Petersen HJ, Smith AM. The role of the innate immune system in granulomatous disorders. Front Immunol 2013; 4: 120.
130
Chovatiya R, Medzhitov R. Stress, inflammation, and defense of homeostasis. Mol Cell 2014; 54(2): 281-8.
131
Suh SS, Hong JM, Kim EJ, et al. Anti-inflammation and anticancer activity of ethanol extract of antarctic freshwater microalga, Micractinium sp. Int J Med Sci 2018; 15(9): 929-36.
132
Suh SS, Hong JM, Kim EJ, et al. Antarctic freshwater microalga, Chloromonas reticulata, suppresses inflammation and carcinogenesis. Int J Med Sci 2019; 16(2): 189-97.
133
Conde TA, Zabetakis I, Tsoupras A, et al. Microalgal lipid extracts have potential to modulate the inflammatory response: A critical review. Int J Mol Sci 2021; 22(18): 9825.
134
Sanjeewa KKA, Fernando IPS, Samarakoon KW, et al. Anti-inflammatory and anti-cancer activities of sterol rich fraction of cultured marine microalga Nannochloropsis oculata. Algae 2016; 31(3): 277-87.
135
Fu W, Nelson DR, Yi Z, et al. Bioactive compounds from microalgae: Current development and prospects. Studies in Natural Products Chemistry 2017; 54: 199-225.
136
Zivkovic AM, Telis N, German JB, Hammock BD. Dietary omega-3 fatty acids aid in the modulation of inflammation and metabolic health. Calif Agric 2011; 65(3): 106-11.
137
Jyotirmayee P, Sachidananda D, Basanta KD. Antibacterial activity of freshwater microalgae: A review. Afr J Pharm Pharmacol 2014; 8(32): 809-18.
138
Čermák L, Pražáková Š, Marounek M, Skřivan M, Skřivanová E. Effect of green alga Planktochlorella nurekis on selected bacteria revealed antibacterial activity in vitro. Czech J Anim Sci 2016; 60(10): 427-35.
139
Potocki L, Oklejewicz B, Kuna E, Szpyrka E, Duda M, Zuczek J. Application of green algal Planktochlorella nurekis biomasses to modulate growth of selected microbial species. Molecules 2021; 26(13): 4038.
140
Najdenski HM, Gigova LG, Iliev II, et al. Antibacterial and antifungal activities of selected microalgae and cyanobacteria. Int J Food Sci Technol 2013; 48(7): 1533-40.
141
Falaise C, François C, Travers MA, et al. Antimicrobial compounds from eukaryotic microalgae against human pathogens and diseases in aquaculture charlotte. Mar Drugs 2016; 14(9): 159.
142
Little SM, Senhorinho GNA, Saleh M, Basiliko N, Scott JA. Antibacterial compounds in green microalgae from extreme environments: a review. Algae 2021; 36(1): 61-72.
143
Noel VT, Dlzar DG, A SMD, Rawa RI, Lanya KJ. Antibacterial effects of the organic crude extracts of freshwater algae of Sulaymaniyah, Kurdistan Region, Iraq. J Med Plants Res 2021; 15(4): 178-87.
144
Alsenani F, Tupally KR, Chua ET, et al. Evaluation of microalgae and cyanobacteria as potential sources of antimicrobial compounds. Saudi Pharm J 2020; 28(12): 1834-41.
145
Abdo SM, Hetta MH, El-Senousy WM, El Din Salah RA, Ali GH. Antiviral activity of freshwater algae. J Appl Pharm Sci 2012; 02: 21-5.
146
Ayehunie S, Belay A, Baba TW, Ruprecht RM. Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis). J Acquir Immune Defic Syndr Hum Retrovirol 1998; 18(1): 7-12.
147
Chirasuwan N, Chaiklahan R, Kittakoop P, et al. Anti HSV-1 activity of sulphoquinovosyl diacylglycerol isolated from Spirulina platensis. Sci Asia 2009; 35(2): 137-41.
148
Reynolds D, Huesemann M, Edmundson S, et al. Viral inhibitors derived from macroalgae, microalgae, and cyanobacteria: A review of antiviral potential throughout pathogenesis. Algal Res 2021; 57102331
149
Santoyo S, Jaime L, Plaza M, et al. Antiviral compounds obtained from microalgae commonly used as carotenoid sources. J Appl Phycol 2012; 24(4): 731-41.
150
Mahendran MS, Djearamane S, Wong LS, Kasivelu G, Dhanapal ACTA, Dhanapal A. Antiviral properties of microalgae and cyanobacteria. J Exp Biol Agric Sci 2021; 9(Spl-1- GCSGD_2020): S43-8.
151
Chirasuwan N, Ratana C, Marasri R, Boosya B, Morakot T. Anti HSV-1 activity of Spirulina platensis polysaccharide. Kasetsart J 2007; 41: 311-8.
152
Skjånes K, Aesoy R, Herfindal L, Skomedal H. Bioactive peptides from microalgae: Focus on anti-cancer and immunomodulating activity. Physiol Plant 2021; 173(2): 612-23.
153
Sheih IC, Fang TJ, Wu TK, Lin PH. Anticancer and antioxidant activities of the peptide fraction from algae protein waste. J Agric Food Chem 2010; 58(2): 1202-7.
154
Tavares-Carreón F, De la Torre-Zavala S, Arocha-Garza HF, Souza V, Galán-Wong LJ, Avilés-Arnaut H. In vitro anticancer activity of methanolic extract of Granulocystopsis sp., a microalgae from an oligotrophic oasis in the Chihuahuan desert. PeerJ 2020; 8e8686
155
El-fayoumy EA, Shanab SMM, Gaballa HS, Tantawy MA, Shalaby EA. Evaluation of antioxidant and anticancer activity of crude extract and different fractions of Chlorella vulgaris axenic culture grown under various concentrations of copper ions. BMC Complementary Medicine and Therapies 2021; 21(1): 51.
156
Chothiphirat A, Nittayaboon K, Kanokwiroon K, Srisawat T, Navakanitworakul R. Anticancer potential of fruit extracts from vatica diospyroides symington type ss and their effect on program cell death of cervical cancer cell lines. ScientificWorldJournal 2019; 2019: 1-9.
157
Bule MH, Ahmed I, Maqbool F, Bilal M, Iqbal HMN. Microalgae as a source of high-value bioactive compounds. Front Biosci (Schol Ed) 2018; 10(2): 197-216.
158
Saadaoui I, Rasheed R, Abdulrahman N, et al. Algae-derived bioactive compounds with anti-lung cancer potential. Mar Drugs 2020; 18(4): 197.
159
Karan T, Aydin A. Anticancer potential and cytotoxic effect of some freshwater cyanobacteria. Trop J Pharm Res 2019; 17(11): 2183-8.
160
Luesch H, Yoshida WY, Moore RE, Paul VJ, Corbett TH. Total structure determination of apratoxin A, a potent novel cytotoxin from the marine cyanobacterium Lyngbya majuscula. J Am Chem Soc 2001; 123(23): 5418-23.