Skincare application of medicinal plant polysaccharides — A review

Carbohydrate Polymers 277 (2022) 118824

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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.

1. 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: (L.C.B.B. Coelho).
/>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 ( />

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 do 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

2. 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
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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. 1 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. 1. 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.
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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 1 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

3. 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. 2.
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
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Carbohydrate Polymers 277 (2022) 118824

Table 1
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).

5


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Carbohydrate Polymers 277 (2022) 118824

Fig. 2. 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 8 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.

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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
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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 5 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.

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Carbohydrate Polymers 277 (2022) 118824

Fig. 3. 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. 4. A gel containing the
polysaccharide obtained by maceration in water of the malva nut
(Scaphium scaphigerum) promoted moisture retention for up to 70 min 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 min. 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 1 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 do 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
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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 2 to 5 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,
ăken 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. 4. Representation of a polysaccharide skin treatment with moisturizing capacity for preventing transepidermal water loss in relation to skin without treatment.
10


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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 californicum, a medicinal plant
to treat skin wounds also known as yerba santa, is a source of moistur­
izing ingredients such as mucopolysaccharides and glycoproteins that
act via hydrogen bonding of water by their sugar moieties (Juliano &
Magrini, 2018).

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4. Conclusions
Knowledge about extraction, characterization, and biological func­
tions of plant polysaccharides has increased during the last years. Many
polysaccharides derived from plants were obtained by hot water
extraction and alcohol precipitation; their skincare actions could also be
performed by applying these macromolecules in different formulations,
for instance, foams, hydrogels, dressings, and nanotools showing effi­
cient results when applied to the skin. It is possible to consider plant

polysaccharides as promising sources for the natural prevention and
management of skin damage, infections, and cancer thanks to their
healing, antimicrobial, and protective properties. Despite having these
interesting applications, the purification yield of 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
` Ci
Amparo a
encia e Tecnologia do Estado de Pernambuco (FACEPE) and
the Coordenaỗ
ao de Aperfeiỗoamento de Pessoal de Nớvel Superior
(CAPES). The authors also thank The British Council for support
enabling international collaboration.

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