Skincare application of medicinal plant polysaccharides — A review

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Skincare application of medicinal plant polysaccharides — A review

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Polysaccharides are macromolecules with important inherent properties and potential biotechnological applications. These complex carbohydrates exist throughout nature, especially in plants, from which they can be obtained with high yields.

Carbohydrate Polymers 277 (2022) 118824 Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol Review Skincare application of medicinal plant polysaccharides — A review Priscilla Barbosa Sales Albuquerque a, Weslley Felix de Oliveira b, Priscila Marcelino dos Santos Silva b, Maria Tereza dos Santos Correia b, John F Kennedy c, Luana Cassandra Breitenbach Barroso Coelho b, * a Departamento de Medicina, Universidade de Pernambuco, R Capit˜ ao Pedro Rodrigues, 105 - S˜ ao Jos´e, CEP 55.295-110 Garanhuns, PE, Brazil Departamento de Bioquímica, Centro de Biociˆencias, Universidade Federal de Pernambuco, Av Prof Moraes Rego, 1235 - Cidade Universit´ aria, CEP 50.670-901 Recife, PE, Brazil c Chembiotech Research, Tenbury Wells WR15 8FF, Worcestershire, United Kingdom b A R T I C L E I N F O A B S T R A C T Keywords: Medicinal plant polysaccharides Wound healing Antimicrobial properties Antioxidant action Antitumoral activity Hydration Polysaccharides are macromolecules with important inherent properties and potential biotechnological appli­ cations These complex carbohydrates exist throughout nature, especially in plants, from which they can be obtained with high yields Different extraction and purification methods may affect the structure of poly­ saccharides and, due to the close relationship between structure and function, modify their biological activities One of the possible applications of these polysaccharides is acting on the skin, which is the largest organ in the human body and can be aged by intrinsic and extrinsic processes Skincare has been gaining worldwide attention not only to prevent diseases but also to promote rejuvenation in aesthetic treatments In this review, we discussed the polysaccharides obtained from plants and their innovative potential for skin applications, for example as wound-healing, antimicrobial, antioxidant and anti-inflammatory, antitumoral, and anti-aging compounds Introduction The skin is the largest organ of the human body Due to this extensive area, it is commonly exposed to a range of noxious agents and sun damage that may lead to dehydration, wounds, microbial invasion, and even skin carcinogenesis over the long term (Oli et al., 2017; Zegarska et al., 2017) In addition to the pathological processes that affect the skin, its inevitable senescence, which can happen physiologically and be enhanced by environmental agents (Ho & Dreesen, 2021), is still a concern for many people, driving new research in the area of aesthetics Different strategies to treat the phenotypic signs of aging skin by intrinsic and extrinsic mechanisms have been used, such as invasive procedures and the use of chemical agents topically or systemically (Zouboulis et al., 2019) Thus, many works in the literature have explored remarkable applications of well-known polysaccharides, including those able to protect the skin against damage However, new sources of these polymers are needed because of the recent interest of the industry to prefer natural products over synthetic ones Over the years, humans have obtained several products essential to their existence from nature; the exploitation of raw materials, most of them macromolecules of organic origin, supports the well-being, development, and comfort of society Such products, namely bio­ polymers, are high molecular-weight macromolecules classified ac­ cording to their source, structure, and composition of monomeric units, including groups of proteins, lipids/surfactants, polyphenols, polyesters, and polysaccharides In this review, special attention will be given to polysaccharides Polysaccharides can be extracted from plants, algae, animals, fungi, or obtained via fermentation, and are submitted to sequential steps of extraction, separation, and purification Polysaccharides derived from plants are part of the history of herbal ingredients and have been the most exploited due to their benefits towards human health Terrestrial medicinal plants recorded in ‘Chinese Herbal’ of Traditional Chinese Medicine, Ayurvedic Medicine in India (considered the Mother of Medicine), and National Medicine in Brazil have a very long history since ancient times, using different parts of the plants (fruits, seeds, roots, leaves, and flowers) for internal or external applications (Delattre, Fenoradosoa, & Michaud, 2011; Liu et al., 2020) Naturally occurring polysaccharides show distinct structural fea­ tures, including their molecular weight, monosaccharide composition, charge properties, and glycosidic linkages, which determine their functional properties and contribute to their extensive applications * Corresponding author E-mail address: lcbbcoelho@gmail.com (L.C.B.B Coelho) https://doi.org/10.1016/j.carbpol.2021.118824 Received 26 June 2021; Received in revised form 29 September 2021; Accepted 25 October 2021 Available online 28 October 2021 0144-8617/© 2021 Elsevier Ltd This article is made available under the Elsevier license (http://www.elsevier.com/open-access/userlicense/1.0/) P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 Based on their function, shape and chemical nature, polysaccharides can be classified as homopolysaccharides or heteropolysaccharides, with storage or structural functions, and of a charged (acidic and basic) or non-charged (neutral) nature The complex structure of these macro­ molecules is unstable in both acidic or basic conditions and also at high temperatures, which contributes to oxidative reactions and degradative processes (Yuan et al., 2020) Thus, some structural features of polysaccharides can be unfavorable for bioactivities In order to solve these problems, some methods have been employed to modify the structure of polysaccharides Modifica­ tions in the chemical nature of polysaccharides directly affect their biological activities Given this problem, scientific advances have pro­ posed a few strategies to circumvent the issues associated with the instability of polysaccharides, in addition to proving their biological significance as parts of proteins and nucleic acids (Liu et al., 2020) The current understanding of the biological activities of polysaccharides highlights antioxidant, antimicrobial, anticancer, healing, antiviral, immunomodulatory, antidiabetic, anticoagulant, insecticidal, hypolipi­ demic, antiparasitic, and radioprotective effects It is important to mention that we observed a great increment in the number of publica­ tions considering the antiviral activity of polysaccharides produced by bacteria and fungi (land and sea) and their sulfated derivatives from March 2020 to now, reaching values almost 50% higher than the number of publications before December 2019; for sure the urgent sit­ uation of the Coronavirus pandemic has stimulated this significant growth Beyond their medicinal value and the extensively exploitation in the pharmaceutical and biomedical industries, polysaccharides have been studied on industrial scales for foodstuffs, oil well drilling, textiles, and paper and electrical insulation They can be molded as blends, hydro­ gels, coatings, filmogenic solutions, wound dressings, and matrices for controlled drug release; even in different formulations, polysaccharides are considered to be superior to other polymers for their ease in tailoring, biocompatibility, bioactivity, homogeneity, and bioadhesive properties (Gopinath, Saravanan, Al-Maleki, Ramesh, & Vadivelu, 2018) The use of polysaccharides for skin applications has been gaining more attention in recent years because they achieve potent efficacy against dehydration, aging, microbial infections, and skin cancer Therefore, this work catalogs the latest advances in the topic of poly­ saccharides from natural origin, focusing on the plant-sourced ones, and their innovative potential in skin applications, for instance as woundhealing, antimicrobial, antioxidant and anti-inflammatory, antitu­ moral, and anti-aging agents often called sinks (Heldt & Piechulla, 2021) Starch is the main carbo­ hydrate stored by plants, followed by fructans, and many examples of cell-wall storage polysaccharides All of them are obtained by extrac­ tion, separation, and purification methods, whose differences directly influence the yield, purity, composition, and biological activity dis­ played by the purified polysaccharide (Carpita & Gibeaut, 1993; Delattre et al., 2011) The main methods used to obtain plant-sourced polysaccharides are reviewed below and categorized by subtopics 2.1 Extraction methods We start by considering the hydrophilic property of the large polar molecules of polysaccharides and the fact that they cannot be extracted with organic reagents Therefore, water is the most common solvent and the base solvent for extraction methods, including acid and alkali extraction, and the enzymolysis method (Liu et al., 2020; Ren, Bai, Zhang, Cai, & Del Rio Flores, 2019) The polysaccharide yield obtained from the hot water method can be optimized by using factorial plans, in which different experimental parameters are varied, such as extraction temperature, extraction time, and material-liquid ratio (Liu et al., 2020) Several advantages of this method have been pointed out, including low cost, simple and safe operation, no pollution of reagents, few interfer­ ence substances, and improved polysaccharide solubility (Huang & Huang, 2020); the disadvantages include high consumption of energy, higher cost, low yield, and long operation time (Kakar et al., 2021) The use of acidic solutions with temperature, time, and pHcontrolled conditions is essential to destroy the plant cell wall, thus releasing plant polysaccharides The main advantage of the acid extraction method is the high extraction rate, while the disadvantage is associated with modifications in the polysaccharide structure due to the acidity, high temperatures, and long extraction times (Huang & Huang, 2020) The alkaline extraction method is similar to the above-mentioned method using acid; both of them can destroy the plant cell wall, thus extracting the polysaccharides The main advantages are high yield and short extraction time The main disadvantage is similar to the one of the acid extraction method: when high alkali concentrations are used, the hydrolysis of the polysaccharide can destroy its structure Other disad­ vantages have been mentioned, such as the presence of impurities and residues, the high viscosity of the material obtained (which compro­ mises filtration steps during the process), and its flavor (that potentially affects the quality and color of the polysaccharide) (Huang & Huang, 2020) Enzymolysis is an extraction method where enzyme specificity is used to hasten up the breakdown of the structure of the plant cell wall or the cell membrane, exposing the active components and promoting the dissolution of active substances Given this, enzymolysis is reported to be gentler and more efficient than the other solvent extraction methods (Liu et al., 2020) The advantages are listed as improved extraction ef­ ficiency, shorter extraction time, mild reaction conditions, simplicity, and reduced use of chemical reagents The disadvantages are related to the price of the enzymes, and the limiting factors (enzyme mass con­ centration, temperature, pH) associated with large-scale application (Huang & Huang, 2020) We also highlight ultrasonic extraction (UE) as a conventional method used to maintain the inherent properties of polysaccharides Based on ultrasonic wave cavitation, this method breaks cell walls and accelerates the dissolution of organics in cells, thus improving the yield of polysaccharides It is possible to combine UE with the hot water extraction or the enzymolysis method; both combinations can improve the rate of extraction when the simple methods not produce sufficient yields UE has the advantages of high extraction efficiency, short time, and low energy consumption, while the main disadvantage is the diffi­ culty to reach the best frequency, solid-liquid ratio, and temperature conditions (Liu et al., 2020; Ren et al., 2019) Some other extraction methods have occasionally been introduced and applied in scientific research For instance, high voltage pulsed Extraction, separation, and purification methods used to obtain plant polysaccharides Polysaccharides are purified from plants (seeds and exudates), algae, animals, fungi, and bacteria (Albuquerque, Coelho, Teixeira, & Carneiro-da-Cunha, 2017); however, the production of polysaccharides by bacterial fermentation appears to be an important alternative to those sourced from animals, plants, and seaweed Some advantages of the bacterial polysaccharides have been pointed out, including the easy production method without any constraint of seasons, and extraction and purification without the use of drastic conditions of temperature and chemical reactions (Delattre et al., 2011) Given this information, one could ask why plant polysaccharides continue to be painstakingly explored? This intriguing question can be answered when we consider the medicinal value of plants, their still underexplored biodiversity, and their huge contribution to the contin­ uation of human civilization In higher plants, photosynthesis in the leaves provides carbohydrates for the various heterotrophic plant tissues (e.g., roots, seeds, and other storage organs), as well as to young growing leaves that are not yet able to support themselves by their own photo­ synthesis Leaves that export carbohydrates are often called sources, and young leaves, roots, and storage organs that import carbohydrates are P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 electric field, ultrahigh pressure, microwave, liquid phase pulse discharge, and subcritical water extraction methods have been consid­ ered (Huang & Huang, 2020; Liu et al., 2020; Ren et al., 2019) Super­ critical carbon dioxide extraction is an interesting method and should be highlighted because it is currently being praised as a green separation technology The supercritical fluid of carbon dioxide can be safe, nontoxic, not easy to burn, and leaves no solvent residue, in addition to presenting strong selectivity, low temperature, and the ability to main­ tain the activity of the components (Huang & Huang, 2020) Even considering the great number of possibilities to extract polysaccharides from plants, many researchers combine two or three methods of extraction, which can greatly improve the efficiency of the extraction without over-expensing the process Fig displays the main methods used from the extraction to the purification of natural polysaccharides, for instance, those derived from plant sources factors, especially the low yield Thus, hydrogen peroxide solutions and microporous resins have become alternative and attractive methods for the removal of pigments In addition, small impurities can be removed by dialysis as long as the processing uses small volumes per run (Ren et al., 2019; Shi et al., 2017) After removal from the cell, a mixture composed of different degrees of polymerized polysaccharides is obtained; therefore, deep purification is the basis for studying the relationship between structure and biolog­ ical activity Purification techniques can be categorized as physical separation, chemical precipitation, and chromatographic purification We start by considering physical separation, which can be achieved by membrane separation and ultracentrifugation; the first one uses mem­ branes from varied sources and pore sizes, for instance, microfiltration, nanofiltration, ultrafiltration, and reverse osmosis membranes, while the ultracentrifugation method is based on different deposition ratios (Liu et al., 2020; Ren et al., 2019) Chemical precipitation follows physical separation and is performed with organic reagents and salt solutions It is important to highlight that fractional precipitation is suitable for polysaccharides with large dif­ ferences in solubility and molecular weight Ethanol and methanol are the two conventional reagents used in stepwise precipitation; however, methanol is less commonly used due to its toxicity To isolate acidic polysaccharides, salt solutions containing sodium, potassium or qua­ ternary ammonium are commonly used (Liu et al., 2020; Ren et al., 2019) After physical separation and chemical precipitation, column chro­ matography is an efficient technique for the purification of natural components Considering the physicochemical peculiarities of poly­ saccharides, the method performs the separation of the target substances in a gradual manner under the mechanism of stationary and mobile phases According to the principle of the stationary phase filler, column chromatography can be divided into gel filtration chromatography (GPC), ion exchange column chromatography, and affinity column chromatography Nowadays, diethylaminoethyl (DEAE)-cellulose anion exchange column chromatography is commonly used in the first step, followed by affinity column chromatography This combination is sim­ ple and may be effective for the separation of viscous polysaccharides 2.2 Separation and purification methods After extraction, polysaccharides remain with many impurities, such as inorganic salts, oligosaccharides, proteins, and lignin At this point, it is difficult to evaluate the relationship between structure and activity of crude polysaccharides, thus certain measures are required, including the removal of proteins and pigments The removal of proteins in crude polysaccharides is commonly assessed by Sevag, trichloroacetic acid, and enzymatic methods The first two methods require the denaturation of proteins and centrifugation to remove the maximum content of de­ natured molecules Some repetitions are commonly required to reach good purity, and this is the main disadvantage of both methods Thus, to improve the impurity removal process, enzymatic methods can be combined with the other methods (Huang & Huang, 2020; Liu et al., 2020; Ren et al., 2019) Pigments can oxidize polysaccharides, thus affecting the chromato­ graphic analysis and compromising an accurate identification of the polymer; in view of this, the removal of pigments is an essential step during the separation process Decolorization by the use of activated carbon is the conventional method for the industry; despite its suitability for the large-scale of industrial production, it is restricted by many Fig Experimental flow summary from extraction to purification of plant polysaccharides Combined techniques have been employed to improve purification and achieve good yields These steps (and others, for example high voltage pulsed electric field extraction, liquid phase pulse discharge extraction, microwave extraction, subcritical water extraction, supercritical carbon dioxide extraction, and ultrahigh pressure extraction) are essential for further analyses of the purified polysaccharide P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 with a tendency towards aggregation (Liu et al., 2020; Ren et al., 2019) Generally, it is difficult to obtain pure polysaccharides by performing only one method, thus combined techniques have been employed to improve purification and achieve good yields Further analyses are performed for molecular characterization, evaluation of biological activities, and application of modern techniques for future perspectives The molecular weights of polysaccharides, for example, are usually determined by high-performance liquid chroma­ tography (HPLC) equipped with size-exclusion chromatography (SEC) and refractive index detector/evaporative light scattering detector as well as a UV detector (De Gauquier, Vanommeslaeghe, Heyden, & Mangelings, 2021; Zhang et al., 2021) Considering our goal to sum­ marize the main methods used from the extraction to the purification of natural polysaccharides, we mentioned the steps prior to the charac­ terization Table summarizes different formulations of polysaccharides used on the skin, their sources and the methodologies used for extraction and purification (in combination or not) The following topics of this review focus on each mentioned formulation and other isolated poly­ saccharides added, describing their sources and purification process whenever possible, in addition to their wound-healing, antimicrobial, antioxidant and anti-inflammatory, antitumoral, and anti-aging activities polysaccharide extracted from Hammada scoparia leaves Again, the authors reinforced the edible and biodegradable films with PVA, sub­ mitted them to extensive characterization, and evaluated their woundhealing capability The results demonstrated that the reinforced films exhibited a higher wound-healing potential confirmed by high antioxi­ dant activities in vitro and by histological examination (Eleroui et al., 2021) A great number of works reporting plant-sourced polysaccharides as wound-healing agents have been developed using hydrogel scaffolds because of their excellent biocompatibility, high moisture resistance, and the ability to activate immune cells (Xiang, Shen, & Hong, 2020) When compared with dry wound dressings, hydrogels were considered more comfortable and able to provide a moister healing environment, thereby facilitating wound healing especially in the later stages of the process (Gao, Li, Huang, Zhao, & Wu, 2020) For example, a hydrogel based on the polysaccharide extracted from the orchid Bletilla striata was fabricated for the treatment of acute wounds performed by full-thickness excision in mice Firstly, the poly­ saccharide was extracted with water, precipitated with alcohol, and then tested for cell migration and proliferation using the mouse fibroblast cell line The results showed that the hydrogel significantly accelerated the wound-healing process in vivo in models of skin defect wounds (Zhang et al., 2019) Hydrogels based on low-methoxyl amidated citrus pectin (LMA) or flaxseed gum (FSG) were used for the entrapment of bioactive tripeptide glycyl-L-histidyl-L-lysine and amino acid α-L-arginine FSG was obtained from whole flaxseed (Linus usitatissimum L.) by water extraction, while LMA was commercially obtained The hydrogels were evaluated on experimental cutting wounds affected by extensive skin damage and presented different release behavior kinetics The results demonstrated that animals treated with both hydrogels containing the tripeptide presented significantly higher healing degree and lower healing time than the non-treated group, and the mixture of the tripeptide and α-Larginine in the hydrogels was quite effective in wound healing The histological analysis demonstrated that complete healing was achieved only when using the tripeptide in FSG hydrogel (Synytsya et al., 2020) Another efficient wound-healing composite hydrogel was developed by EL Hosary et al (2020) The polysaccharide derived from Egyptian Avena sativa L (oat) grains was extracted with boiling distilled water, precipitated with absolute alcohol, and then used in formulations with polyethylene glycol 6000 (PEG), polyvinylpyrrolidone K30 (PVP), car­ bopol 940 (Carbopol), hydroxyethylcellulose (HEC), hydroxypropyl methylcellulose (HPMC), and sodium carboxymethylcellulose (NaCMC) to form hydrogels by the freezing-thawing method In vivo evaluation of the anti-inflammatory and the wound-healing activity of the formula­ tions was performed on male rats and compared with a conventional product (Mebo® ointment) The formulation containing the poly­ saccharide and HEC (referred to as hydrogel F7) presented higher antiinflammatory activity and significantly improved wound healing when compared with Mebo®; specifically, F7 presented a wound size reduc­ tion percentage of 99% after 10 days, while the value for Mebo® was 95.4% and the non-treated rats (negative control group) reduced the wound by only 25.5% Sousa et al (2019) studied the in vivo potential of frutalin for wound healing in combination with the galactomannan purified from Cae­ salpinia pulcherrima (popularly known as flamboyant-mirim) seeds using hydrogel and membrane scaffold formulations The hydrogel was applied daily and the latter, carrying 10-fold more frutalin than the daily hydrogel, was implanted at surgery Both formulations were then eval­ uated for dermal wound healing in mice bearing punch biopsy excisional wounds and allowed near-full recovery of wounded skin in 11 days Superabsorbent hydrogels obtained from blends of polysaccharides or simple polysaccharides are the most recent formulation being studied as polysaccharide scaffolds; they are envisioned as promising keys for assisting skin wound healing and regeneration, particularly the emerging role of hydrogels as the next generation skin substitutes for the Applications in skin treatments 3.1 Wound healing Wound healing is a complex biochemical and cellular process con­ sisting of four sequential and orchestrated phases of hemostasis, inflammation, proliferation, and tissue remodeling Repair is necessary when a physical tissue disruption occurs and its success depends on the degree of injury, tissue regeneration ability, necrotic tissue, and foreign body infection (Ribeiro et al., 2020) The reactions in the sophisticated healing process are synergic and ordered, contributing to a wound repair without interruption as shown in Fig Many strategies have been developed in recent decades to attain skin lesion closure, including antibacterial ointments, synthetic growth fac­ tors, polyurethane, polymeric hydrogels, and fiber dressings Consid­ ering such options, many factors must be observed for choosing a wound dressing, including the stage of the current wound, the frequency of dressing replacement, the cost of the treatment, and association with drugs Either synthetic or naturally-sourced polymeric materials are used for the development of dressings (foams, hydrogels, hydrocolloids, films, membranes), which present various advantages suitable for the treatment of specific types of wounds However, some dressings are unable to initiate cellular responses, thus it is necessary to combine the dressing with other molecules that can stimulate and trigger target cell responses at the beginning of healing (Mayet et al., 2014) Biopolymers that can interact with innate cells and promote wound repair have an advantage over the existing synthetic dressings, appearing as an important alternative for the current wound care field Polysaccharides are the major class of biomolecules with ideal physicochemical, mechanical, and biological properties for wound dressings; besides the above-mentioned properties of these macromol­ ecules, they can be molded into different scaffolds that are crucial to developing functional biomaterials (Sahana & Rekha, 2019) For example, edible and biodegradable films based on the polysaccharide extracted from Trigonella foenum-graecum, known as fenugreek, rein­ forced by poly(vinyl alcohol) (PVA), were prepared, characterized, and evaluated in vivo through wound healing on CO2 laser fractional burns in rats The good biocompatibility demonstrated by the reinforced films stimulated the surrounding healthy cells at the wound site by generating the growth factors required for wound healing, thus improving reepithelialization and accelerating wound closure in treated animals (Feki et al., 2019) More recently, a similar study was developed by using the P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 Table Summary of skin actions of polysaccharides extracted from plants, including their extraction and purification methods and polysaccharidic preparation Action Extraction and purification methods Polysaccharidic preparation References Wound healing FSG obtained by water extraction, and commercially obtained low-methoxyl amidated citrus pectin Polysaccharide obtained by ethanolic extraction (75% ethanol) Polysaccharide obtained by hot water extraction and absolute ethanol precipitation Other components commercially obtained Water extraction and ethanol precipitation Hydrogels based on LMA or FSG Synytsya et al., 2020 Composite hydrogel based on the polysaccharide fraction from PAP and carboxymethyl cellulose Egyptian Avena sativa L polysaccharide associated with PEG, PVP, Carbopol, HEC, HPMC, and NaCMC to form hydrogels Guar gum hydrogels cross-linked with borax and loaded with silver nanoparticles Film based on the polysaccharide extracted from leaves of Hammada scoparia reinforced with PVA Film based on the polysaccharide extracted from Trigonella foenum-graecum reinforced with PVA Hydrogel based on the polysaccharide extracted from the orchid Bletilla striata Hydrogel and membrane scaffold formulations based on the galactomannan purified from Caesalpinia pulcherrima Oral administration of the Sanguisorba officinalis L polysaccharide Glycyrrhiza soluble polysaccharide Polysaccharide from the seeds of Pimpinella anisum P anisum seed polysaccharide Wang et al., 2020 Not mentioned Not mentioned Water extraction followed by alcohol precipitation Not mentioned Hot water and ethanol extraction followed by ethanol precipitation Water extraction followed by alcohol precipitation Water extraction followed by alcohol precipitation Hot water extraction followed by ethanol precipitation with water redissolution Not mentioned Not mentioned Antimicrobial activity Hot water extraction followed by isopropanol precipitation Hot water extraction Hot water extraction and ethanol precipitation Not mentioned Not mentioned Not mentioned Antioxidant and antiinflammatory actions Hot water extraction and ethanol precipitation Not mentioned Hot water extraction followed by ethanol precipitation with water redissolution Not mentioned Not mentioned Anticancer effect Not mentioned Not mentioned Not mentioned Not mentioned Anti-aging effects Hot water extraction Water extraction Ethanol precipitation (95% ethanol) Hot water extraction Not mentioned Not mentioned Water extraction Not mentioned Not mentioned Not mentioned El Hosary et al., 2020 Talodthaisong et al., 2020 Feki et al., 2019 Eleroui et al., 2021 Zhang et al., 2019 Sousa et al., 2019 Zhang, Chen, & Cen, 2018 Hao et al., 2020 Ghlissi et al., 2020 Ghlissi et al., 2020 Linum usitatissimum L., water-soluble polysaccharide Polysaccharides from the inner bark of Grewia mollis and from the leaves of Hoheria populnea Daucus carota polysaccharides Trabelsi et al (2020) Pearman et al., 2019 Crataegus azarolus L var aronia polysaccharides Annona muricata leaf polysaccharide Membrane of the xyloglucan extracted from the seeds of tamarind (Tamarindus indica) Water soluble polysaccharide extracted from the evergreen shrub Salicornia arabica Water-soluble neutral polysaccharides isolated from bamboo (Phyllostachys pubescens) leaves Polysaccharide from fenugreek (Trigonella foenumgraecum) seeds Water-soluble polysaccharide extracted from sorghum (Sorghum bicolor L.) seeds P anisum seed polysaccharide Rjeibi, Zaabi, & Jouida, 2020 Byun, Song, & Kim, 2020 Campolo et al., 2020 Gum of the polysaccharide extracted from Elaeagnus angustifolia L Polysaccharide-rich extract of stem barks from Caesalpinia ferrea Polysaccharide from goji berry (Lycium barbarum) Polysaccharide from L barbarum Ethanol soluble polysaccharide extracted from flower buds of Sophora japonica L Polysaccharide extracted from Bael (Aegle marmelos L.) pulp Panax ginseng acidic polysaccharides Scaphium scaphigerum polysaccharide gel Agave sisalana leaf polysaccharide formulated as nano-emulsion Polysaccharides from P ginseng Topical application of the polysaccharide fraction isolated from L barbarum Starch in an emulsion containing titanium dioxide and zinc oxide Hydrogel based on the polysaccharide extracted from Basella alba Polysaccharide from mesquite (Prosopis juliflora) fruits Polysaccharide-rich preparation from Anadenanthera colubrine Polysaccharide from Rosa chinensis Ghazala et al., 2015 Hammami et al., 2018 Xiao et al., 2020 Ktari et al., 2017 Slima et al., 2019 Ghlissi et al., 2020 Wang et al., 2021 Pereira et al., 2016 Cezar et al., 2019 Li et al., 2017 Li et al., 2019 Pynam & Dharmesh, 2019 Kim et al., 2019 Kanlayavattanakul, Fungpaisalpong, Pumcharoen, & Lourith, 2017 Barreto et al., 2017 Kim et al., 2019 Neves et al., 2020 Marto et al., 2016 Lourith & Kanlayavattanakul, 2017 Damasceno et al., 2020 Katekawa et al., 2020 Pressi et al., 2019 Flaxseed gum (FSG); low-methoxyl amidated citrus pectin (LMA); Periplaneta americana (PAP); polyethylene glycol 6000 (PEG); polyvinylpyrrolidone K30 (PVP); carbopol 940 (Carbopol); hydroxyethylcellulose (HEC); hydroxypropyl methylcellulose (HPMC), and sodium carboxymethylcellulose (NaCMC) P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 Fig Wound healing represented as a dynamic interactive process, from injury to repair, and synthetic or natural-sourced polymeric materials used for the development of dressings treatment of chronic wounds (Capanema, Mansur, Jesus, et al., 2018; Qureshi, Nishat, Jadoun, & Ansari, 2020; Shanmugapriya & Kang, 2019) Injectable hydrogels are also novel healing tools that, when injected into the wound, form a gel in situ able to fill the wound in three dimensions, thus reaching deep and irregular wounds that traditional hydrogels cannot fill (Gao et al., 2020) A recent study reported guar gum hydrogels, cross-linked with borax and loaded with silver nanoparticles, which are injectable, exhibit rapid self-healing, and show antibacterial properties towards both Grampositive and Gram-negative bacteria, thus confirming novel and prom­ ising expectations about injectable hydrogels (Talodthaisong et al., 2020) The oral administration of a purified polysaccharide was also eval­ uated in an animal burn wound model SOP (Sanguisorba officinalis L polysaccharide) was extracted from the roots of the plant (commonly known as great burnet) by hot water and ethanol extraction, in addition to ethanol precipitation, and administrated at 50 and 200 mg/kg in normal male Wistar mice In this experiment, ten animals were included in a normal control group, i.e., with no burn application Macroscopic results demonstrated a significant wound contraction and reduced epithelialization time in the treated groups when compared to the nontreated animals, while the histopathological examination of the treated mice showed collagen deposition and a thick and well-developed epidermal layer covering the entire area of the burn wound, which was similar to the adjacent skin of the normal control group The authors suggested that the enhancement of burn wound healing by SOP resulted from promotion of collagen synthesis and angiogenesis during skin wound repair (Zhang et al., 2018) Glycyrrhiza uralensis, also known as Chinese licorice, is a flowering plant native to Asia; the effects of a Glycyrrhiza soluble polysaccharide (GP) combined with microcapsule collagen on the repair of a rat injury model were discussed at different levels by Hao et al (2020) GP was extracted with hot water and precipitated with ethanol to a final con­ centration of 80% (v/v); the precipitates were obtained and dissolved with distilled water, and then deproteinized by the Sevag method Four treatments were considered in this work: wounds treated with sterile collagen sponge (model group), sterile gauze (negative group), collagen sponge loading with 12.5 μg ferulic acid microcapsule (ferulic acid group), and collagen sponge loading with 72 μg GP in a microcapsule formulation (polysaccharide-microcapsule group) The most important histopathological result was associated with the granulation tissue of the polysaccharide-microcapsule group, whose hyperplasia of blood vessels and fibroblasts revealed that GP could improve tissue regeneration, i.e., the content of hydroxyproline in granulation tissue increased, the proliferation of capillaries and fibroblasts was activated, and the number of microvessels in the wound increased, thus achieving effective and faster wound healing when compared to the model and negative groups A polysaccharide, called PAP, was isolated from the seeds of Pimpi­ nella anisum, popularly known as anise, using a water extraction meth­ odology followed by alcoholic precipitation with water redissolution PAP was isolated, characterized as a polysaccharide containing galac­ tose, glucose, and mannose, and applied to evaluate the laser burn wound-healing and anti-inflammatory activities in mice A beneficial wound-healing effect was revealed by the topical application of the PAP hydrogel on the burn lesions; the authors reported accelerated wound contraction, in addition to re-epithelization and remodeling phases after seven days of treatment (Ghlissi et al., 2020) The seeds of Linum usitatissimum L., popularly known as linseed or flax, were used to extract a water-soluble polysaccharide (LWSP) by Trabelsi et al (2020) The application of LWSP on CO2 laser fractional burn wounds produced in rats was efficient to significantly increase the percentage of burn contraction (98.6%) after days of injury According to the histological assessment, the authors demonstrated that the LWSPtreated group had a higher content of hydroxyproline than the other groups, thus confirming the effective remodeling phase on the tested group Another type of experimental study was developed with Malvaceae derived polysaccharides Pearman et al (2019) isolated polysaccharides from the inner bark of Grewia mollis and from the leaves of Hoheria populnea (commonly known as New Zealand mallow, lacebark or hou­ here) and evaluated their wound-healing properties by using 3T3 fibroblast cells cultured in supplemented DMEM Results indicated that both polysaccharides have positive effects on the mechanisms involved in fibroplasia, with the one derived from G mollis being the better treatment for faster wound closure Despite major recent advances in the wound-treatment field, the search for the ideal dressing continues with ongoing development There is a growing concern about the healing sector, which is the development of prevention therapies rather than treatments An exciting time for polysaccharide wound materials is ahead through the expansion of manufacturing processes such as 3D printing, electrospinning, and combination 3D printing-electrospinning, with the potential to create patient-specific wound dressings with design freedom using computer­ ized models (Aduba & Yang, 2017) Innovation is expected to continue strongly in advanced wound care in the coming years P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 3.2 Antimicrobial properties to prevent skin infections showed that Gram-positive bacteria were more sensitive to both poly­ saccharides than Gram-negative ones, corroborating previous studies (Hammami et al., 2018; Rjeibi et al., 2020) The mechanisms involved in the antibacterial activity of these polysaccharides are still not clear However, He, Yang, Yang, and Yu (2010) suggested that the poly­ saccharides could induce the disruption of the cell wall of bacteria and increase ion permeability Antimicrobial potential of CAP and CAS could be related with their higher total sugar contents (Rjeibi et al., 2020) Bamboo (Phyllostachys pubescens) leaves feature an abundant composition of carbohydrates but are seldom attacked by microorgan­ isms, indicating that constituents in bamboo leaves could be an anti­ microbial agent In this context, polysaccharides from bamboo leaves have been interesting candidates to explore antimicrobial activities Water-soluble neutral polysaccharides (NPs) were isolated from bamboo (P pubescens) leaves and their antibacterial activities were tested NPs showed inhibitory activity on the growth of E coli, S aureus and B subtilis at concentrations of 0.50–50.0 mg/mL, suggesting that poly­ saccharides could perform a protective role against bacteria in bamboo leaves (Xiao et al., 2020) Thus, many polysaccharides extracted from plants have demonstrated potential as natural antimicrobial against microbes associated with skin infections Skin infections involve microbial growth and invasion within the skin or wound in the skin These infections induce the activation of the immune system, causing inflammation and tissue damage (Quaresma, 2019) Plant polysaccharides have been explored as antimicrobial agents against microbes associated with skin infections, thereby assist­ ing in prevention and healing processes Clinically relevant microbe strains have been isolated from human skin infections Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Enterobacteriaceae, an­ aerobes, β-hemolytic streptococci and enterococci are examples of bacte­ ria isolates in skin infections, and Candida spp., Aspergillus spp and Fusarium spp as fungal isolates (Berger et al., 2019; Di Domenico et al., 2017) Xyloglucan is a hemicellulose extracted from seeds of the tamarind tree (Tamarindus indica) It consists of a heterogeneous collection of polysaccharides found in the cell walls of gymnosperms and angio­ sperms, and their amounts vary significantly in different species (Kul­ karni et al., 2017) It is composed of a β-(1,4)-ᴅ-glucan backbone with substitutions of half to three-fourths of the glusosyl residues by α-linked xylosyl residues at the 6-position These substitutions can vary in ac­ cording to taxonomic group (Fu, Liu, & Wu, 2019; Wang, Xu, Ding, & Kong, 2018) In addition, xyloglucan possesses a “mucin-like” molecular structure that provides mucoadhesive properties, generating interest as a protective barrier (Piqu´ e, G´ omez-Guill´en, & Montero, 2018) A study used a formulation containing xyloglucan and pea protein to evaluate its in vitro effects on the membrane permeability of human HaCaT kerati­ nocytes infected by S aureus This bacterium is found on the skin and mucous membranes and is responsible for many cases of skin infection in humans The pretreatment with xyloglucan and pea protein significantly improved trans-epithelial electrical resistance, a marker of skin barrier function, and reduced bacterial adherence, preventing S aureus infec­ tion (Campolo et al., 2020) There is great interest in aggregating more value to the carrot (Daucus carota) peel by-product, which is usually discarded by the carrot processing industry, considering that carrot by-products still have high contents of bioactive compounds Despite this context, little attention has been devoted to carrot peel polysaccharides Antibacterial activity of water-soluble polysaccharides obtained from carrot peels (D carota) through hot water extraction followed by isopropanol precipitation was investigated High antibacterial activity was observed through the growth inhibition of E coli, Salmonella enterica, Enterobacter sp., S aureus and Micrococcus luteus, in culture media containing the water-soluble polysaccharides from carrot peels (200 mg/mL), suggesting its poten­ tial for microbial infection prevention (Ghazala et al., 2015) Antimicrobial properties of a water-soluble polysaccharide extracted from an evergreen shrub, Salicornia arabica, were investigated against bacteria, yeast and fungal strains in vitro It showed antimicrobial ac­ tivity against E coli, S aureus, Listeria ivanovii, B subtilis, Candida albi­ cans, Fusarium phyllophilum and F oxysporum, being more pronounced against Gram-positive bacteria than Gram-negative ones Previous studies with other plant polysaccharides have revealed similar results, which could be related to the presence of an external phospholipid membrane in Gram-negative bacteria, limiting the diffusion of hydro­ phobic compounds through its lipopopysaccharide cover, and acting as a barrier against hyperacidification The monosaccharide composition could also influence antimicrobial activity These findings suggest an effective antibacterial and antifungal agent and may contribute to pre­ vent skin-related infections (Hammami et al., 2018) Polysaccharides extracted from pulp (CAP) and seeds (CAS) of azarole (Crataegus azarolus L var aronia) by hot water exhibited effec­ tive antimicrobial properties against the following pathogenic bacteria: E coli, Enterococcus faecalis, P aeruginosa, Listeria monocytogenes, Kleb­ siella pneumoniae, Bacillus cereus, S aureus and Salmonella typhimurium (Rjeibi et al., 2020) The results of antibacterial activity evaluated by inhibition zone diameter and minimum inhibitory concentration 3.3 Antioxidant, anti-inflammatory and anticancer actions Oxidative stress of the skin occurs mainly due to reactive oxygen species (ROS) interacting with cutaneous targets, such as proteins, DNA, lipids and organelles, damaging them and causing cellular senescence (Gu, Han, Jiang, & Zhang, 2020) Some possible harmful effects on the skin caused by its oxidative stress include an acceleration of the aging process, enhanced production of oxidized lipids that increases the excretion of sebaceous glands, disruption of the skin barrier, degrada­ tion of the extracellular matrix, alteration of melanocyte activity and induction of skin roughness and inflammation (Costa & Santos, 2017) ROS can originate from enzymatic and non-enzymatic systems, for example, the mitochondrial electron transport chain, NADPH oxidases, xanthine oxidoreductase, peroxisomal oxidases, cytochrome P450, lip­ oxygenases, UV irradiation, chromophores, xenobiotics and iron ions Several antioxidant defense systems exist in the skin, which are more concentrated in the epidermis than in the dermis; these antioxidant molecules include glutathione, SPRR2 (small proline rich repeat) pro­ teins, superoxide dismutase (SOD), catalase, coenzyme Q, ferritin, vitamin C and E (Rinnerthaler, Bischof, Streubel, Trost, & Richter, 2015) Cell injury occurs when there is an imbalance in the oxidant/ antioxidant systems (Pisoschi & Pop, 2015) However, it has been re­ ported that some polysaccharides have antioxidant action (Albuquerque et al., 2020) and, therefore, these macromolecules from plants can contribute to the defense against skin oxidative stress Ktari et al (2017) extracted a polysaccharide from fenugreek (T foenum-graecum) seeds, called FWEP, using hot water followed by ethanol precipitation and resuspension in water Antioxidant activity of FWEP, at concentrations of 1–10 mg/mL, was determined using different in vitro assays, such as scavenging capacity of 1,1-diphenyl-2picrylhydrazyl (DPPH) radical, ferric reducing power, chelating activ­ ity of ferrous ion and inhibiting β-carotene bleaching The authors formulated a hydrogel with FWEP to treat skin wounds in Wistar rats and take advantage of its antioxidant action since the property to fight free radicals accelerates and improve wound healing Thus, FWEP hydrogel (15 mg/L) also showed antioxidant activity in vivo by decreasing lipid peroxidation, oxidation protein products and H2O2 levels in skin tissues on the 14th day after wound excision (Ktari et al., 2017) A water-soluble polysaccharide of glucose, called SWSP, was extracted from sorghum (Sorghum bicolor L.) seeds and its antioxidant action was determined by in vitro analyses including ferrous chelating activity, reducing power converting iron (Fe+3) in ferric chloride to the ferrous form (Fe+2) and DNA nicking Then, SWSP hydrogel was applied P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 to treat second-degree laser burn wound in Wistar rats, whose woundhealing efficiency has been reported to be due to its antioxidant ac­ tion In addition, histological analyses of biopsies from the burn area showed an anti-inflammatory effect of SWSP since less inflammatory cells were observed compared to control groups (treated with physio­ logical serum and glycerol), which showed active inflammatory lesion accompanied by infiltration of inflammatory cells (Slima et al., 2019) Annona muricata (commonly known as soursop or graviola) leaf polysaccharide (ALP) was obtained through boiling water extraction with subsequent alcoholic precipitation ALP at a concentration of 50 μg/mL reduced the apoptosis of normal human epidermal keratinocytes exposed to gamma irradiation, increased the intracellular activity of the antioxidant enzymes SOD and catalase and decreased the levels proinflammatory cytokine IL-1β and indicators of inflammasome signaling pathways Moreover, in an in vivo approach, the radiationinjured skin of mice was treated with a cream containing 0.2% ALP (w/v), which was applied topically to the irradiated skin lesion This treatment increased the levels of SOD and catalase whose measurements were performed in skin tissue homogenates, in addition to reducing the epidermal thickness and the number of apoptotic cells in the tissue area that was irradiated (Byun et al., 2020) The polysaccharide isolated from the seeds of P anisum reported in Section 3.1 Wound healing, also revealed anti-inflammatory activity; PAP had its antioxidant action characterized in vitro by DPPH scav­ enging and reducing power assays with PAP at concentrations of 0.2–1 μg/mL and 10–50 μg/mL, respectively In addition, there was appre­ ciable anti-inflammatory action of PAP by reducing the volume of carrageenan-induced paw edema in adult Swiss mice and discrete signs of inflammatory cells in their histological images Combined with these findings, in the homogenate of edema tissue a reduction in the levels of malondialdehyde, a pro-oxidant molecule, and increase in SOD activity were reported, thus indicating an improvement in tissue oxidative stress caused by carrageenan (Ghlissi et al., 2020) Polysaccharides obtained from the gum of Elaeagnus angustifolia L (EAP), which is commonly recognized as oleaster or Russian olive, showed anti-inflammatory action since EAP (125 and 250 μg/mL) pro­ moted a decrease in nitric oxide levels, which contributed to the path­ ogenesis of inflammation, and inhibited inflammatory pro-cytokines (TNF-α, IL-1β and IL-6) in human primary epidermal keratinocytes stimulated by lipopolysaccharide Using a mouse model of dry skin pruritus with inflammation induced by acetone/ether, it was found that topical treatment with EAP (10 mg/d for days) increased the epidermal layer thickness and reduced both the infiltration of inflam­ matory cells and the levels of inflammatory mediators, such as IL-6, TNF-α, IL-17 and cyclooxygenase-2, in the skin tissue region (Wang et al., 2021) In addition to the isolated polysaccharide, formulations containing these carbohydrates could be used to assist in the antiinflammatory action on skin Thus, polysaccharide-rich extracts of ´, stem barks from Caesalpinia ferrea, popularly called pau-ferro or juca promoted a reduction of leukocyte infiltration in cutaneous wounds of Wistar rats as well as modulated the expression of inflammatory medi­ ators in skin biopsy homogenates (Pereira et al., 2016) Accumulation of oxidizing agents as well as the persistence of a chronic inflammatory state can also mediate carcinogenesis (Vaidya, Chhipa, Sagar, & Pathak, 2020) Skin cancer is a heterogeneous group of cancers that comprise cutaneous melanoma and non-melanoma Their incidence is increasing worldwide, with sun exposure being a relevant etiologic factor in skin cancer development (Zegarska et al., 2017) Despite the advances in modern therapies for skin cancer management, interest in natural compounds has increased in the search for a safer and more effective strategy of prevention Studies have focused on plant polysaccharides mediating blocking effects against skin damage related to carcinogenesis (Fig 3), and this property has showed a relationship with their antioxidative, anti-inflammatory, anti-proliferative and antiangiogenic activities (Li et al., 2017; Li et al., 2019) Exposure to UV radiation can activate oncogenes and inactivate tumor suppressor genes, altering survival and proliferation of kerati­ nocytes (Pacini et al., 2017) Skin cancer mediated by UV radiation in­ volves diverse pathways related to proliferation, DNA damage, mutations, apoptosis, metabolism, reactive oxidative species (ROS) production, immune response and inflammation (Fig 3) (Li et al., 2017; Li et al., 2019) A polysaccharide from goji berry (Lycium barbarum) has exhibited antioxidative and anti-inflammatory effects on multiple tis­ sues and its photoprotective effect against ultraviolet B (UVB)-induced damage was evaluated in immortalized human keratinocytes (HaCaT cells) Skin damage induced by UVB affects the lipid membrane, proteins and DNA through UVB absorption by target molecules in skin cells, in addition to over-generation of ROS that oxidize lipids, proteins and DNA (Cezar et al., 2019) The L barbarum polysaccharide showed partial protection potential against UVB irradiation-induced photo-damage by activation of the Nrf2/ARE pathway, resulting in ROS scavenging and reduction in DNA damage, and also suppressed the UVB-induced p38 MAP pathway, that plays a vital role in UVB-induced skin cancer (Li et al., 2017) An ethanol soluble polysaccharide extracted from flower buds of the Japanese pagoda tree (Sophora japonica L.) was evaluated concerning its potential to attenuate UVB-induced damage in HaCaT cells irradiated with UVB rays The pretreatment with its polysaccharide significantly reduced cytotoxicity and ROS generation, increased cell viability, and down-regulated the expression of phosphor-JNK and phosphor-p38 MAPK proteins via the MAPK pathway, which is related to apoptotic cell death (Li et al., 2019) Skin damage induced by UV irradiation can result in overexpression of galectin-3, triggering dysregulation of tyrosinase, metastasis and inflammation which have been related to aggressive skin cancer (Wang et al., 2020) In this context, a xylorhamnoarabinogalactan I pectic polysaccharide extracted from Bael (Aegle marmelos L.) pulp, called BAPP1, showed significant inhibition of expression of galectin-3, the immunoregulatory cytokines IL10/IL17, inflammation and tyrosinase In addition, BAPP1 improved gut microbiota status in experimental animals and enhanced apoptosis, being an alternative for skin cancer protection (Pynam & Dharmesh, 2019) Anti-oxidative and anti-inflammatory properties of Panax quinque­ folium (American ginseng) polysaccharides, called GPS, are of interest to investigate for their potential protective effects against UVB-induced skin damage Topical formulations containing GPS nanoparticles were developed to evaluate the therapeutic effect to inhibit UVB-induced skin cancer UVB irradiation was conducted with a dose of 300 mJ/cm on SKH1 hairless mice and topical formulations were applied before and after UVB induction Skin and blood samples were collected to measure inflammatory cytokine production A significant reduction in all cyto­ kine production was registered in pre-treated mice skin and blood samples Skin histology analysis of pre-treated mice also revealed a protective effect against epidermal damage and proliferation, suggesting that the topical formulation containing GPS nanoparticles was a prom­ ising alternative to prevent skin cancer (Akhter, Mumin, Lui, & Char­ pentier, 2021) Drug delivery systems based on polysaccharides have been devel­ oped as vehicles in skin cancer therapy due to high stability, controlled drug release, non-toxicity, biodegradability and bioavailability Carboxymethylcellulose (CMC) is a derivative of cellulose poly­ saccharide used in the development of nanocarriers for anticancer drug delivery CMC-based prodrug hydrogels composed of CMC with the anticancer drug doxorubicin (Carvalho et al., 2018) and doxorubicin hydrochloride (Capanema, Mansur, Carvalho, et al., 2018) were devel­ oped for topical chemotherapy of melanoma skin cancer Both hydrogels showed activity for killing melanoma cancer cells with less cytotoxicity to normal cells in vitro, being a potential strategy for skin cancer treatment P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 Fig Representation of UV irradiation-induced skin damage that may trigger skin carcinogenesis and polysaccharides acting for skin protection 3.4 Anti-aging effects protected against collagen degradation and against increase in epidermis thickness (hyperkeratosis), a common damage in skin chronically exposed to UV radiation However, they did not reduce the levels of UV-induced MMPs (MMP-1, MMP-2 and MMP-9) (Neves et al., 2020) Although some polysaccharides may not have the property of skin photoprotection, they can be used in formulations that help to improve the photoprotective action of some compounds Thus, a Pickering emulsion was prepared containing titanium dioxide, zinc oxide, and starch particles (without photoprotective activity) with green coffee oil, which has a high sun protection factor It was found that the starch increased the photoprotective action of the oil by a synergistic action through an in vitro assay spreading the formulations on a substrate tape followed by exposure to UVB and UVA radiations (Marto et al., 2016) One of the fundamental characteristics of moisturizers is the power of hydration by reducing the loss of water from the skin surface, called transepidermal water loss, which consequently can reduce the appear­ ance of wrinkles (Draelos, 2018) Thus, the skin moisturizing property of some plant carbohydrates has been attributed to their ability to reduce transepidermal water loss as shown in Fig A gel containing the polysaccharide obtained by maceration in water of the malva nut (Scaphium scaphigerum) promoted moisture retention for up to 70 on the skin of human volunteers, evaluated by a Corneometer® This formulation had better action than the gels containing commercialized polysaccharides (Kanlayavattanakul et al., 2017) A polysaccharide extract obtained by maceration in water of the white orchid flowers (Dendrobium cv Khao Sanan) also conferred greater skin hydration in healthy volunteers for 150 They were monitored through skin capacitance determined by the amount of electrical energy which can be accumulated by the skin due to the higher water dielectric constant; skin hydration and capacitance are directly proportional (Kanlayavattana­ kul, Pawakongbun, & Lourith, 2019) An extract from aerial parts of Ceylon or Malabar spinach (Basella alba), with a high polysaccharide content, was obtained from a 3-h extraction in distilled water under heating at 50 ◦ C and formed a hydrogel in water Thus, the hydrating power of B alba preparation was Skin is a natural physical barrier for the body; however, its deterio­ ration together with changes in the permeability of the epidermis can lead to cutaneous aging This process is caused by the exposure of in­ dividuals to risk factors found in the environment, such as solar radia­ tion, cigarette smoke and pollution, as well as the way the body responds through genetic and non-genetic mechanisms to these stressors (Krut­ mann, Bouloc, Sore, Bernard, & Passeron, 2017) Intrinsic factors, for example, hormones, shortening and dysfunction of telomeres, also contribute to the skin aging process, which can be expressed through reduced elasticity, appearance of wrinkles, dryness, changes in the thickness of epidermis, dermal-epidermal junction and dermis (Wang & Dreesen, 2018) In this context, some biomolecules from plants have been used in cosmetic formulations that fight skin aging as an alternative to synthetic chemical compounds that can be harmful to health and/or the environment (Ahmed, Mikail, Zamakshshari, & Abdullah, 2020) Acidic polysaccharides were produced from red ginseng (Panax ginseng) by-product through hot water extraction and had their antiphotoaging effect demonstrated by inhibition of the matrix metalloproteinase-1 (MMP-1) expression in a cell line of human epidermal keratinocytes (HaCat) These cells received a pretreatment with the acidic carbohydrates for h and then were exposed to chronic solar UV at 25 kJ/m2 It was found that the treatment with these mac­ romolecules (mainly at the concentration of 20 μg/mL) reduced the levels of MMP-1 and its mRNA as well as of the AP-1 transcription factor that up-regulates MMP-1 expression (Kim et al., 2019) It is known that MMP-1 expression is increased in the skin after UV irradiation and this enzyme has collagenolytic action contributing to skin damage and aging ´pez-Otín, 2017) Some poly­ (Freitas-Rodríguez, Folgueras, & Lo saccharides with anti-photoaging action not act through this UVinduced MMP inhibition route For example, the polysaccharide frac­ tion isolated from Lycium barbarum fruit was used to topically treat the hairless skin of mice that were exposed to UV radiation using an in­ candescent lamp of 300 W Both treatments with this polysaccharide fraction and its combination with photobiomodulation therapy P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 proven using a Corneometer® and applying these samples at different concentrations (0.05–0.10% w/v) on the skin of human volunteers The extract, besides not causing irritation to the skin, allowed better hy­ dration compared to treatments with the vehicle and negative control, that is, water and untreated skin, respectively The hydrating capacity of the polysaccharide in this material has been attributed to the hydro­ philic groups of this macromolecule capable of absorbing water (Lourith & Kanlayavattanakul, 2017) A polysaccharide from mesquite (Prosopis juliflora) fruits was char­ acterized as α-glucan, a glucose polysaccharide containing α-1,6-glyco­ sidic bonds In the purification process, the fraction of the extract solubilized in water containing the polysaccharide was subjected to gel chromatography A formulation containing 3.0% of the extract with this carbohydrate was obtained through the wet granulation process and was applied to the skin of volunteers This formulation retained a higher water content in the stratum corneum compared to the controls that did not receive treatment and those treated with a commercial product called Aloe vera gel; the analysis was made 1–5 h after application Moreover, the formulation reduced transepidermal water loss compared to the vehicle by a clinical analysis after 30 days of use (Damasceno et al., 2020) Nanotechnology can also be applied to deliver these preparations with anti-aging properties Thus, a nanoemulsion was developed containing 5% of a fraction of polysaccharides obtained from a by-product of the leaves of Agave sisalana, commonly known as sisal (whose extraction proceeded with the addition of 95% ethanol to the crude extract) The nanoformulation increased the water content of the stratum corneum compared to the vehicle (nanoemulsion without fraction), from to h after a single topical application on the skin of volunteers (Barreto et al., 2017) An extract obtained from the in vitro cell culture of Chinese rose (Rosa chinensis) had a high polysaccharide content and was character­ ized by having moisturizing and anti-aging actions attributed to increasing the expression of aquaporin-3, a water-carrying trans­ membrane protein, in the reconstructed human epidermis in comparison with untreated samples (Pressi et al., 2019) Another polysacchariderich preparation from Anadenanthera colubrine, popularly known as angico, and its moisturizing power was investigated in ex vivo skin fragments obtained from surgery The human tissues treated with the preparation (3% w/v) showed a higher expression of aquaporin-3, filaggrin and involucrin (the latter two proteins are important for corneocyte cohesion) compared to fragments of the placebo group (treated with Carbopol Gel) and the negative control that did not receive treatment In addition, a clinical evaluation in human volunteers showed a reduction in transepidermal water loss by the extract (Kate­ kawa et al., 2020) 3.5 Plant polysaccharides spotlight for skincare Cosmetic products are complex mixtures of chemical compounds from synthetic and natural sources, with different physico-chemical and functional properties, to obtain products with high quality that are safe for human health Nowadays, there is an emerging tendency of cosmetic industries to develop natural biodegradable products that are compat­ ible with biological tissues, which are preferred for incorporation into cosmetic products, especially skincare products (Ahmad, 2021) Considering plant components with biological properties attractive for skincare, essential oils, phenols, pigments and polysaccharides can be highlighted (Gao, Kuok, Jin, & Wang, 2019; Vaughn, Clark, Sivamani, & Shi, 2018) A wide range of plant polysaccharides such as cellulose, starch, pectin and mucopolysaccharides are present in commercial cosmetic compositions due to their ability to function as hydrogels, emulsifiers, film formers and moisturizers, promoting skin protection and treatment (Singh et al., 2021) Cellulose is a structural polysaccharide derived from plant cell walls, with many hydroxyl groups and a high water-absorption capacity, allowing the formation of hydrogels stabilized by chemical bonds, ¨ken et al., 2020) In hydrogen bonding or ionic interactions (Palanto addition, cellulose properties such as emulsifier, film former, humectant and anti-caking agent are interesting to improve the quality and efficacy of topical formulations, and therefore cellulose is often incorporated into moisturizing cosmetics such as lotions, creams and masks for skincare (Seddiqi et al., 2021) Some cosmetic ingredients based on cellulose are commercially available, for example, SENSOCEL® cellulose fibers, from CFF GmbH & Co KG (Arnstaedter, Germany), and NAT­ PURE® CELLGUM PLUS from Sensient Cosmetic Technologies (South Plainfield, United States) Starches from natural sources such as corn, rice and tapioca are often added to skincare cosmetic formulations to improve their functional­ ities Starch's properties of water and oil absorption and adsorption are important to absorb moisture and perspiration; to allow deep cleaning Fig Representation of a polysaccharide skin treatment with moisturizing capacity for preventing transepidermal water loss in relation to skin without treatment 10 P.B.S Albuquerque et al Carbohydrate Polymers 277 (2022) 118824 and exfoliation; and sebum control In addition, starch can help to reduce unwanted body odor, and improve the feel and texture of the skin (Daudt, Back, Cardozo, Marczak, & Külkamp-Guerreiro, 2015) Pectin is a complex polysaccharide found in the cell wall of plants commercially extracted mainly from citrus fruits and apple pomace (Picot-Allain, Ramasawmy, & Emmambux, 2020) It is commonly used in cosmetic formulations for skincare, since it helps to keep an emulsion from separating into its oil and liquid components, besides increasing the thickness of the aqueous portions of cosmetics and acting as gelling agent (Lupi et al., 2015) Pectin also exhibits various reactive chemical groups in its structure, being a good stabilizer and viscosity control in formulations of creams, lotions, gels, moisturizers and other skincare products (Valle et al., 2020) A naturally occurring fructose polysaccharide, inulin, found in the roots and rhizomes of several plants, is a prebiotic ingredient in skincare formulations Prebiotic activity of inulin reduces the growth of preju­ dicial bacteria in favor of friendly microorganisms naturally present on the skin, and helps preserve its healthy appearance In addition, inulin is also a humectant agent that helps keep the skin hydrated (NiziołŁukaszewska, Bujak, Wasilewski, & Szmuc, 2019) Mucopolysaccharides found in medicinal plants have been reported to promote skin treatment and protection Wound-healing activity of Aloe vera gel has been attributed to mucopolysaccharides, which stim­ ulate fibroblasts to produce more collagen, promoting the remodeling of the wound (Gao et al., 2019) Eriodictyon 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plant polysaccharides can be a limiting factor for large-scale commercial use in the cosmetic industry Moreover, investigations of the shelf life of possible formula­ tions based on these polysaccharides are encouraged, as are in­ vestigations of their biocompatibility with different skin types to highlight possible adverse effects Thus, it is expected that in the future, after adequate testing in vivo and even in human volunteers, these car­ bohydrates can be used in formulations applicable to the skin for clinical use with therapeutic, preventive and even aesthetic purposes Acknowledgements ´gico The Conselho Nacional de Desenvolvimento Científico e Tecnolo (CNPq) is recognized for fellowships (MTSC and LCBBC) and grants The ˜o de authors are also thankful for financial support from the Fundaỗa ` Ciˆ Amparo a encia e Tecnologia Estado de Pernambuco (FACEPE) and the Coordenaỗ ao de Aperfeiỗoamento de Pessoal de Nível Superior (CAPES) The authors also thank The British Council for 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Trabelsi et al (2020) Pearman et al., 2019 Crataegus azarolus L var aronia polysaccharides Annona muricata leaf polysaccharide Membrane of the xyloglucan extracted from the seeds of tamarind (Tamarindus... constant; skin hydration and capacitance are directly proportional (Kanlayavattana­ kul, Pawakongbun, & Lourith, 2019) An extract from aerial parts of Ceylon or Malabar spinach (Basella alba),... polysaccharides Scaphium scaphigerum polysaccharide gel Agave sisalana leaf polysaccharide formulated as nano-emulsion Polysaccharides from P ginseng Topical application of the polysaccharide fraction

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