Review articleThe cosmetic application of cyanobacterial secondary metabolites
Introduction
Skin is a complex organ that acts as a physical barrier against water loss and environmental factors, including solar UV radiation, chemicals, pathogens, and physical agents [1]. Skin provides necessary physiological functions, such as thermoregulation, sensory input from mechanoreceptors, immune defence, and endocrine and metabolic mechanisms to maintain optimal health. However, intrinsic (genetic) and extrinsic (UV radiation, pollution, etc.) mechanisms induce multiple changes such as dryness, fragility of structural proteins (for example, type-1 collagen), fine lines, and wrinkles in the dermal layer of skin that eventually lead to skin ageing [2].
Photo-ageing is the most damaging phenomenon for the skin as the result of chronic and unprotected exposure to UV radiation, oxidative stress, the induction of proinflammatory genes, infectious agents that alter the DNA, and pollution [1,3]. In addition, the increase of reactive oxygen species (ROS), that is produced during the oxidative cell metabolism, plays a major role in damaging cell walls, mitochondria, lipid membranes, and DNA. Molecular mechanisms of skin ageing can induce an inflammatory response, and stimulate mitogen-activated protein kinases involved in the phosphorilation of transcription factor activator protein 1 (AP-1) which, in turn, results in the upregulation of matrix metalloproteinases that are contributing to the degradation of skin collagen and connective tissue. In this regard, for instance, mycosporine-like amino acids (MAAs) are natural compounds that are found in a wide variety of organisms, including cyanobacteria and macroalgae and, owing to their positive effects on cell regeneration which are observed in human skin fibroblasts, MAAs appear to be potential cosmetic agents [1,4].
Such bioactive substances which are derived from natural products are currently a priority goal of the cosmetics industry [5,6]. Natural products are comprised of large amounts of antioxidants and beneficial metabolites for cosmetic applications, besides their low toxicity level [[7], [8], [9], [10]]. In particular, microalgae are one of the main natural sources of metabolites that are potentially beneficial in cosmetics, and it has been found that some microalgae extracts can accelerate the healing and repairing process of damaged skin and that also have anti-blemish and anti-inflammatory effects [1,11,12]. Nostoc, Spirulina (Arthrospira), and Aphanizomenon are the most specifically studied cyanobacterial species in this regard [13], because they contain substantial amounts of calcium, beta-carotene, phosphorous, iron, biotin, folic acid, pantothenic acid and vitamin B12, and the application of these cyanobacterial extracts and bioactive compounds in cosmetics for skin and hair protection is a current research goal [14]. For example, beta-carotene that is extracted from Desmonostoc muscorum, Leptolyngbya foveolarum and Arthrospira platensis can regulate UV-A radiaton-induced gene expression in human keratinocytes [15], and the modulation of various biological targets, such as NF-κB, COX-2, and matrix metalloproteinase-9 can be attributed to its anti-inflammatory activity [1]. Cyanobacterial phycobiliproteins (PBPs), such as phycocyanin (PC), have also demonstrated antioxidant anti-inflammatory activities [6,16] and they have been applied in cosmetics as antioxidants, anti-inflammatory agents, and anti-ageing agents [12,16,17].
Cyanobacteria are phylogenetically coherent Gram-negative prokaryotes with numerous advantages that make them a potential option for cosmetic applications:
- a)
Cyanobacteria have basic nutritional requirements: certain cyanobacterial strains (Nostoc punctiforme, Anabaena, Tolypothrix, Aulosira) are able to fix the atmospheric nitrogen sources (N2, NO3− or NH4+) into organic nitrogen-containing compounds, such as scytonemin [5,[18], [19], [20]]. They are one of the primigenial photo-synthesizers on the planet, performing the oxygenic photosynthesis in a similar way to terrestrial plants but with different quantum yield values (0.4 vs. 0.8 in higher plants [21]) and higher photosynthesis and biomass production rates (up to 3–9% of the solar energy that is converted into biomass compared to ≤0.25–3% that is achieved by crops). They also require less land area for cultivation than terrestrial plants, thus reducing the competition for arable land with crops that are intended for human consumption [22].
- b)
Cyanobacteria are comprised of 150 genera and >2000 species and they exhibit a broad morphological diversity which ranges from simple unicellular and colonial to complex, filamentous species, covering also a wide spectrum of physiological properties. These characteristics allow them to tolerate extreme environmental conditions [5].
- c)
Cyanobacteria grow in a variety of habitats, including aquatic and terrestrial environments, or even in symbiosis with other organisms [3,6]. Therefore, they are chronically exposed to extreme conditions concerning light intensity, temperature, pH and salinity levels [11]. When adapting to these extreme conditions, cyanobacteria produce a broad diversity of biologically active secondary metabolites, including carotenoids, essential fatty acids, polysaccharides, PBPs (PC mostly), amino acids, minerals, and a number of photo-protective components such as scytonemins and MAAs [1]. These compounds can be used in cosmetics for sun protection and water-binding applications as well as anti-ageing agents in creams, refreshing agents in daily care products, and emollient and anti-irritant factors in peelers [1]. In total, >300 nitrogen-containing secondary metabolites with various structural types have been discovered in cyanobacteria, with most of them being active metabolites that are produced through the nonribosomal polypeptide (NRP) or the mixed polyketide-NRP biosynthetic pathways [5,23,24]. It has been suggested that manipulating cyanobacteria growth conditions through the induction of different types of stresses may actually promote the levels of pharmaceutically active biocompounds [[25], [26], [27]].
The production of secondary metabolites in cyanobacteria is a two-step process. First, cultures are provided with optimal conditions to promote growth. Then, various stress factors such as nutrient deprivation or high light intensities are applied to maximise the production rate of secondary metabolites with desired pharmaceutical or antioxidant properties [26]. In large scale production, flat-plate reactors, membrane photo-bioreactors and different tubular reactors with airlift systems (horizontal, vertical or helicoidal) are widely used to enhance biomass compositions and also for harvesting useful biomolecules [3,28].
Section snippets
Potential of cyanobacteria as a sunscreen
UV radiation is a major environmental stressor that promotes the accumulation of reactive oxygen species (ROS), thus enforcing several clinical manifestations in the skin. Short-term UV radiation exposures such as sunburn can lead to chronic reactions including premature skin ageing and benign or malignant skin cancers, such as melanoma [18]. UV-A radiation (320–400 nm) is an intense component that penetrates the dermis where ageing changes such as pigment abnormalities, dryness or wrinkling [18
Cyanobacteria as moisturising agent
Water is responsible for the normal functioning, elasticity, maturation and desquamation of skin, particularly in the outer layers, hence water is the most critical component of skin. Environmental factors put the skin under chronic desiccation stresses, resulting in a reduction in flexibility with physical manifestations, such as itchiness, redness, cracks, flaky appearance and eczema [66]. In cases of atopic dermatitis, dry skin conditions, or alterations of the filagrin gene, that forms the
Cyanobacteria as antioxidants
Genetic factors, excessive exposure to solar irradiation, pollutants and high stress levels, as well as alcohol and smoking abuse, stimulate oxidative stress in tissues by generating massive amounts of free radicals called ROS. Singlet oxygen (O2), superoxide radical (O2−), hydroxyl radical (OH−) and hydrogen peroxide (H2O2) are different types of ROS that are constantly produced in the cells as a result of their metabolism. Oxidative stress causes premature ageing, wrinkles, and inflammations,
Cyanobacteria as antiaging systems
Skin ageing is a slow and complex process that leads to many changes in the texture of skin, such as thinning, dryness, laxity, fragility, enlarged pores, fine lines, and wrinkles. Progerin accumulates over time as the skin ages, and works with telomeres to trigger cellular senescence in normal human fibroblasts [94]. Environmental factors, such as exposure to heavy metals, UV radiation and pollution, increase the level of ROS in those regions. ROS are the most common reasons for skin ageing,
Natural colourants for cosmetics
Cyanobacterial PBPs have commercial uses as natural cosmetic ingredients. PBPs are hydrophilic proteins that are bonded to phycobilins, which are photosynthetic pigments, and they are mainly found in cyanobacteria and some red algae [99]. These metabolites have a structural resemblance to bilirubin, which is known to be an effective quencher of different oxygen derivatives [28,98], and it has been suggested that PBPs could be good antioxidant agents [100]. These highly fluorescent
Cyanobacteria as anti-inflammation agents
Many cyanobacteria-derived compounds exhibit anti-inflammatory properties, e.g. a wide range of terpenoid-type compounds such as carotenoids and phytols, essential for chlorophyll, quinone prenyl tails, hormones and tocopherols, are biosynthesised through the methylerythritol 4-phosphate pathway in cyanobacteria and algae. Phytol serves as an anti-inflammatory agent [119,120] and scytonemin (a photoprotective compound that is isolated from Scytonema) has a unique pharmacological potential as an
Availability of natural resources for use in cosmetics
There are certain optimal cultivation conditions for maximising the production rate of secondary metabolites in extremophilous cyanobacteria. According to multiple studies [42,55,142], the accumulation of MAAs depends on factors such as UV radiation, salinity, temperature and nutrient availability. For example, in Trichormus variabilis the synthesis of shinorine can be induced by adding sulphur, ammonium and magnesium [42,142], and blue light, UV-A and UV-B also increase MAA synthesis [143],
Control of the production of bioactive compounds in cyanobacteria
The first known use of cyanobacteria by humans dates back to 2000 years ago by the Chinese who used Nostoc for survival during famine. However, cyanobacteria biotechnology only began to develop in the 1950s and nowadays there are numerous commercial applications of these organisms, e.g. to enhance the nutritional value of food and animal feed, owing to their chemical composition. Further, they play a crucial role in aquaculture and their products can be incorporated into cosmetics [161,162]. In
Conclusions and perspectives
The growing economy of the cosmetic industry requires safer and more efficient natural raw ingredients. According to different studies that are summarised in this paper, cyanobacteria are potentially useful sources of natural bioactive compounds for the cosmetic industry. Metabolites, such as MAAs, pigments and proteins, can enhance skin health by acting as anti-ageing (collagen boosting) or anti-inflammatory agents. Extracts obtained from these microorganisms can be exploited as UV
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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