ArticlePDF Available

Anti‐Wrinkle Therapy: Significant New Findings in the Non‐Invasive Cosmetic Treatment of Skin Wrinkles with Beta‐Glucan

Authors:
  • Results Driven Agriculture Research

Abstract and Figures

Oat beta-glucan is a water soluble, linear polymer of glucose consisting of 1,4 (70%) and 1,3 (30%) linkages with an average molecular weight of 1 × 106 Da. Scientific reports indicate beta-glucan is a film-forming moisturizer, a biological response modifier, and a promoter of wound healing. Our objective was to study the penetration of oat (1,4:1,3) beta-glucan in human skin models and to evaluate clinically its efficacy for reducing fine-lines and wrinkles. Penetration studies performed on human abdominal skin used a single application of 0.5% beta-glucan solution at a dose of 5 mg per cm2. The results showed that beta-glucan, despite its large molecular size, deeply penetrated the skin into the epidermis and dermis. A clinical study of 27 subjects was performed to evaluate the effects of beta-glucan on facial fine-lines and wrinkles. After 8 weeks of treatment, digital image analysis of silicone replicas indicated a significant reduction of wrinkle depth and height, and overall roughness. This work is the first ex vivo and in vivo demonstration of the physiological effects of beta-glucan in the penetration and restructuring of human tissue. The study supports the use of oat beta-glucan in the care and maintenance of healthy skin and the cosmetic treatment of the signs of aging.
Content may be subject to copyright.
Reprint
VOLUME 8, NUMBER 1 JANUARY / MARCH 2005
magazine
The Global Publication of the International Federation of Societies of Cosmetic Chemists
R. Pillai, M. Redmond, J. Röding
Anti-Wrinkle Therapy: Significant New Findings in the
Non-Invasive Cosmetic Treatment of Skin Wrinkles with
Beta-Glucan
2
IFSCC Magazine – Reprint
INTRODUCTION
Oat has a long history of safe use to pro-
vide fast, temporary relief of the itching,
redness, and pain associated with many
minor skin irritations such as poison ivy/
oak/sumac, insect bites, and allergy [1]. In
the cosmetic application of beta-glucan,
consumers have described various bene-
fits including excellent, sustained mois-
turization properties together with an im-
proved, smoother appearance of the skin.
In recent years new wound product appli-
cations for beta-glucan have been found
in the management of partial thickness
burns, shallow abrasions, and laser treat-
ment [2, 3]. It has been reported that topi-
cal glucan administration enhances
wound healing by increasing macrophage
infiltration into the wound milieu, stimulat-
ing tissue granulation, collagen deposi-
tion, and re-epithelialization, together
with increasing the tensile strength of the
recovered wound [4, 5].
Laboratory experiments using beta-glu-
can from cereal (1,4; 1,3 linear glucose
polymer) and fungi (1,3; 1,6 branched glu-
cose polymer) indicated that all beta-glu-
cans are biological response modifiers,
with oat beta-glucan producing the great-
est cytokine induction activity in macro-
phages [6, 7].
The mechanism by which glucan or glu-
can-induced immunomodulators enhance
wound repair has remained elusive. We
do know that beta-glucan receptors exist
on mammalian macrophages and fibrob-
lasts [4, 8]; the effect of glucan on wound
repair is speculated to involve macro-
phage release of wound growth factors
with the further direct and indirect modu-
lation of fibroblast activity, including col-
lagen biosynthesis.
In the case of wounds, the disruption of
the dermal barrier gives clear and open
access of macrophages and fibroblasts to
topically applied beta-glucan. It remained
to be determined if cellular effects could
be achieved through normal, intact skin
and if the structure of aged skin could be
affected positively through the cosmetic
application of beta-glucan.
EXPERIMENTAL
Oat (1,4; 1,3) beta-glucan
Beta-glucan is the soluble fiber found in
the cell walls of oat kernels
(Figure 1)
.
Structurally, oat beta-glucan is a linear
polymer of glucose consisting of 1,4 (70%)
and 1,3 (30%) glycosidic linkages
(Figure
2)
.
The beta-glucan used in the present stud-
ies was extracted from oat and supplied
as a clear, viscous, 1% solution (Symrise
Inc., New Jersey). Briefly, the extraction
method comprised the aqueous, mild al-
kali (pH 9.2) extraction of beta-glucan from
oat bran, followed by the removal of pro-
tein, and ultrafiltration through a 0.1 mi-
Anti-Wrinkle Therapy: Significant New Findings
in the Non-Invasive Cosmetic Treatment of
Skin Wrinkles with Beta-Glucan
Ravi Pillai1, Mark Redmond2, Joachim Röding3
1Symrise Inc., 10 Gordon Drive, Totowa, New Jersey, USA
2Ceapro Inc. 1008 RTF University of Alberta, Edmonton, Alberta, Canada
3Symrise GmbH & Co KG., Bleichenbrücke 10, 20354 Hamburg, Germany
Corresponding author – email: ravi.pillai@symrise.com
Abstract
Oat beta-glucan is a water soluble, linear polymer of glucose consisting of 1,4 (70%) and 1,3 (30%) linkages with an
average molecular weight of 1x106Da. Scientific reports indicate beta-glucan is a film-forming moisturizer, a biolog-
ical response modifier, and a promoter of wound healing. Our objective was to study the penetration of oat (1,4 :1,3)
beta-glucan in human skin models and to evaluate clinically its efficacy for reducing fine-lines and wrinkles.
Penetration studies performed on human abdominal skin used a single application of 0.5% beta-glucan solution at a
dose of 5 mg per cm2. The results showed that beta-glucan, despite its large molecular size, deeply penetrated the
skin into the epidermis and dermis.
A clinical study of 27 subjects was performed to evaluate the effects of beta-glucan on facial fine-lines and wrinkles.
After 8 weeks of treatment, digital image analysis of silicone replicas indicated a significant reduction of wrinkle depth
and height, and overall roughness.
This work is the first
ex vivo
and
in vivo
demonstration of the physiological effects of beta-glucan in the penetration
and restructuring of human tissue. The study supports the use of oat beta-glucan in the care and maintenance of
healthy skin and the cosmetic treatment of the signs of aging.
Keywords: Beta-glucan, skin penetration, wrinkles, anti-aging
3
IFSCC Magazine – Reprint
cron filtration system. The resulting solu-
tion was double precipitated with ethanol
and resuspended to a final concentration
of 1%. The ultrafiltration of the beta-glu-
can solution produced a clear solution
confirmed by a low turbidity (<40 Neph-
elometric Turbidity Units: NTU). The mole-
cular weight range of the beta-glucan was
determined to be 0.5 x 106– 1.0x 106Da as
measured by the method of Wood [9].
Skin penetration study
In the first study we examined the dermal
penetration of (1,4; 1,3) beta-glucan into
sections of surgically-removed, human
abdominal skin. The penetration of beta-
glucan was visualized using Calcofluor
White, a beta-glucan specific fluorescent
stain. The use of Calcofluor White also
allowed semi-quantitative measurement
of beta-glucan penetration with fluores-
cence densitometry [10, 11].
Sections of abdominal tissue were re-
moved surgically without the
subcutaneous fat. The skin was
sliced to fit a penetration and
deposition chamber based
on a Franz Diffusion Cell. The
skin sections were first deep
frozen by liquid nitrogen and
sterilized by gamma-radiation,
which destroyed all yeast and
fungal elements that could in-
terfere with the assay. After ir-
radiation, the skin-section was
thawed and the specimens
were inspected for integrity be-
fore use with a pressure test.
Next, the skin section was con-
ditioned with respect to surface
temperature and moisture con-
tent. This condition was achiev-
ed by pre-heating the liquid
medium in the test chamber and
adjusting the air flow through the cham-
ber’s ventilation channel. A macroscopic
and physical examination of the skin spec-
imen was carried out before the test to
ensure suitability, and the area of the test
application site was 10cm2for all sam-
ples. During testing, the skin specimen
was supplied with a uniformly circulated
nutrient medium, which rinsed its lower
surface. The experimental conditions
were non-occlusive.
The test procedure involved one applica-
tion of 0.5% (w/w) beta-glucan solution
using a micro dose applicator at a dose of
5 mg per cm2of skin. After 8 hours of in-
cubation, the skin tissue was deep frozen.
It was then cut into thin slices and air
dried. Then the skin was cut from lower to
higher possible concentration, meaning
deeper dermis to horny layer.
The specimens were placed on thin glass
slides and allowed to dry. One drop of
Calcofluor White (BactidropTM, Remel,
Lenexa, KS, USA) was added and stained
for 30 seconds. The excess stain was re-
moved by washing with deionized water.
The specimens were then examined using
a fluorescent microscope with an excita-
tion wavelength ranging between 400
500 nm and a peak of 440 nm. Untreated
skin was used as the control.
The tests were done simultaneously with
two samples and one control for each vol-
unteer skin. All tests were repeated with
the skin of five volunteers.
Anti-aging study
In the second study, we performed a clin-
ical evaluation of the capacity of beta-
glucan to alleviate the extrinsic signs of
aging. The study was conducted in Col-
orado during the winter months to provide
a dry environmental challenge together
with a high exposure rate to UV.
The test was conducted on a panel of 27
subjects, with two carbomer gel formula-
tions; one contained 0.1% (w/w) (1,4; 1,3)
beta-glucan and the other was placebo.
The subjects applied the randomly as-
signed products twice daily, using a half-
face design. The subjects observed a
3-day conditioning period immediately
prior to baseline measurements. Each of
the 27 subjects treated their left and right
sides of the face, twice daily for eight
weeks. After 8 weeks of treatment, the
skin was evaluated for changes from
baseline values of various parameters
including fine lines, wrinkles and rough-
ness.
The clinical study included subjective and
objective assessments which were rec-
orded at baseline and 2, 4, and 8 weeks.
For the evaluation of fine-lines and wrin-
kles, silicone replicas of the outer canthus
of the eye area (crow’s feet) were sub-
jected to digital image analysis by expert
graders. Macrophotography was also
Figure 1: Fluorescent stained section of an oat
kernel. The beta-glucan present in the cell wall of
the oat fluoresces a brilliant blue when stained
with Calcofluor White.
Figure 2: Chemical structure of oat beta-glucan showing the beta 1,4 and beta 1,3 glycosidically linked glucose polymer structure.
4
IFSCC Magazine – Reprint
used to evaluate the changes in fine lines
and wrinkles.
RESULTS AND DISCUSSION
The results of the skin penetration study
showed that (1,4; 1,3) beta-glucan had
penetrated the skin into the epidermis and
dermis
(Figures 3 and 5)
. No fluorescence
staining occurred in the control skin sec-
tion which was not treated with beta-glu-
can
(Figure 4)
. Quantitative assay of the
fluorimetric staining indicated that a sig-
nificant portion of the product (28.5% of
the applied beta-glucan) had entered the
skin
(Figure 6)
.
The clinical trial results indicated a higher
incidence of improvement with (1,4; 1,3)
beta-glucan than with the placebo.
Fig-
ure 7
shows the average percentage
change of the selected parameters from
the baseline, compared to the treatment
with placebo. The silicone replicas after
the test period demonstrated a smoothing
of the cutaneous surface after 8 weeks
of treatment with (1,4; 1,3) beta-glucan.
Macrophotography of the left and right
sides of the face also showed a reduction
in lines and wrinkles.
These results represent remarkable new
findings which will contribute to our un-
derstanding of the interaction of skin with
beta-glucan, and the ability of beta-glucan
to penetrate the skin deeply and elicit cel-
lular changes.
In the past, the potential ability of beta-
glucan to penetrate the skin was disre-
garded because it was thought that the
high molecular weight (> 0.5x106Da) of
the compound would prevent it from pen-
etrating into the epidermis and dermis,
and it would therefore be unable to inter-
Figure 3: Photograph of dermis skin sec-
tion treated with 0.05% (w/w) (1,4; 1,3) be-
ta-glucan solution (magnification x125).
Figure 4:Photograph of the control dermis
skin section (magnification x125).
Figure 5: High magnification photograph
of epidermis skin section treated with a
0.05% (w/w) solution of beta-glucan. Note
that beta-glucan staining is associated
with the inter-cellular matrix indicating
that the beta-glucan permeates the skin
by passing between cells rather than
passing through cells directly (magnifica-
tion x250).
stratum corneum epidermis dermis
Percentage of beta-glucan penetrated
Figure 6: Graphical analysis of the fluorimetric data obtained from the
skin penetration study. The blue bars represent the beta-glucan treat-
ed skin and the green bars represent the control skin. The results indi-
cate that beta-glucan is able to penetrate into the lower levels of the
skin, and therefore is able to interact with the fibroblasts and other
structural elements.
deep wrinkle all wrinkle average peak roughness
reduction reduction reduction reduction
Average percentage change from baseline
Figure 7: Graphical analysis of the facial results of the clinical trial obtained
through digital picture analysis after 8 weeks. The blue bars represent the
beta-glucan treated skin and the green bars represent the control skin.
5
IFSCC Magazine – Reprint
act with macrophages and fibroblasts.
Beta-glucan is able to adopt a number of
conformations and is typically extracted
in the form of aggregate particles > 1µm
which are clearly visible under a light
microscope. It is understandable that
such large particles may not be expected
to enter the skin and the effects of beta-
glucan were thought to be limited to the
skin’s surface.
However, the beta-glucan used in the
present penetration study was subject to
sub-micron filtration to produce an aggre-
gate-free, low-turbidity solution with no
particles visible under the light micro-
scope. Examination of the micrographs in
Figure 5
shows that the beta-glucan used
in our study does not enter the skin by
direct passage through the cells of the
epidermis and dermis, but instead works
its way into the skin by passing through the
inter-cellular matrix. Such a process may
be facilitated by a diffusion gradient and
by lipid and phospholipid interactions. In-
teractions of beta-glucan with lipids are
known and are the basis of the health-en-
hancing, lipid-controlling properties rec-
ognized by the FDA [12].
Having penetrated the skin to the dermis,
beta-glucan is able to interact with spe-
cific cells, namely macrophages and
fibroblasts. Results of
in vitro
experiments
have demonstrated that beta-glucan in-
teracts with macrophages to induce the
production of IL-1, which indirectly pro-
motes the production of procollagen by
fibroblasts. In addition, beta-glucan has
been shown to interact with fibroblast re-
ceptors, which results directly in the pro-
duction of procollagen [13, 14]. The con-
version of procollagen to collagen and its
incorporation into collagen bundles would
result in the type of effects noted in our
clinical study, specifically the facial skin
tightening leading to a reduction of fine
lines and wrinkles.
Questionnaires and subject follow-ups
indicated that the effects on fine lines
and wrinkles associated with use of beta-
glucan treatment were long-lived but not
permanent. With normal cellular turnover,
there was an appearance of fine lines. It
may be speculated that the continued use
of products containing beta-glucan would
result in a sustained improvement of ap-
pearance.
The results presented in the present study
offer a cosmetic alternative to other more
invasive treatments aimed at the reduc-
tion of fine lines and wrinkles in an aging
population. Injectable fillers like collagen
either from human, bovine, or porcine
sources are common, and recently
hyaluronic acid fillers have also been
introduced. Such fillers produce tempo-
rary, soft tissue with effects that last on
average for 3 to 4 months. With a similar
duration of effect, the cosmetic use of
Botulinum
toxin type A has been reported
to have increased multifold since 1997
[15]. Actives like retinoic acid and coen-
zyme Q10 are also used for the treatment
of wrinkles [16-18]. The regular and fre-
quent use of cosmetics containing oat (1,4;
1,3) beta-glucan is a new and exciting tool
in the fight against the signs of aging.
CONCLUSION
Oat (1,4; 1,3) beta-glucan is a natural
active ingredient offering significant per-
formance-enhancing properties for per-
sonal care applications. Our studies have
shown that the molecule, despite its con-
siderable molecular weight, is able to en-
ter the stratum corneum and epidermis
and penetrate deep into the dermis. The
observed effects of beta-glucan on tissue
restructuring and wrinkle reduction are
most likely effects mediated by fibroblast
stimulation and collagen deposition in the
dermis. These unique properties make oat
beta-glucan a promising and effective
ingredient for cosmetics.
REFERENCES
[1] United States FDA,
Federal Register
, 68
(2003) 35346-35348.
[2] Lee, S.B., Jeon, H.W., Lee, Y.W., Lee,
Y.M.L., Song, K.W., Park, M.H, Nam, Y.S.,
and Ahn, H.C., Bio-artificial skin com-
posed of gelatin and (1!3), (1!6)-glu-
can,
Biomaterials
, 24 (2003) 2503-2511.
[3] Delatte, S.J., Evans, J., Hebra, A., Adam-
son, W., Othersen, H.B., and Tagge, E.P.,
Effectiveness of beta-glucan collagen for
treatment of partial thickness burns in
children,
J. Pediatr. Surg.
, 36 (2001) 113-
118.
[4] Wei, D., Zhang, L., Williams, D.L., and
Browder, I.W., Glucan stimulates human
dermal fibroblast collagen biosynthesis
Figure 8: Proposed mechanism for the skin penetration of beta-glucan. Above the stra-
tum corneum (horny layer) and epidermis, beta-glucan forms a thin film to promote mois-
turization. Within the dermis, beta-glucan is able to produce collagen synthesis through
direct interaction with fibroblasts and through indirect, cytokine mediated, interaction
with macrophages. Collagen synthesis is one possible mechanism by which the elas-
ticity of the skin is enhanced.
through a nuclear factor-1 dependent
mechanism,
Wound Repair and Regen-
eration
, 10 (2002) 161-168.
[5] Portera, C.A., Love, E.J., Memore, L.,
Zhang, L., Mueller, A., Browder, W., and
Williams, D.L., Effect of macrophage
stimulation on collagen biosynthesis in
the healing wound,
Am. Surg.
, 63 (1997)
125-131.
[6] Yun, C.H., Estrada, A., Van Kessel, A.,
Gadjadhar, A.A., Redmond, M., and Laar-
veld, B., Beta (1-3, 1-4) oat glucan en-
hances the resistance to
Eimeria vermi-
formis
in immunosuppressed mice,
Int. J.
Parasitol.
, 27 (1997) 329-337.
[7] Estrada, E., Yun, C.H., Van Kessel, A., Li,
B., Hauta, S., and Laarveld, B., Immuno-
modulatory activities of oat beta-glucan
in-vitro
and
in-vivo
,
Microbial. Immunol.
,
41 (1997) 991-998.
[8] Wei, D., Williams, D.L., and Browder, I.W.,
Activation of AP-1 and SP1 correlates
with wound growth factor gene expres-
sion in glucan-treated human fibroblasts,
International Immunopharmacology
, 2
(2002) 1163-1172.
[9] Wood, P.J., Weisz, J., and Mahn, W., Mol-
ecular characterization of cereal beta-
glucans, II. Size-exclusion chromatogra-
phy for comparison of molecular weight,
Cereal Chem.
, 68 (1991) 530-536.
[10] Wood, P.J. and Fulcher, R.G., Interaction
of some dyes with cereal beta-D-glucans,
Cereal Chem.
, 55 (1978) 952-966.
[11] Szmacinski, H. and Lakowicz, J.R., Sodi-
um green as a potential probe for intra-
cellular sodium imaging based on fluo-
rescence lifetime,
Anal. Biochem.
, 250
(1997) 131-138.
[12] United States FDA,
Federal Register
, 63
(1998) 8103-8121.
[13] Mueller, A., Raptis, J., Rice, P.J., Kalb-
fleisch, J.H., Stout, R.D., Ensley, H.E.,
Browder, W., and William, D.L., The in-
fluence of glucan polymer structure and
solution conformation on binding to
(1!3)-beta-D-glucan receptors in a hu-
man monocyte-like cell line,
Glycobiol.
,
10 (2000) 339-346.
[14] Wei, D., Zhang, L., Williams, D.L., and
Browder, I.W., Glucan stimulates human
dermal fibroblast collagen biosynthesis
through a nuclear factor-1 dependent
mechanism,
Wound Repair Regen.
, 10
(2002) 161-168.
[15] The Economist, Pots of Promise,
The
Economist
(2003) May 22, 2003 Edition.
[16] Rosenthal, D.S., Roop, D.R., Huff, C.A.,
Weiss, J.S., Ellis, C.N., Hamilton, T., Voor-
hees, J.J. and Yuspa, S.H., Changes in
photo-aged human skin following topical
application of all-trans retinoic acid,
J.
Invest. Dermatol.
, 95 (1990) 510-515.
[17] Personelle, J., De Campos, S., Ruiz, Rde
O., and Ribeiro, G.Q., Injection of all-trans
retinoic acid for treatment of thin wrin-
kles,
Aesthetic Plast Surg.
, 21 (1997) 196-
204.
[18] Hoppe, U., Bergemann, J., Diembeck, W.,
Ennen, J., Gohla, S., Harris, I., Jacob, J.,
Kielholz, J., Mei, W., Pollet, D., Schacht-
schabel, D., Sauermann, G., Schreiner, V.,
Stab, F., and Steckel, F., Coenzyme Q10,
a cutaneous antioxidant and energizer,
Biofactors
, 9(1999) 371-8.
!
IFSCC Magazine – Reprint
6
... These modifications can considerably improve BG solubility and increase the potential use of these molecules as a bioactive ingredient Yuan et al., 2019). In this case, certain properties demonstrated by functionalized BG, such as antioxidant Theis et al., 2019), antibacterial (Wan-Mohtar et al., 2016), wound healing (Yasuda et al., 2018), ultraviolet radiation (UV) protection (Zülli et al., 1998) and antiaging (Pillai et al., 2005), can be promptly used for skincare applications. ...
... As discussed in a review by Majtan and Jesenak (2018), BG has a direct influence on keratinocytes, fibroblasts, and macrophages, leading to enhanced reepithelialization by stimulating cellular proliferation and migration through dectin-1 receptors. Additionally, the interaction between BG and fibroblasts stimulates collagen production, facilitating the restoration of the extracellular matrix and promoting wound closure and tissue repair (Pillai et al., 2005). ...
... Furthermore, they promote the generation of ROS and trigger inflammation processes (Zhang & Duan, 2018). To reduce the impact of these factors, the antioxidant and immunomodulatory capacity of BG, paired with its anti-aging properties such as UV protection (Zülli et al., 1998) or wrinkle reduction (Pillai et al., 2005), demonstrate the potential of this molecule for anti-aging purposes. A representation of how BG interrelate with our skin is explained in Fig. 3. ...
... β-Glucans are known to enter the stratum corneum and epidermis, penetrating deep into the dermis [108,109]. They do not enter the cell directly but penetrate the skin through the intercellular space [108]. ...
... β-Glucans are known to enter the stratum corneum and epidermis, penetrating deep into the dermis [108,109]. They do not enter the cell directly but penetrate the skin through the intercellular space [108]. β-Glucans can occur in many conformations and are typically extracted in the form of aggregate particles > 1 μm which can be visible under a light microscope. ...
... Such large particles may not enter the skin and the effects of β-glucans were thought to be limited to the skin's surface. In an in vitro penetration study, oat glucans consisting of β-(1→3, 1→4) linkages in a backbone were subjected to submicron filtration to produce an aggregate-free, low-turbidity solution without particles visible under a light microscope [108]. It was shown that purified β-glucans penetrate the skin through the intercellular space [108]. ...
Article
Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet. These valuable organisms are more than food, they fit in perfectly as a novel market group known as nutra-mycoceuticals. Immune-balancing mushroom dietary fibers and secondary metabolites such as polyphenols are the main focus of the healthcare industry. Wellness and cosmetic companies are increasingly using mushroom extracts rich in these ingredients. This review considers the basic molecular immunomodulatory mechanisms of action of the most commonly used mushroom dietary fibers, β-glucans. The literature data on their bioavailability, metabolic transformations, preclinical and human clinical research, and safety are discussed. Immunomodulatory mechanisms of polyphenol ingredients are also considered. These molecules present great potential in the design of the new immunity balancer formulations according to their widespread structural diversity. Finally, we draw attention to the perspectives of modern trends in mushroom nutraceutical and cosmeceutical formulations to strengthen and balance immunity.
... Several products containing β-glucans, as well as their purified form, have already been commercialized. The obtaining sources of these commercial β-glucans include oats (Pillai et al. 2005;Sharafbafi et al. 2014), barley (Barone Lumaga et al. 2012Brennan et al. 2013), yeasts (Kittisuban et al. 2014;Samuelsen et al. 2014), rice (Villanueva et al. 2019), algae and bacteria (Belcarz et al. 2013;Ningtyas et al. 2019), and fungi (Park et al. 2001;Suzuki et al. 2005;Brennan et al. 2013). In addition to the products already available on the market, and due to the β-glucans potential, several products are developed in different fields, such as medicine, pharmaceuticals, food, cosmetics, chemical industries, veterinary medicine, and animal food industries (Zhu et al. 2016). ...
Article
Full-text available
Among the most important sources of β-glucans are edible and medicinal mushrooms. These molecules are components of the cellular wall of basidiomycete fungi (mushrooms) and can be extracted even from the basidiocarp as the mycelium and its cultivation extracts or biomasses. Mushroom β-glucans are recognized by their potential effects as immunostimulants and immunosuppressants. They are highlighted as anticholesterolemic, anti-inflammatory, adjuvant in diabetes mellitus, mycotherapy for cancer treatment, as well as adjuvants for COVID-19 vaccines. Due to their relevance, several techniques of β-glucans extraction, purification, and analysis have already been described. Despite the previous knowledge of β-glucans’ benefits for human nutrition and health, the main information about this topic refers to the molecular identification, properties, and benefits, as well as their synthesis and action on cells. Studies on biotechnology industry applications (product development) and the registered products of β-glucans from mushrooms are still limited and more common for feed and healthcare. In this context, this paper reviews the biotechnological production of food products containing β-glucans from basidiomycete fungi, focusing on food enrichment, and presents a new perspective on fungi β-glucans’ use as potential immunotherapy agents. Key points • Mushrooms’ β-glucans for product development in the biotechnology industry • Biotechnological production of food products containing mushrooms’ β-glucans • Basidiomycete fungi β-glucans are used as potential immunotherapy agents Graphical Abstract
... Collagen production is associated with the reduction of fine lines and wrinkles, improving the elasticity of facial skin. There is also evidence of the ability of β-glucans to penetrate the skin deeply and promote cellular changes (Pillai et al., 2005). The current data suggest that β-glucans can induce epithelialization, angiogenesis, fibroblast maturation, collagen, and ECM deposition as well as enhance surveillance for DNA-damaged skin. ...
Article
Full-text available
Background: Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules. Purpose: In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging. Methods: Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords. Results: Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions. Conclusion: Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.
... Doğal kaynaklı kozmesötik hammaddeler arasında Pentaclethra macroloba (Pracaxi) meyvesinden elde edilen tohum yağı, hindistan cevizi, jojoba ve argan gibi emoliyan bitkisel yağlar, Ektoin gibi halofilik mikroorganizmalardan elde edilen kozmesötik aktifler, Myrothamnus flabellifolia'dan elde edilen glikoin, yulaftan elde edilen beta glukan örnek verilebilir [21,[30][31][32]. ...
Article
Amaç: Son yıllarda, sentetik hammaddeler ile üretilen kozmetiklerin insan sağlığı ve çevre için oluşturduğu olumsuz etkiler, günümüz tüketicilerinin çevre bilinci doğrultusunda sürdürülebilir ürünleri tercih etmesi ve üreticilerin kurumsal sorumluluk anlayışına verdiği önem ile yeşil kozmetiklere ilgi artmaktadır. Yeşil kozmetik ürünler doğal veya organik hammaddeler ile sürdürülebilir üretim metotları kullanılarak üretilen, geri dönüşümlü veya yeniden kullanılabilir ambalaj ile piyasaya sunulan ürünlerdir. Henüz hiçbir yönetmelikte bu ürün yelpazesi için yaptırım bulunmamaktadır. Ancak Amerika’da USDA/NOP ve Avrupa’da COSMOS, Ecocert, NaTrue, BDIH gibr standartlar ile ISO 16128 gibi harmonize standartlar aracılığıyla hammadde seçimi, üretim aşamaları ve ambalajlama, doğa ve insan sağlığı açısından ürünler kontrol altına alınmaya çalışılmaktadır. Türkiye İlaç Tıbbi Cihaz Kurumu-TİTCK tarafından yayınlanan doğal ve organik kozmetiklere yönelik yönetmelik eki uyarınca ülkemizde doğal ve organik kozmetiklerde ürün iddialarına yönelik sertifikasyon sağlanmalı ve sertifika logosu ambalajda yer almalıdır. Türkiye’de COSMOS sertfikaları ETKO ve IFC Global gibi sertifika sağlayıcıları aracılığı ile alınabilmektedir. Sonuç ve Tartışma: Bu derlemede, doğal ve organik ürün standartlarının oluşum süreci ve şartları, yeşil formülasyonlar ve hammadde değişimleri, üretimde kullanılan yeşil kimya prensipleri ve sürdürülebilirlik açısından yeşil kozmetikler ele alınmıştır.
... The physical properties of the drug product arising from the combination of the hydrogel base and proprietary b-glucan active ingredient may also contribute to the improved skin quality outcomes observed. [18][19][20][21] There were no meaningful differences in elastosis observed at Day 104 between the groups; however, meaningful differences in wrinkling persisted at Day 104 from Day 28, which were not statistically significant. Post hoc statistical power analysis suggests that statistical significance at Day 104 in wrinkling could be achieved with double the subject numbers, and the positive longer-term results on wrinkling from the use of the TR-987 gel could be investigated further. ...
Article
Full-text available
Background: After laser resurfacing, it is imperative that an appropriate postoperative regimen is followed for optimal wound healing. There is currently no consensus about which agents should be used. Objective: To evaluate the safety and efficacy of a novel macrophage-activating gel in a Phase 2B trial to be used after fractionated ablative laser resurfacing of the chest. Materials and methods: Forty-two adults who received fractionated CO2 laser resurfacing of the chest were randomized (active or placebo) for 5 consecutive days after procedure. Skin quality at baseline and follow-up was assessed by a blinded evaluator using the Fitzpatrick-Goldman Wrinkle Scale. Subject satisfaction with skin healing and quality was also assessed. Results: At 28 days according to the Fitzpatrick-Goldman Wrinkle Scale, 85% of subjects achieved an improvement of at least 33% for the active group versus 50% in the placebo group (absolute difference 35%; p = .04). Similarly, 75% of subjects achieved an improvement score of at least 33% in elastosis in the active group versus 35% in the placebo group at 28 days (40% absolute difference; p = .011). Conclusion: This study confirms the potent effects of the novel macrophage-activating gel for optimization of skin healing and quality after laser resurfacing of the chest.
... The physicochemical, functional, and technological properties of β-glucan are extremely different, depending on the source of origin [1]. This polysaccharide is used in the therapeutic, cosmetic, fitness, and professional sports fields [2,3]. Interest in β-glucan has arisen because it is a powerful immunostimulant, prebiotic, and dietary fiber [4,5]. ...
Article
Full-text available
The article systematizes information about the sources of β-glucan, its technological functions and practical aspects of its use in dairy and milk-based products. According to the analysis of scientific information, the main characteristics of β-glucan classifications were considered: the source of origin, chemical structure, and methods of obtention. It has been established that the most popular in the food technology of dairy products are β-glucans from oat and barley cereal, which exhibit pronounced technological functions in the composition of dairy products (gel formation, high moisture-binding capacity, increased yield of finished products, formation of texture, and original sensory indicators). The expediency of using β-glucan from yeast and mushrooms as a source of biologically active substances that ensure the functional orientation of the finished product has been revealed. For the first time, information on the use of β-glucan of various origins in the most common groups of dairy and milk-based products has been systematized. The analytical review has scientific and practical significance for scientists and specialists in the field of food production, in particular dairy products of increased nutritional value.
Article
β-glucan is a well-known functional and bioactive food ingredient. Recently, some studies highlighted several interesting pharmacological activities, such as hypocholesterolemic, hypoglycemic, immunomodulatory, antitumor, antioxidant and anti-inflammatory. The aim of this study is to evaluate a novel application of β-glucan obtained from barley for the development of formulations for skin use. Several water suspensions were obtained from barley flour of different particle sizes treated by high power ultrasonic (HPU) technique. Barley flour fraction in the range of 400 - 500 μm allowed to obtain a stable suspension, represented both by a water soluble and water insoluble fraction of β-glucans, that showed excellent film forming ability. The plasticizer sorbitol as well as the bioadhesive biopolymer acacia gum were added to this suspension in order to obtain a gel suitable to prepare films by casting. The obtained films demonstrated suitable mechanical properties and ability to stimulate in vitro keratinocytes growth suggesting its possible application in dermatological field as for wound treatment. This study demonstrated the dual use of barley suspension: as excipient and as active ingredient.
Article
Full-text available
The influence of food and nutrition on health and immunity for both human and animals are being demonstrated. Phytochemicals are natural compounds present in cereals, beans, fruits, vegetable, and other plants, believed to enhance immune response for both human and animals. One of these phytochemicals is β-Glucans that are heterogeneous polysaccharides consisted of branched long chains of D-Glucose units present in cereals such as barley, wheat, and oats, and also present in microbial cell walls for yeasts, fungi, bacteria, and algae. β-Glucans extracted from cereals and mushroom were investigated for their positive impact on immunomodulation for both human and animal health. These β-Glucans proved to enhance immune system for innate response as the first defense against microbial infection, toxins, and self-tumor cells, and also, enhance adaptive immune that also referred to specific immunity as the second defense in response to antigen-specific lymphocytes against microbial infection, toxins, and self-tumor cells.
Article
Full-text available
Los productos naturales juegan un papel relevante como fuente de ingredientes biológicamente activos con importancia cosmética y dermatológica. En los últimos años, los cosméticos basados en productos naturales han ganado una gran cantidad de atención no solo por parte de los investigadores sino también del público debido a la creencia general de que son mejores a los sintéticos, además de ser inofensivos, lo cual no necesariamente podría ser cierto, por lo que en este artículo se aborda la ciencia detrás de la formulación en los denominados cosméticos naturales, así como una descripción general de los ingredientes activos naturales que se pueden encontrar en ellos. Profundizamos en algunas pruebas: in vitro, in silico y ex vivo, utilizadas para analizar su efectividad como fotoprotectores solares, antienvejecimiento, anti-hiperpigmentación y toxicidad, así mismo se aborda la controversia que genera el uso de pruebas in vivo.
Article
Full-text available
Previous studies have shown that beta-glucans extracted from yeast or fungi potentiate immune responses. In the present study, the immunomodulatory activities of beta-(1-->3,1-->4)-glucan, derived from oats, were investigated. The ability of oat beta-glucan (ObetaG) to stimulate IL-1 and TNF-alpha release from murine peritoneal macrophages and the murine macrophage cell line P338D1, was assessed. In vitro stimulation of macrophages with ObetaG resulted in the production of IL-1 in a dose and time-dependent manner, whereas only small amounts of TNF-alpha could be detected in the culture supernatants. ObetaG also induced the production of IL-2, IFN-gamma and IL-4 secretion in a dose-dependent manner in cultured spleen cells. The intraperitoneal administration of ObetaG in mice resulted in the accumulation of leucocytes, predominantly macrophages, in the peritoneal cavity. Furthermore, ObetaG was tested for its ability to enhance non-specific resistance to a bacterial challenge in mice. Survival of mice challenged with Staphylococcus aureus was enhanced by a single intraperitoneal administration of 500 microg of ObetaG 3 days prior to bacterial challenge. In conclusion, these studies demonstrated that ObetaG possesses immunomodulatory activities capable of stimulating immune functions both in vitro and in vivo.
Article
Full-text available
The processes of aging and photoaging are associated with an increase in cellular oxidation. This may be in part due to a decline in the levels of the endogenous cellular antioxidant coenzyme Q10 (ubiquinone, CoQ10). Therefore, we have investigated whether topical application of CoQ10 has the beneficial effect of preventing photoaging. We were able to demonstrate that CoQ10 penetrated into the viable layers of the epidermis and reduce the level of oxidation measured by weak photon emission. Furthermore, a reduction in wrinkle depth following CoQ10 application was also shown. CoQ10 was determined to be effective against UVA mediated oxidative stress in human keratinocytes in terms of thiol depletion, activation of specific phosphotyrosine kinases and prevention of oxidative DNA damage. CoQ10 was also able to significantly suppress the expression of collagenase in human dermal fibroblasts following UVA irradiation. These results indicate that CoQ10 has the efficacy to prevent many of the detrimental effects of photoaging.
Article
Full-text available
Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.
Article
The effect of intragastrically or parenterally administered β-glucan, extracted from oats, on the enhancement of disease resistance to Eimeria vermiformis was studied in mice. Groups of mice were immunosuppressed with dexamethasone (DXM), infected with oocysts of E. vermiformis and treated with oat β-glucan by the intragastric (i.g.) or subcutaneous (s.c.) routes. Faecal oocyst shedding was reduced in the β-glucan-treated groups compared to the non-treated group. Immunosuppressed mice which received no β-glucan treatment showed more severe clinical signs of the disease and a 50% mortality, while minimal clinical signs and no mortality were recorded in the β-glucan-treated groups. Total IgG, IgG1, IgG2a, IgM and IgA immunoglobulins in the serum of β-glucan-treated groups were overall higher than those in the non-treated group. Specific IgG anti-sporozoite and merezeite immunoglobulins in serum were significantly higher in the β-glucan-treated groups than in the non-treated aninals. No significant differences were found in the levels of intestinal IgA anti-sporozoite and anti-merozoite immunoglobulins. IFN-γ and IL-4-secreting cells, in response to sprozoite antigen, were detected in the spleen and mesenteric lymph nodes of the β-glucan-treated groups only. In conclusion, the i.g. and s.c. oat β-glucan treatment increased the resistance to E. vermiformis infection in immunosuppressed mice.
Article
Although topical applications of retinoids on rodents and humans have been shown to cause epidermal hyperplasia, a detailed study of the influence of retinoids on epidermal differentiation in vivo has not been performed. In order to assess the pharmacologic effects of chronic topical tretinoin application used to improve the appearance of patients with photoaged skin, cutaneous biopsies from 25 patients in a controlled clinical study were examined histologically and immunocytochemically. Chronic application of tretinoin causes epidermal thickening (25 of 25 samples), stratum granulosum thickening (15 of 25), parakeratosis (13 of 25), a marked increase in the number of cell layers expressing epidermal transglutaminase (13 of 25), and focal expression of two keratins, K6 (12 of 25) and K13 (8 of 25), not normally expressed in the epidermis. The morphologic changes correlated with immunohistochemical abnormalities; neither of these correlated with the subjective cosmetic response. Three major epidermal differentiation products, keratins K1, K10, and K14 were not altered, within the limits of the methods used. Thus, chronic topical tretinoin reprograms some, but not all, aspects of human epidermal differentiation in vivo.
Article
Immunomodulators that enhance macrophage function have been shown to be beneficial in a number of wound-healing models in humans and in experimental animals. The exact mechanism of this improved healing is unclear. To assess the role of collagen biosynthesis, the immunomodulator glucan phosphate was utilized in two murine models of wound healing, i.e., colon anastomosis and full-thickness skin incision. Tensile strength was evaluated using computer-assisted constant velocity tensiometry. Collagen biosynthesis was determined by assaying hydroxyproline content of wound hydrolysates by N-(9-fluorenyl)methoxycarbonyl/o-phthalaldehyde high-performance liquid chromatography. Experimental animals were treated with (1-3)-beta-D-glucan phosphate (250 mg/kg) intravenously 24 hours prior to colon anastomosis or skin incision. A second dose of glucan phosphate was given immediately postoperatively. Control animals received dextrose and water (5% w/v) intravenously. Tensile strength and hydroxyproline content were measured on postoperative Day 3. In the skin wound model, glucan phosphate treatment increased (P < 0.05) tensile strength by 42 per cent (342.5 +/- 12.2 vs 241.8 +/- 4.8 g), and hydroxyproline content was increased by 23.5 per cent (242.0 +/- 14.4 vs 196.8 +/- 10.5 pmol/microg; P < 0.05). In the glucan phosphate group, colon tensile strength was significantly (P < 0.05) increased by 34 per cent (34.2 +/- 2.3 g vs 45.8 +/- 2.1 g), and hydroxyproline content was increased by 7 per cent (47.45 +/- 3.31 vs 44.34 +/- 3.74 pmol/microg). These data indicate that macrophage modulation with glucan phosphate will increase tensile strength in experimental colon and skin wounds. In addition, we observed a positive correlation between glucan phosphate treatment, wound tensile strength, and collagen biosynthesis.
Article
The authors propose a treatment to improve skin texture and to decrease thin wrinkles and creases. The treatment is based on the use of 0.1% all-trans retinoic acid intradermic injections (with biopresence of 0.02%) combined with topic cream, immediately followed by 340 Nm blue light skin exposure. These procedures determine the retinoic binding protein stabilization that provides the acid intracellular penetration with its subsequent effects. An average of 10 sessions, once a week was required.
Article
We characterized the use of the fluorescent probe Sodium Green for measurements of intracellular free sodium using frequency-domain, phase-modulation fluorometry. The intensity decays were found to be strongly Na+ dependent, with mean lifetime increasing from 1.13 ns in the absence of Na+ to 2.39 ns in the presence of 140 mM Na+. Detailed analysis of the intensity decays in the presence of Na+ and K+ in the concentration range from 0 to 500 mM is provided. Sodium sensing using data measured at a single modulation frequency is described. Phase and modulation data showed high sensitivity to Na+ and substantially lower sensitivity to K+. Additionally, exposure of Sodium Green to intense illumination indicated that Sodium Green is much more photostable than its precursor, fluorescein. These results indicate that lifetime-based measurements with Sodium Green can be used for imaging of intracellular free [Na+] in the range from about 0.5 to 50 mM with high accuracy.