The Potential of Algae in the Nutricosmetic Sector

Seaweeds or algae are marine autotrophic organisms. They produce nutrients (e.g., proteins, carbohydrates, etc.) essential for the survival of living organisms as they participate in biochemical processes and non-nutritive molecules (such as dietary fibers and secondary metabolites), which can improve their physiological functions. Seaweed polysaccharides, fatty acids, peptides, terpenoids, pigments, and polyphenols have biological properties that can be used to develop food supplements and nutricosmetic products as they can act as antibacterial, antiviral, antioxidant, and anti-inflammatory compounds. This review examines the (primary and secondary) metabolites produced by algae, the most recent evidence of their effect on human health conditions, with particular attention to what concerns the skin and hair’s well-being. It also evaluates the industrial potential of recovering these metabolites from biomass produced by algae used to clean wastewater. The results demonstrate that algae can be considered a natural source of bioactive molecules for well-being formulations. The primary and secondary metabolites’ upcycling can be an exciting opportunity to safeguard the planet (promoting a circular economy) and, at the same time, obtain low-cost bioactive molecules for the food, cosmetic, and pharmaceutical industries from low-cost, raw, and renewable materials. Today’s lack of methodologies for recovering bioactive molecules in large-scale processes limits practical realization.


Introduction
The main goal of the Circular Economy is to reuse and recycle natural resources to minimize health, energy, and environmental impacts. The European citizen produces around 5 tonnes of waste, much of which finishes in incinerators or landfills, and a little is recycled [1]. Waste management policies have been investigated to avoid landfills and allow the recovery of renewable energy and recycled materials [2]. Organizations have developed circular waste management systems, promoting resource flow and enhancing product sustainability and processes [3]. Consumption of eco-friendly products and decreasing waste are crucial to achieving the European sustainable goals. Ten megatrends were recognized for 2022 by New Nutrition Business for food, nutrition, and health. Sustainability came fifth [4]. Representative population surveys indicate that many people (amongst them young consumers) wish to contribute to sustainable development [5][6][7][8][9][10]. Buying eco-friendly products is considered one way to intervene. In the European Union, 26% of consumers purchase eco-friendly products, and 54% rarely use such items [11]. The global market value of natural and organic skincare products will probably grow from 9.9 billion dollars in 2021 to 20.4 billion dollars by 2030 [12]. The organic segment (made from plant ingredients that have been grown in soil free of fungicides, pesticides, synthetic fertilizers, and herbicides, and genetically modified organisms) was valued at $28,323.2 million in 2021 and is expected to reach $74,058.5 million by (CAGR of 9.8%) [13]. This data supports the significant contribution of the cosmetics market worldwide to environmental sustainability. The seaweed waste (e.g., beach-casts) [14] and invasive species valorization [15], which are of no commercial value and must be disposed of in landfills, type and species), external factors (i.e., water temperature, water composition, salinity gradient, time of year, organism age), and cultivation conditions such as size and type of cultivation reactor [39]. During stress conditions, algae produce organic phenolic and phlorotannin and improve the uptake of inorganic ions to protect them from UV lights and desiccation. [40]. The wave exposure, environmental gradients, and algae reproductive cycles affect carbohydrate profile and content [41]. Chemicals (e.g., pH, carbon dioxide, salinity mixing/aeration), physical parameters (e.g., light, radiation, temperature), carbon sources (e.g., organic carbon like sugars and CO2), nitrogen, salts, phosphorous, and vitamins affect the algaes' growth [42]. Microalgae can be grown autotrophically, heterotrophically, and mixotrophically. Cellular self-shading and low light availability negatively affect biomass production during autotrophic nutrition. Inorganic carbon sources can enhance biomass concentration and photosynthetic activities [42]. Organic substrates such as sugars, organic acids, etc. (heterotrophic nutrition), give rapid growth, low harvesting costs, and high biomass production [43]. The high cost of organic carbon sources, substrate inhibition, contamination, and the low number of microalgal species that can be grown in this way limit heterotrophic nutrition [44]. Mixotrophic algae can photosynthesize, assimilate, and metabolize organic carbon and are less dependent on light penetration for higher cell densities than autotrophy ones. During dark respiration, they manage biomass decrease, using lower organic substrate amounts than heterotrophic growth and enhancing the synthesis of the PUFA (polyunsaturated fatty acids) [44][45][46]. Algae can improve air quality by fixing CO2 [47] (they are responsible for 50% of the photosynthesis on earth) [48] and are an alternative source of bioenergy production since they produce biofuels [49]. Finally, they can reduce pollution [50] by converting water and CO2 into organic matter [51].

Polysaccharides
Marine macroalgae are good carbohydrate sources (mainly polysaccharides and low concentration of disaccharides and monosaccharides) whose content is from 5 to 75% (w/w, DW) based on the age, period, species, and harvesting site [52,53]. Polysaccharides in seaweeds can be sulfated and non-sulfated [54]. They constitute the algae cell walls and are species-specific ( Figure 2)

Proteins and Derivatives
Seaweeds are a rich source of proteins (in single or conjugate form) and protein derivatives (e.g., free amino acids and peptides) [23]. Red algae have the highest proteins and derivative contents (up to 47%), green algae have medium levels (between 9-26%), and brown algae contain the lowest concentrations (3-15%) [114]. Protein and bioactive peptides have high antioxidant, anti-inflammatory, skin proactive, and antiaging properties [115][116][117]. Pedoclimatic conditions affect the proteins, peptides, and amino acids contents in algae.

Phenolics
Phenolic compounds are secondary plant metabolites with one or more aromatic rings with one or more -OH phenolic groups (e.g., phlorotannins, bromophenols, flavonoids, phenolic terpenoid, and mycosporine-like amino acids) [130]. They can defend algae from pedoclimatic injuries and parasite attacks [131,132]. The biological activities attributed to the algae's phenolic compounds are summarized in Figure 4 [133].
Dioxinodehydroeckol from Ecklonia cava and fucofuroeckol-A derived from the brown seaweed Ecklonia stolonifera Okamura can protect against UVB radiation [164,165].
Chlorophylls are characterized for containing a porphyrin ring with a central magnesium ion. They protect algae against oxidative stress due to UV radiation [218].
The phycocyanin R-phycoerythrin and allophycocyanin are employed as colorants in cosmetic formulations [220].
Algae terpenoids, sulfur compounds, fatty acids, and carotenoids can be employed as flavoring in cosmetic, food, and nutraceutical formulations [230,231].

Food and cosmetic antimicrobial and antifungals
•Phlorotannins •Terpenoids Algae polysaccharides can be employed for their rheological behavior. Carrageenan, agar, and alginate can be used for gelling, emulsifying, stabilizing, and thickening since they form highly viscous solutions in water [232,233].
They are GRAS substances considered safe for human consumption by the European Food Safety Authority and the Food and Drug Administration [234]. The fucoidan (from U. pinnatifida and F. vesiculosus) was authorized by the European Commission (Regulation 2017/2470) in foods and food supplements [235]. The algal phlorotannins, peptides, and polysaccharides can protect the nutricosmetic formulation's lipidic component from oxidative deterioration and maintain their original sensorial properties [236][237][238]. Finally, algae's terpenoids and phlorotannins can be employed as preservative agents against bacteria and fungi [239].

Cosmetic Potenziality of Algae Metabolites
Algae's metabolites in nutricosmetic products can be used as moisturizing, antiaging, skin whitening, anti-cellulite, and slimming care agents (Figure 8).

Algae Metabolites in Moisturizing Formulations
The skin protects the body from the environment by maintaining an efficient epidermal barrier against injuries and preventing excessive water loss. The Natural Moisturizing Factors (NMF) present in the Stratum corneum, the epidermis' outermost layer, contain lactic acid, pyrrolidone carboxylic acid urea, and amino acids (e.g., serine) able to uptake water [240]. The fat metabolism (in sebaceous glands) and conversion of phospholipids to free fatty acids produce glycerol [241] transported by the aquaporins through the epidermis via specific water/glycerol channels. Aquaporin expression is stimulated by retinoic acid [242].
They are GRAS substances considered safe for human consumption by the European Food Safety Authority and the Food and Drug Administration [234]. The fucoidan (from U. pinnatifida and F. vesiculosus) was authorized by the European Commission (Regulation 2017/2470) in foods and food supplements [235]. The algal phlorotannins, peptides, and polysaccharides can protect the nutricosmetic formulation's lipidic component from oxidative deterioration and maintain their original sensorial properties [236][237][238]. Finally, algae's terpenoids and phlorotannins can be employed as preservative agents against bacteria and fungi [239].

Cosmetic Potenziality of Algae Metabolites
Algae's metabolites in nutricosmetic products can be used as moisturizing, antiaging, skin whitening, anti-cellulite, and slimming care agents (Figure 8).

Algae Metabolites in Moisturizing Formulations
The skin protects the body from the environment by maintaining an efficient epidermal barrier against injuries and preventing excessive water loss. The Natural Moisturizing Factors (NMF) present in the Stratum corneum, the epidermis' outermost layer, contain lactic acid, pyrrolidone carboxylic acid urea, and amino acids (e.g., serine) able to uptake water [240]. The fat metabolism (in sebaceous glands) and conversion of phospholipids to free fatty acids produce glycerol [241]   Cosmetic products for dehydrated skin are based on ingredients with film-forming and occlusive properties (e.g., vegetable oils, fatty alcohols, hydrocarbons, waxes, silicones, and butter, etc.), or humectant agents, (which improve the Stratum corneum ability to capture water, e.g., glycerin or propylene glycol) [243] or moisturizers that penetrate the corneous layer permitting water to be retained [244].
The algae's polysaccharides (mainly made by green and brown algae), oligosaccharides, and fatty acids can be employed as moisturizing agents. The polysaccharides (mainly marine green algae) moisturize slower and retain more moisture than glycerin [245]. A moisturizing retention rate of over 94% was referred to the polysaccharides belonging to brown algae (e.g., Sargassum horneri [246], Sargassum vachellianum [247], Sargassum hemiphyllum [248]. When applied topically, the sulfated polysaccharides (from red algae Porphyra haitanensis) enhance dry facial skin features and moisturization, regulating the keratinized envelope's maturation of the stratum corneum and dermal-epidermal junction [245]. Low molecular weight and sulfated group enhance the moisture-retention and absorption abilities [192]. The alginates (extracted from brown macroalgae) and agar (from red macroalgae) have hydrating properties linked to their ability to conserve water [249].
The lipids can maintain skin integrity and purity, restoring barrier permeability and preventing skin dehydration due to unsaturated fatty acid deficiency in the skin. The brown macroalgae Laminaria ochroleuca produces numerous unsaturated fatty acids (e.g., oleic acid, linoleic acid, linolenic acid, and palmitoleic acid) with moisturizing properties widely used in oil/water emulsions to maintain water loss in the skin [250]. Oral or topical administration of astaxanthin (carotenoid) can improve skin moisture by improving the aquaporin levels (substances that regulate skin moisture and function) [251]. The green microalga Cladophora glomerata contains unsaturated fatty acids C16:1 (n-7) and C18:1 (n-3) and saturated fatty acids (palmitic acid C16:0) that can be used as emollients and to reduce water loss, and sulfated polysaccharides that have moisturizing properties [252].

Algae Metabolites in Antiaging Formulations
During the aging process, the dermis change. The matrix metalloproteinases (MMPs) activity increases, and collagen (one of the significant components of the extracellular matrix) levels decline [253]. Intrinsic (natural skin degradation) and extrinsic (ROS generated by UV radiation, pollution, etc.) factors can cause dryness, thinning, laxity, enlarged pores, fragility, wrinkles, and fine lines. The bioactive molecules that inhibit metalloproteinases help constrain aging. Sulfated polysaccharides (found in Phaeophyceae, Rhodophyceae, and Chlorophyceae), and polyphenols, derived from phloroglucinol, downregulate the metalloproteinases activity [254,255]. Fucoidan can regulate fibroblasts and restore skin tissue function [256]. Carrageenans act as thickening, water-binding [257] antioxidant, and antiphotoaging bioactive molecules [258]. Galactan of P. haitanensis decreases the cell's aging process regulating the p53-p21 signaling pathway [259]. Astaxanthin (a carotenoid) protect against photo-oxidation [215]. Fucoxanthin upregulates the fibroblasts' procollagen synthesis and decreases the expression of matrix metalloproteinases in wrinkle care cosmetics [260]. Amino acids and peptides from macroalgae stimulate collagen production in the skin [219]. Mycosporine-like amino acids act as antioxidants, antiinflammatories, UV-absorbing agents, and down-regulate the protein-glycation and collagenase activity [126]. Ascorbyl palmitate antioxidant effect is used in anti-aging and anti-wrinkle formulations [261,262].

Algae Metabolites in Skin Whitening Formulations
The pigmentation process controls the color of mammalians' hair, skin, and eyes [263]. Tyrosinase enzyme regulates the conversion of L-tyrosine and L-3,4-dihydroxyphenylalanine (L-DOPA) in pheomelanin (red-orange pigment) and eumelanins (dark brown pigments) [264,265]. When tyrosinase is upregulated, hyperpigmentation determines freckles, age spots, irregular dark patches, and nevi. On the contrary, when tyrosinase is downregulated, melanin synthesis is reduced, and white patches (e.g., vitiligo) are observed [266]. Some algae's phenols, terpenoids, amino acids, sugars, and amines, used as skin-whitening agents, are tyrosinase inhibitors [192,267]. Red algae, the richest sources of mycosporine-like amino acids, are a helpful source of whitening bioactive molecules for the cosmeceutical industry [268].

Algae Metabolites in Anticellulite and Slimming Care Formulations
In cosmetology, the term "slimming product" is preferred to "anti-cellulite" since cellulite is a disorder produced by a deep dermis and subcutaneous tissue change and, therefore, a term linked to the medical world [269]. Cellulite has a multifactorial etiology [270]. Estrogens and microcirculation disorders (decreasing blood flow in the capillaries), the nervous system (downregulating the lipolysis process), and genetic factors can be involved. The slimming product objectives include correcting the" orange peel" appearance and "mattress symptom" characterized by roughness, skin surface collapse, and yellow-gray skin tone.
The iodine-rich algae (e.g., Laminaria Japonica) can be used to constrain cellulite since iodine regulates the thyroid hormones' synthesis, which boosts lipolysis by facilitating the penetration of fatty acids into the mitochondria [192,271,272].
Examples of patents claiming the use of algae and algae metabolites in cosmetic formulations are reported in Table 1. Marine extracts and biofermentations for use in cosmetics [276] CN105777933A Preparation of algal polysaccharides and application of algal polysaccharides in cosmetics [277] TW200914061A Method for using green algae extract to retard aging of skin cells and cosmetic composition containing green algae extract [278]

Macroalgae Biomass in a Circular Economy Perspective
Recent studies have considered algae a sustainable and environmentally friendly way to eliminate contamination from wastewater since they use low energy and pollutants to grow [282] and to produce biomass [283]. The dry biomass or wet paste of microalgae can be employed to extract bioactive metabolites. Selling prices improve from biomass to secondary metabolites [284]. The "chemicals and materials" and bio-energy market use whole biomass. The "food, pharmaceuticals and personal care" markets employ primary and secondary metabolites in the feed, food, supplement, nutraceutical, and cosmeceutical preparations. Raw biomass can enhance the soil organic matter and water capacity in agriculture. The defatted biomass from biodiesel extraction, mixed with water, can produce biogas after anaerobic digestion and can be used to extract metabolites. For example, the residual lipids can be upcycled as supplements in animal feed [285]. Glycerol, a byproduct of the microalgal lipids' transesterification to biodiesel, can be converted to solvents, polymers, and aliphatic polyesters, to generate electricity directly in biofuels cells or to prepare foods, cosmetics, and drugs [286]. The digestate resulting from biogas production can be employed as fertilizer and conditioner. Microalgae biomass can be employed as a food supplement, feed additive, and feed in the aquaculture of crustaceans, fishes, and mollusks [287]. Proteins, lipids (e.g., phospholipids and glycolipids), starches, and sugars can be used in food, nutraceutical and personal care, and drug products. Chlorophylls and carotenoids can be used as food and cosmetic dyes [288]. Sterols can be used as antiinflammatory and cholesterol-lowering bioactive molecules in foods and supplements [289]. PUFA and oxylipins can be used as nutricosmetics, food supplements, and feeds [290,291]. The cost, microbial and chemical contaminants' accumulation, and the lack of technology viable for large-scale applications give a setback to algal wastewater treatments [292]. Different is the speech of the potential use of the beach-cast macroalgae. Tonnes of marine algae are removed per year and dumped in landfills. Very few registers of abundance and composition of beach-cast marine algae worldwide exist. These algae should be less rich in toxic products than algal wastewater and probably do not need detoxification processes [293]. Thus, it would be enough to imagine strategies for large-scale extraction of bioactive molecules to take advantage of this natural and eco-sustainable source of raw materials for industry.

Conclusions
Algae are rich sources of bioactive molecules (amino acids, carbohydrates, lipids, phenols, and terpenoids), helpful for improving the functional, stability, and sensorial characteristics of nutricosmetic products. The vast array of bioactive molecules makes algae an attractive and versatile resource to obtain safe bio-based products. Algae extract and their purified metabolites are gaining increasing commercial importance. Many patents concerning algae extracts or metabolites application in nutricosmetic products have been registered recently. Unfortunately, many do not report the mechanisms responsible for cosmetic performance. It would be helpful that more works evaluate the algae extract profiles to identify functional properties, stability, compatibility, and toxicology aspects to facilitate the development of new nutricosmetic. Concerning the use of algae to eliminate pollution from wastewater and produce biomass from which obtain bioactive molecules, the cost, non-sterile conditions, and lack of technology viable for large-scale applications limit their application. Better potential can be seen for the recycling of beach-cast macroalgae.