ArticlePDF Available

Effects of plant sterols derived from Aloe vera gel on human dermal fibroblasts in vitro and on skin condition in Japanese women

Authors:

Abstract and Figures

Aloe is known for its topical use for treating wounds and burns. Many previous studies reported the healing effects of Aloe vera. However, there are few clinical studies on the effect of orally administered A. vera gel on the skin. Aloe sterols are a type of plant sterols that have the capability to regulate the metabolism of glucose and lipids. In a recent study, we confirmed that ingested Aloe sterols reached the peripheral tissues through the bloodstream. However, their influence on dermal fibroblasts has not been investigated. First, we investigated the capability of Aloe sterols (cycloartenol and lophenol) to stimulate human dermal fibroblasts in vitro. Then, we investigated the effect of intake of Aloe vera gel powder (AVGP) containing 40 μg Aloe sterols on the skin conditions in Japanese women with dry skin in a randomized, double-blind, placebo-controlled trial. After cocultivation with Aloe sterols, the production of collagen and hyaluronic acid increased by approximately two-fold and 1.5-fold, and gene expression levels of these enzymes responsible for their synthesis were also observed in human dermal fibroblasts. An increase in arm skin hydration was observed at 8 weeks in the AVGP group, whereas a slight decrease in arm skin hydration was noted in the placebo group. However, there was no statistical difference between AVGP and placebo groups in skin moisture. In subgroup analysis, the change in the mean wrinkle depth was significantly lower in the AVGP group than in the control group. In addition, percent body fat after 8 weeks was significantly lower in the AVGP group. No AVGP intake-dependent harmful phenomenon was observed during the intake period. The present study confirms that daily oral Aloe sterol-containing AVGP significantly reduced facial wrinkles in women aged ≥40 years, and Aloe sterols stimulate collagen and hyaluronic acid production by human dermal fibroblasts.
Content may be subject to copyright.
© 2015 Tanaka et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0)
License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further
permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on
how to request permission may be found at: http://www.dovepress.com/permissions.php
Clinical, Cosmetic and Investigational Dermatology 2015:8 95–104
Clinical, Cosmetic and Investigational Dermatology Dovepress
submit your manuscript | www.dovepress.com
Dovepress
95
ORIGINAL RESEARCH
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/CCID.S75441
Effects of plant sterols derived from Aloe vera
gel on human dermal broblasts in vitro and
on skin condition in Japanese women
Miyuki Tanaka
1
Eriko Misawa
1
Koji Yamauchi
1
Fumiaki Abe
1
Chiaki Ishizaki
2
1
Functional Food Research
Department, Food Science and
Technology Institute, Morinaga Milk
Industry Co, Ltd, Zama, Kanagawa,
2
Ebisu Skin Research Center,
Inforward, Inc., Tokyo, Japan
Correspondence: Miyuki Tanaka
Functional Food Research Department,
Food Science and Technology Institute,
Morinaga Milk Industry Co, Ltd, 1-83,
Higashihara 5-Chome, Zama, Kanagawa
252-8583, Japan
Tel +81 046 252 3070
Fax +81 046 252 3049
Email m_tanaka@morinagamilk.co.jp
Background: Aloe is known for its topical use for treating wounds and burns. Many previous
studies reported the healing effects of Aloe vera. However, there are few clinical studies on
the effect of orally administered A. vera gel on the skin. Aloe sterols are a type of plant sterols
that have the capability to regulate the metabolism of glucose and lipids. In a recent study, we
confirmed that ingested Aloe sterols reached the peripheral tissues through the bloodstream.
However, their influence on dermal fibroblasts has not been investigated.
Methods: First, we investigated the capability of Aloe sterols (cycloartenol and lophenol) to
stimulate human dermal fibroblasts in vitro. Then, we investigated the effect of intake of Aloe
vera gel powder (AVGP) containing 40 μg Aloe sterols on the skin conditions in Japanese women
with dry skin in a randomized, double-blind, placebo-controlled trial.
Results: After cocultivation with Aloe sterols, the production of collagen and hyaluronic acid
increased by approximately two-fold and 1.5-fold, and gene expression levels of these enzymes
responsible for their synthesis were also observed in human dermal fibroblasts. An increase in
arm skin hydration was observed at 8 weeks in the AVGP group, whereas a slight decrease in
arm skin hydration was noted in the placebo group. However, there was no statistical difference
between AVGP and placebo groups in skin moisture. In subgroup analysis, the change in the
mean wrinkle depth was significantly lower in the AVGP group than in the control group. In
addition, percent body fat after 8 weeks was significantly lower in the AVGP group. No AVGP
intake-dependent harmful phenomenon was observed during the intake period.
Conclusion: The present study confirms that daily oral Aloe sterol-containing AVGP signifi-
cantly reduced facial wrinkles in women aged $40 years, and Aloe sterols stimulate collagen
and hyaluronic acid production by human dermal fibroblasts.
Keywords: aloe sterol, collagen, wrinkle
Introduction
Aloe vera (Aloe barbadensis Miller) is a plant species belonging to the family
Liliaceae.
1
A. vera gel is obtained from the mesophyll and has been used as a herbal
medicine.
2
The skin was raised and the recovery period was shortened by applying
A. vera gel in diabetic rats.
3
A clinical trial demonstrated the usefulness of A. vera for
the prophylaxis of radiation-induced dermatitis.
4
A. vera gel contains polysaccharides, amino acids, lipids, plant sterols, tannins,
and enzymes.
5,6
Acemannan is the major polysaccharide in A. vera gel and is known
to induce immunological responsiveness.
7,8
A previous report suggested that aceman-
nan stimulated the synthesis of keratinocyte growth factor-1 and vascular endothelial
growth factor by gingival fibroblasts in vitro.
9
However, the effects of other ingredients
in A. vera on dermal tissues have not been investigated.
Number of times this article has been viewed
This article was published in the following Dove Press journal:
Clinical, Cosmetic and Investigational Dermatology
20 February 2015
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
96
Tanaka et al
Fibroblasts represent the main cellular population of the
dermis. Their major function is to maintain extracellular
matrix (ECM) homeostasis.
10,11
The dermis tissues also
contain collagen, elastin, and hyaluronic acid (HA) as other
ingredients. Collagen forms the three-dimensional structure,
and elastin maintains the elasticity of the skin. HA is respon-
sible for moisture retention in the skin. Fibroblasts play an
important role in generating collagen, HA, and elastin in
the dermis.
Aloe sterols (lophenol [Lop], 24-methyl-lophenol, 24-ethyl-
lophenol, cycloartanol [Cyc], and 24-methylene-cycloartanol)
are plant sterols derived from A. vera gel and possess unique
efficacy.
12
Structurally, Aloe sterols fall into two groups of
compounds, the Lop group and the Cyc group. The oral
administration of Lop and Cyc reduced visceral fat accumu-
lation and improved hyperglycemia and hyperlipidemia in
animal models of diabetes and obesity.
13
However, the effect
of Aloe sterols on dermal cells and tissues is unknown. In
addition, although A. vera is known for its topical effect in
promoting wound healing, the active ingredient accounting
for the effect on the skin by oral administration has been not
considered in detail. Therefore, the aim of the present study
was to investigate the effect of Aloe sterols on human dermal
fibroblasts in vitro. Next, we examined the influence of the
intake of Aloe vera gel powder (AVGP) containing Aloe sterols
on the skin conditions in Japanese women with dry skin.
Materials and methods
Cell cultures
Primary adult human dermal fibroblasts (HDFa #2320)
were obtained from DS Pharma Biomedical (Tokyo, Japan).
The cell cultures were maintained in CSC complete serum-
free medium system (Cell Systems Corporation, Kirkland,
WA, USA). They were seeded at 5×10
4
cells/well in 12-well
plates and cultured. After 48 hours, cells were incubated
for another 48 hours in the absence or presence of Cyc
and Lop. RNA was extracted from fibroblasts after 6-hour
cultivation, and the culture supernatant was collected after
48 hours. The collagen and HA contents of the supernatant
were determined using a soluble collagen assay (Accurate
Chemical and Scientific Corporation, Westbury, NY, USA)
and HA ELISA assay kit (R&D Systems Inc., Minneapolis,
MN, USA).
Cell proliferation assay
Cell viability was assessed by culturing cells in a culture
medium containing 10% WST-8 (Dojin Molecular Technolo-
gies, Kumanoto, Japan) for 0 hour to 6 hours at 37°C and was
obtained by scanning with a microplate reader at 492 nm.
This absorbance was expressed as a percentage of that in the
control cells, after subtraction of background absorbance.
Real-time reverse transcription polymerase
chain reaction (RT-PCR) analysis
Total RNA was extracted from human dermal fibroblasts with
the RNeasy Mini Kit (Qiagen NV, Venlo, the Netherlands)
according to the manufacturers protocol. Its quality was verified
by lab-on-a-chip analysis (2100 Bioanalyzer; Agilent Technolo-
gies, Santa Clara, CA, USA). Total RNA was used for one-cycle
RNA synthesis (Affymetrix, Santa Clara, CA, USA) with the
PrimeScript 1st strand cDNA Synthesis Kit (Takara Bio, Otsu,
Japan). Then, real-time PCR primer sets were purchased from
the Takara Bio Perfect Real Time Support System. Real-time
PCR was performed using Fast SYBR
®
Green Master Mix
(product line of Thermo Fisher Scientific, Waltham, MA, USA)
or TaqMan
®
Fast Universal PCR Master Mix (product line of
Thermo Fisher Scientific) on a 7500 Fast Real-Time PCR Sys-
tem (product line of Thermo Fisher Scientific). Melting curve
analysis showed a single melting curve in each RT-PCR assay
using Fast SYBR Green (Figure S1). mRNA expression levels
of all genes were normalized to those of β-actin (Cell Signaling
Technology, Tokyo, Japan) in the same sample. The differences
between the control and Aloe sterol-treated fibroblasts were
expressed as relative increases, with the control value set to
100%. The results are expressed as mean ± standard deviation
(SD) of three independent experiments.
Preparation and composition
of the AVGP tablets
AVGP (Lot 20111027) was prepared by Morinaga Milk
Industry Co Ltd (Tokyo, Japan) by drying the mesophyll
of A. vera plants cultivated at Thai farms. The composi-
tions of AVGP and the control tablets are presented in
Table 1. In the placebo tablets, AVGP was replaced by
inert dextrin. The amount of Aloe sterols per daily dose
(five tablets; 0.5 g AVGP) was approximately 40 μg (Lop,
24-methyl-lophenol, 24-ethyl-lophenol, cycloartanol, and
24-methylene-cycloartanol were 11, 13, 5, 6, and 8 μg,
respectively), as determined by liquid chromatography–
tandem mass spectrometry analysis.
Human study design
This double-blinded, placebo-controlled trial was performed
from September to December 2012 at the Ceravi Shinbashi
Clinic (Tokyo, Japan) by the KSO Corporation Co, Ltd
(Tokyo, Japan). The skin parameters were measured by the
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
97
Aloe sterols impact on skin conditions in Japanese women
Table 1 Ingredient composition of study tablets
Placebo
(mg/5 tablets)
AVGP
(mg/5 tablets)
AVGP 0 500
Dextrin 500 0
Citric acid 100 100
Maltose 1,417.5 1,417.5
Sour milk 25 25
Cellulose 250 250
Calcium phosphate 12.5 12.5
Flavor 87.5 87.5
Glycerin fatty acid 50 50
Sugar ester 50 50
Food color 5 5
Abbreviation: AVGP, Aloe vera gel powder.
Skin Research Center of InfoWard Inc. (Tokyo, Japan). A total
of 58 Japanese women with dry skin (age: 20–50 years) were
randomly assigned to the placebo (n=28) or AVGP (n=28)
group. We defined dry skin by an amount value of 60 AU
or less for cheek moisture (measured by Corneometer CM
825 [Courage and Khazaka, Cologne, Germany]). Each
participant was identified by a code randomly selected by
a computer-generated permutation procedure. The codes
were allocated sequentially in the order in which participants
were enrolled. After all measurements were completed, the
randomization code was disclosed to investigators. Study
participants, investigators, study staff members, and labora-
tory technicians were blinded to the group assignment. All
participants provided written informed consent to participate
before beginning the study and were free to withdraw from
the study at any time without obligation. The study protocol
was examined and approved by the institutional review board
of Ceravi Shinbashi Clinic, and was conducted according to
the guidelines of the Declaration of Helsinki.
Dosage regimen
All subjects ingested five tablets per day (AVGP or placebo)
for 8 weeks. Assessments of skin parameters and general
physical examinations (ie, height, weight, and percent body
fat) were conducted at weeks 0, 4, and 8 of the treatment
period. Vital signs (heart rate and blood pressure) and labora-
tory analyses (hematology, blood chemistry, and urinalysis)
were performed at each visit.
Measurements of skin parameters
The hydration properties of the skin and crows feet
wrinkles were measured by noninvasive methods at weeks
0, 4, and 8 of the treatment period. Measurements were
performed under standard conditions of room temperature
(20°C–22°C) and humidity (45%–55%). Participants were
given at least 20 minutes before the examination to adapt
to the room conditions. Skin wrinkles were measured using
a two-dimensional analysis system of replicas at oblique
illumination. Participants were seated and instructed to keep
their eyes closed. Skin replicas were obtained according to
the guidelines of the Japan Cosmetic Industry Association.
Silicone skin replicas were taken from the left crow’s feet
region 5 mm from the lateral angle of the eye. Corneometer
CM 825 was used to determine the skin hydration level of the
inner side of one upper arm and one cheek. Percent body fat
was measured by impedance using body weight composition
(Omron, Tokyo, Japan).
Statistical analysis
Typically, dermatological studies assess skin changes over
time in comparison with baseline parameters. During this
8-week study, descriptive statistics were calculated at each
time point (weeks 0, 4, and 8). For all variables, differences
between baseline and weeks 4 and 8, but not between weeks 4
and 8, were calculated. Analysis of covariance was performed
for absolute skin hydration levels and the maximal width
of the largest wrinkle and mean depth of wrinkles. The
percentage of change in skin wrinkle parameters and percent
body fat were calculated using the following equation:
([treatment period baseline value]/baseline values) ×100.
Analyses were performed using SPSS Statistics 17.0.
A P-value ,0.05 was considered significant. The changes
in skin wrinkle parameters are expressed as mean ± standard
error or the mean (SEM) and the other data as mean ± SD.
Results
Fibroblasts produce major skin components, including col-
lagen and HA. Therefore, cultured human fibroblasts were
used to test the ability of Aloe sterols to stimulate collagen
and HA production by human dermal fibroblasts. After a
48-hour coculture, Cyc and Lop increased collagen and HA
production by cultured human fibroblasts in a concentration-
dependent manner (Figure 1A and B). Treatment with 2 μM
Aloe sterols increased collagen production in comparison
with control (Cyc: 1.77±0.1, Lop: 1.4±0.06 vs control:
0.9±0.01 μg/mL) (Figure 1A). Similarly, treatment with
2 μM Cyc and Lop increased HA production in compari-
son with control (Cyc: 118.33±1.53, Lop: 107.69±2.28 vs
control: 69.17±0.76 ng/mL) (Figure 1B). We did not observe
a change in cell viability after the addition of Cyc and Lop
(Figure 1C). These data suggest that the effects of sterols on
human fibroblasts are specific for A. vera.
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
98
Tanaka et al
00
0
20
40
60
80
100
50
100
150
**
**
**
**
**
*
0.02
Con Cyc Lop
0.2 2 0.02 0.2 2 µM 0.02
Con Cyc Lop
0.2 2 0.02 0.2 2 µM
0.02
Con Cyc Lop
0.2 2 0.02 0.2 2 µM
0.5
1
Collagen (µg/mL)
Cell viability (%)
HA (ng/mL)
1.5
2
AB
C
**
*
*
*
Figure 1 Effects of Aloe sterols on (A) collagen and (B) HA production in human dermal broblasts. Cells were incubated for 48 hours in the absence or presence of
0.02–2 μM Cyc and Lop. The collagen and HA contents of the culture supernatant were determined with a soluble collagen assay and an HA ELISA assay kit. Cell viability
was assessed by WST-8 (C).
Notes: The data are expressed as the mean ± SD (n=3). *P,0.05 and **P,0.001 vs control (0 μM).
Abbreviations: HA, hyaluronic acid; Con, control; Cyc, cycloartenol; Lop, lophenol; ELISA, enzyme-linked immunosorbant assay; SD, standard deviation.
The mechanism of stimulation by Aloe sterols was deter-
mined by measuring the expression level of key enzymes
responsible for collagen (COL1A1 and COL3A1) and HA
(HAS2 and HAS3) production by human fibroblasts. A 6-hour
incubation period with 0.02–2.0 μM Cyc and Lop was asso-
ciated with a dose-dependent increase in the mRNA level of
all four enzymes (Figure 2).
A double-blinded, placebo-controlled trial was conducted
to determine whether the oral ingestion of AVGP containing
Aloe sterols can significantly improve dry skin. A total of
56 women with dry skin were randomly assigned to the pla-
cebo group or the AVGP group. One participant in each group
withdrew after the baseline tests. Therefore, we analyzed the
data from 54 subjects. The two groups presented comparable
baseline characteristics (Table 2). They had healthy women
in their 40s, with a low incidence of smoking, and about half
of them drank alcohol. There was no difference in the rate
of tablet intake between placebo (96.1%±18.9%) and AVGP
(99.6%±1.6%) groups. No significant treatment-related
adverse events were reported during the 8-week study (data
not shown).
The facial skin hydration levels at 8 weeks were signifi-
cantly increased in both groups compared with the baseline
levels (Table 3). An increase in arm skin hydration was
observed at 8 weeks in the AVGP group, whereas a slight
decrease in arm skin hydration was observed in the placebo
group. No significant differences were observed in skin
hydration at both sites between the groups.
The changes in the maximal width of the largest wrinkle
and mean wrinkle depth from the baseline value after 4 weeks
and 8 weeks of treatment are shown in Table 4. In the placebo
group, the percent change in the maximal width of the largest
wrinkle and mean wrinkle depth from baseline increased at
8 weeks (3.96%±4.23% and 0.73%±0.96%, respectively),
whereas the values were lower at 8 weeks compared with
those at baseline in the AVGP group (2.18%±4.09%
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
99
Aloe sterols impact on skin conditions in Japanese women
0
0.02
Con Cyc Lop
0.2 2 0.02 0.2 2 µM
0.02
Con Cyc Lop
0.2 2 0.02 0.2 2 µM 0.02
ConCyc Lop
0.2 2 0.02 0.2 2 µM
0.02
ConCyc Lop
0.2 2 0.02 0.2 2 µM
0.5
1
COL3A1 mRNA
COL1A1 mRNA
1.5
2
COL3A1
HAS2 HAS3
COL1A1
0
0.5
1
1.5
*
*
*
**
*
*
*
*
*
*
*
**
**
**
**
**
**
**
**
**
*
**
**
0
0.5
1
HAS2 mRNA
HAS3 mRNA
1.5
2
2.5
0
0.5
1
1.5
2
2.5
Figure 2 Effects of Aloe sterols on the gene expression of enzymes responsible for the synthesis of collagen (COL1A1 and COL3A1) and HA (HAS2 and HAS3) in human
dermal broblasts.
Notes: Cells were incubated for 6 hours in the absence or presence of 0.02–2 μM and 0.02–2 μM Cyc and lophenol (Lop), and changes in gene expression relative to control
(0 μM) were determined by qRT-PCR. The data are expressed as mean ± SD (n=3). *P,0.05 and **P,0.001 vs control.
Abbreviations: Con, control; Cyc, cycloartenol; Lop, lophenol; qRT-PCR, real-time reverse transcription polymerase chain reaction; SD, standard deviation.
group was 1.18%±5.85% vs 10.70%±4.65% in the AVGP
group (Figure 3A). Furthermore, the percent change in the
mean wrinkle depth was significantly lower in the AVGP
group than in the placebo group at 8 weeks in this age group
(P=0.035) (Figure 3B). In contrast, both parameters were not
significantly affected by the placebo.
Figure 4 presents typical changes in a replica image in four
participants (two from each group) before and after 8 weeks
of treatment with the AVGP supplement or placebo.
The oral AVGP and placebo regimens did not affect body
weight (Table 5). In contrast, the mean percent body fat in
the AVGP group was significantly lower compared with the
placebo group after 8 weeks (P=0.036). When the data are
expressed relative to baseline values for each subject, AVGP
did not affect percent body fat, whereas the placebo induced
a significant increase in percent body fat (P=0.037).
Discussion
Skin aging is caused by repeated exposure to UV radiation
(photoaging) or by naturally occurring biological pro-
cesses (intrinsic aging). The skin collagen content declines
Table 2 Demographic and baseline characteristics
Placebo (n=27) AVGP (n=27)
P-value
Number or
mean ± SD
Number or
mean ± SD
Age
a
(range), years
37.8±6.9 39.7±5.0
0.254
Height
a
(cm)
158.4±5.8 159.3±5.2
0.565
Body weight
a
(kg)
53.6±11.2 53.6±10.7
0.999
BMI
a
(kg/m
2
)
21.3±3.9 21.1±4.1
0.867
Systolic blood
pressure
a
(mmHg)
108.5±11.7 106.3±11.0
0.467
Diastolic blood
pressure
a
(mmHg)
67.3±9.1 66.9±8.4
0.868
Pulse rate
a
(bpm)
71.6±11.0 70.9±9.6
0.798
Smoker
b
3 2 1
Drinker
b
17 12 0.285
Notes:
a
Data are expressed as mean ± SD;
b
data are expressed as numbers of
persons.
Abbreviations: AVGP, Aloe vera gel powder; BMI, body mass index.
and 0.11%±1.0%). However, the differences in both
groups were not significant. Next, we performed a stratified
analysis of subjects aged $40 years (placebo group, n=12,
and AVGP group, n=14). The percent change in the maxi-
mal width of the largest wrinkle at 8 weeks in the placebo
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
100
Tanaka et al
Table 3 Skin hydration of face and arm in women who ingested AVGP or placebo tablets
Item Group n Baseline value
(0 week)
4 weeks 8 weeks
Mean ± SD Mean ± SD
ANCOVA Paired t
Mean ± SD
ANCOVA Paired t
Skin hydration AVGP 27
29.0±10.8 30.3±11.6
0.055
36.8±12.4
0.846
Face (AU) Placebo 27
30.4±8.7 34.4±7.6 37.5±10.6
∆ skin hydration AVGP 27
1.2±5.2
0.223
7.7±7.3
0.000*
Face Placebo 27
4.0±6.5
0.004*
7.1±8.8
0.000*
Skin hydration AVGP 27
35.4±6.6 36.4±6.1
0.992
37.6±6.8
0.671
Arm (AU) Placebo 27
38.7±6.4 39.1±9.0 38.4±8.7
∆ skin hydration AVGP 27
1.0±4.0
0.230
2.2±6.7
0.108
Arm Placebo 27
0.4±6.7
0.741
0.3±8.4
0.878
Notes: Data are expressed as mean ± SD. *Different from week 0.
Abbreviations: AVGP, Aloe vera gel powder; SD, standard deviation; ANCOVA, analysis of covariance; AU, arbitrary unit.
Table 4 Analysis results of the wrinkle replicas
Item of wrinkle Group n Baseline value
(0 week)
4 weeks 8 weeks
Mean ± SD Mean ± SD
ANCOVA Paired t
Mean ± SD
ANCOVA Paired t
Maximal largest
width (μm)
AVGP 27
481.0±135.9 510.3±174.4
0.608
469.2±179.3
0.817
Placebo 27
481.8±214.5 493.6±219.4 476.7±187.3
∆ maximal
largest width
AVGP 27
29.2±126.0
0.238
12.0±124.5
0.622
Placebo 27
11.8±123.6
0.624
5.2±99.7
0.789
Mean depth (μm)
AVGP 27
160.2±23.1 159.9±24.1
0.873
159.9±24.1
0.564
Placebo 27
162.4±26.7 161.6±25.4 163.4±27.1
∆ mean depth AVGP 27
0.28±10.2
0.888
0.29±8.46
0.860
Placebo 27
0.83±7.7
0.579
0.98±9.32
0.546
Note: Data are expressed as mean ± SD.
Abbreviations: SD, standard deviation; ANCOVA, analysis of covariance; AVGP, Aloe vera gel powder.
significantly with age in people aged $40 years and after
menopause.
14
Aging causes a reduction in skin collagen
synthesis by at least two mechanisms: cellular fibroblast
aging and a lower level of mechanical stimulation.
15
In the
dermis, heterotypic collagen fibrils contain mainly type I and
type III collagens. The major function of type III collagen
is associated with the fibrogenesis of type I collagen.
16
Type
III collagen is abundant at sites of healing and repair in the
skin and other tissues. COL1A1 produces a component of
type I collagen, whereas COL3A1 produces a component
of type III collagen. In this study, we confirmed that Aloe
sterols promote the production of collagen and increase the
gene expression level of type I and type III collagen syn-
thesis in human dermal fibroblasts. To observe the effects
of Cyc and Lop to collagen and HA synthesizing enzyme at
the protein level, Western blot analysis was performed. As
shown in Figure S2, COL3A1 expression in human dermal
fibroblasts was upregulated by Aloe sterols at the protein
level. However, further examination is necessary to elucidate
effect of Aloe sterols to protein level of COL1A1. This result
suggests that Aloe sterols affect the ECM structure of the
dermis layer.
Dermal fibroblasts also synthesize HA, which plays an
important role in skin hydration. Age-related declines in
total HA production have been documented in human skin.
1
The synthesis of HA is accomplished by three isoforms of
hyaluronan synthase: HAS1, HAS2, and HAS3. Almost all
known regulatory systems induce HA synthesis, including
growth factors and cytokines. In the present study, Aloe ste-
rols stimulated HA production and gene expression of HA
synthesis in human dermal fibroblasts. The protein levels of
HAS2 and HAS3 of dermal fibroblasts were also increased by
Aloe sterols (Figure S2). These data suggest that Aloe sterols
have the capability to improve skin moisture by increasing
the HA content in the dermal ECM.
Adiponectin is a novel adipocyte-specific protein with
important insulin-sensitizing, anti-atherogenic,
17
and anti-
inflammatory
18
properties. A recent study indicated that skin
adiponectin was found in plasma, subcutaneous adipose
tissue, and dermal sebaceous tissue.
19
Adiponectin promoted
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
101
Aloe sterols impact on skin conditions in Japanese women
HA synthesis and increased HAS2 mRNA level through an
AMPK/PPARα-dependent signaling pathway in human dermal
fibroblasts.
20
We previously showed that the oral administra-
tion of Aloe sterols caused an increase in serum adiponectin
level.
13
In Apc-deficient Min/+ mice, the ingestion of A. vera
gel supercritical CO
2
extract induced an increase in the serum
level of high-molecular-weight adiponectin.
21
We recently
initiated a new study to determine the effect of Aloe sterols
on adiponectin in the epidermis, dermis, and fat tissues. In
our latest study, using hairless mice, which we irradiated with
UVB light, we confirm that adiponectin level in serum and
gene expression level of HAS2 of mouse skin were increased
by AVGP intake (Saitou M, unpublished data, 2015).
We present results from the first randomized, double-blind,
placebo-controlled trial on the effects of oral A. vera gel sup-
plementation for dry skin in Japanese women. The placebo
and AVGP groups responded to treatment by an increase in
facial moisture. This study was conducted during the peak
season for dry skin: from September to December. The
continual use of facial cosmetics during the testing period
could explain these findings. We recognized that cosmetics
affect mainly the epidermis. On the other hand, oral inges-
tion of AVGP was expected to act on the dermis through the
blood. Therefore, we did not stop the use of cosmetics on
the subject. Therefore, in order to examine the effect of oral
ingestion of AVGP to face moisture content, additional study
of subjects that do not use the cosmetics is required. On the
other hand, arm skin moisture decreased in the placebo group
and increased in the AVGP group, but these responses were
not statistically significant. Thus, the possible moisturizing
–20 –5
–2.5
0
2.5
5
04
Weeks
804
*P=0.035
*
Weeks
8
–10
0
% change
% change
10
20
AB
Placebo
AVGP
Placebo
AVGP
Figure 3 Effects of oral AVGP therapy on the facial wrinkles of participants with dry skin aged $40 years.
Notes: Participants ingested placebo or AVGP tablets containing Aloe sterols for 8 weeks, and measurements were taken after 0 week, 4 weeks, and 8 weeks of therapy.
(A) Maximal width of the largest wrinkle (mean ± SEM). (B) Mean wrinkle depth (mean ± SD). , placebo group, n=12; , AVGP group, n=14. *P=0.035 vs placebo.
Abbreviations: AVGP, Aloe vera gel powder; SEM, standard error of the mean; SD, standard deviation.
Placebo
Placebo
AVGP
AVGP
Baseline Week 8
Figure 4 Effects of oral AVGP therapy facial skin hydration.
Notes: Participants ingested placebo or AVGP tablets containing Aloe sterols for
8 weeks, and measurements were taken after 0 week and 8 weeks. Silicone skin
replicas of the left crow’s feet were analyzed with a corneometer to determine the skin
hydration level. The images present typical replicas for two subjects of each group.
Abbreviation: AVGP, Aloe vera gel powder.
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
102
Tanaka et al
Table 5 Values and changes of body weight and body fat percentage 4 weeks and 8 weeks after treatment
Item Group n Baseline value
(0 week)
4 weeks 8 weeks
Mean ± SD Mean ± SD
ANCOVA Paired t
Mean ± SD
ANCOVA Paired t
Body weight (kg) AVGP 27
53.8±10.7 53.9±10.8
0.511
53.7±10.9
0.474
Placebo 27
53.7±11.9 54.0±11.5 53.5±10.7
∆ body weight AVGP 27
0.1±1.1
0.539
0.2±1.2
0.523
Placebo 27
0.3±1.2
0.153
0.2±2.1
0.640
Body fat
percentage (%)
AVGP 27
27.7±6.1 27.3±6.0
0.051
27.3±6.3
0.036
a
Placebo 27
27.9±4.9 28.1±4.9 28.3±4.6
∆ body fat
percentage
AVGP 27
0.4±1.2
0.141
0.4±1.7
0.279
Placebo 27
0.2±1.0
0.207
0.5±1.1
0.037
b
Notes: Data are expressed as mean ± SD.
a
P=0.036 vs placebo;
b
P=0.037 vs week 0.
Abbreviations: SD, standard deviation; ANCOVA, analysis of covariance; AVGP, Aloe vera gel powder.
benefits of AVGP would not supplement the regular use of
facial and body creams. On the other hand, we demonstrate
that daily oral AVGP (40 μg of Aloe sterols) significantly
reduced facial wrinkles in women aged $40 years in terms
of the mean wrinkle depth. The depth of wrinkles rapidly
increased in women aged $40 years.
22
Thus, the daily oral
intake of AVGP could reduce skin aging by targeting wrinkles
rather than by acting as a systemic moisturizing agent.
An animal study showed that AVGP ingestion signifi-
cantly reduced subcutaneous and visceral fat weight, and
percent body fat in diet-induced obese rats.
23
The present
study showed, for the first time, that oral AVGP caused a
significant reduction in percent body fat in human subjects.
However, additional testing using suitable candidates
(overweight person, etc) for examining the effect of AVGP on
body fat is required. We recently demonstrated the contribu-
tion of Aloe sterols in the gel powder in an animal model of
type 2 diabetes.
24
The Aloe sterols Cyc and Lop improved
fatty acid metabolism in the liver by upregulation of many
genes targeted by PPARs. To confirm the anti-obesity effect
of AVGP containing Aloe sterols, it is necessary to conduct
clinical tests on overweight or obese subjects.
A. vera whole leaf may contain anthraquinones, which
have been shown to generate reactive oxygen species in
the presence of UVA light. Exposure to UVA light can
also generate reactive oxygen species and is associated
with photo-damaged and photo-aged skin in humans.
25
A. vera gel, which is taken from the leaf, does not include
anthraquinones. Furthermore, we confirmed that the AVGP
tablet did not include anthraquinones before carrying out
this examination. In this study, there were less signs indi-
cating dermal irritancy due to AVGP intake, as per the skin
diagnosis performed by a dermatologist on each subject
during the testing period. We previously tested the safety of
AVGP in vitro and in vivo. In a 90-day toxicity test in which
rats were continuously administered AVGP at 1,328 mg/kg,
euthanized, and subjected to pathological examinations,
no abnormalities attributable to the AVGP were found.
AVGP was non-mutagenic in either the Ames test or in
a chromosomal aberration test at concentrations of up to
5,000 μg/plate, or in an in vivo bone marrow micronucleus
test at up to 2,000 mg/kg/d. Therefore, AVGP can be safely
used as a functional food material.
In conclusion, the present study showed that Aloe sterols
stimulated collagen and HA production by human dermal
fibroblasts, and that AVGP containing Aloe sterols reduced
facial wrinkles in women. More recently, we confirmed that
ingested Aloe sterols reached the peripheral tissues through the
bloodstream (Ikeda I, unpublished data, 2010). Together, these
data suggest that AVGP alters skin metabolism in vivo. We are
currently testing the protective efficacy of Aloe sterols against
skin damage by UV radiation. Future studies are also required to
elucidate the protective mechanism of Aloe sterols in the skin.
Disclosure
The authors report no conflicts of interest in this work.
References
1. Grindlay D, Reynolds T. The Aloe vera phenomenon: a review of the
properties and modern uses of the leaf parenchyma gel. J Ethnopharmacol.
1986;16:117–151.
2. Little JW. Complementary and alternative medicine: impact on den-
tistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98:
137–145.
3. Chithra P, Sajithlal GB, Chandrakasan G. Influence of Aloe vera on the
healing of dermal wounds in diabetic rats. J Ethnopharmacol. 1998;59:
195–201.
4. Heggie S, Bryant GP, Tripcony L, et al. A Phase III study on the efficacy
of topical Aloe vera gel on irradiated breast tissue. Cancer Nurs. 2002;25:
442–451.
5. Shelton RM. Aloe vera. Its chemical and therapeutic properties. Int J
Dermatol. 1991;30:679–683.
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
103
Aloe sterols impact on skin conditions in Japanese women
6. Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical
effectiveness. Br J Gen Pract. 1999;49:823–828.
7. Zhang L, Tizard IR. Activation of a mouse macrophage cell line
by acemannan: the major carbohydrate fraction from Aloe vera gel.
Immunopharmacology. 1996;35:119–128.
8. Djeraba A, Quere P. In vivo macrophage activation in chickens with
Acemannan, a complex carbohydrate extracted from Aloe vera. Int J
Immunopharmacol. 2000;22:365–372.
9. Jettanacheawchankit S, Sasithanasate S, Sangvanich P, Banlunara W,
Thunyakitpisal P. Acemannan stimulates gingival fibroblast proliferation;
expressions of keratinocyte growth factor-1, vascular endothelial growth
factor, and type I collagen; and wound healing. J Pharmacol Sci.
2009;109:525–531.
10. Sorrell JM, Caplan AI. Fibroblast heterogeneity: more than skin deep.
J Cell Sci. 2004;117:667–675.
11. Sorrell JM, Caplan AI. Fibroblast – a diverse population at the center
of it all. Int Rev Cell Mol Biol. 2009;276:161–214.
12. Tanaka M, Misawa E, Ito Y, et al. Identification of five phytosterols from
Aloe vera gel as anti-diabetic compounds. Biol Pharm Bull. 2006;29:
1418–1422.
13. Misawa E, Tanaka M, Nomaguchi K, et al. Administration of phytos-
terols isolated from Aloe vera gel reduce visceral fat mass and improve
hyperglycemia in Zucker diabetic fatty (ZDF) rats. Obes Res Clin Pract.
2008;2:239–245.
14. Castelo-Branco C, Pons F, Gratas E, Fortuny A, Vanrell JA,
González-Merlo J. Relationship between skin collagen and bone
changes during aging. Maturitas. 1994;18:199–206.
15. Varani J, Dame MK, Rittie L, et al. Decreased collagen production in
chronologically aged skin. Am J Pathol. 2006;168:1861–1868.
16. Liu X, Wu H, Byrne M, Krane S, Jaenisch R. Type III collagen is
crucial for collagen I fibrillogenesis and for normal cardiovascular
development. Proc Natl Acad Sci U S A. 1997;94:1852–1856.
17. Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the
family of soluble defense collagens, negatively regulates the growth of
myelomonocytic progenitors and the functions of macrophages. Blood.
2000;96:1723–1732.
18. Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein,
adiponectin, suppresses lipid accumulation and class A scavenger recep-
tor expression in human monocyte-derived macrophages. Circulation.
2001;103:1057–1063.
19. Akazawa Y, Sayo T, Sugiyama Y, et al. Adiponectin resides in mouse
skin and upregulates hyaluronan synthesis in dermal fibroblasts.
Connect Tissue Res. 2011;52:322–328.
20. Yamane T, Kobayashi-Hattori K, Oishi Y. Adiponectin promotes
hyaluronan synthesis along with increases in hyaluronan synthase
2 transcripts through an AMP-activated protein kinase/peroxisome
proliferator-activated receptor-α-dependent pathway in human
dermal fibroblasts. Biochem Biophys Res Commun. 2011;18(415):
235–238.
21. Chihara T, Shimpo K, Beppu H, et al. Reduction of intestinal polyp
formation in min mice fed a high-fat diet with Aloe vera gel extract.
Asian Pac J Cancer Prev. 2013;14:4435–4440.
22. Akazaki S, Nakagawa H, Kazama H, et al. Age-related changes in skin
wrinkles assessed by a novel three-dimensional morphometric analysis.
Br J Dermatol. 2002;147:689–695.
23. Misawa E, Tanaka M, Nabeshima K, et al. Administration of dried Aloe
vera gel powder reduced body fat mass in diet-induced obesity (DIO)
rats. J Nutr Sci Vitaminol. 2012;58:195–201.
24. Nomaguchi K, Tanaka M, Misawa E, et al. Aloe vera phytosterols act
as ligands for PPAR and improve the expression levels of PPAR target
genes in the livers of mice with diet-induced obesity. Obes Res Clin
Pract. 2011;5:e169–e266.
25. Xia Q, Yin JJ, Fu PP, Boudreau MD. Photo-irradiation of Aloe vera
by UVA formation of free radicals, singlet oxygen, superoxide,
and induction of lipid peroxidation. Toxicol Lett. 2007;168(2):
165–175.
Clinical, Cosmetic and Investigational Dermatology
Publish your work in this journal
Submit your manuscript here: http://www.dovepress.com/clinical-cosmetic-and-investigational-dermatology-journal
Clinical, Cosmetic and Investigational Dermatology is an interna-
tional, peer-reviewed, open access, online journal that focuses on
the latest clinical and experimental research in all aspects of skin
disease and cosmetic interventions. All areas of dermatology will
be covered; contributions will be welcomed from all clinicians and
basic science researchers globally. This journal is indexed on CAS.
The manuscript management system is completely online and includes
a very quick and fair peer-review system, which is all easy to use.
Visit http://www.dovepress.com/testimonials.php to read real quotes
from published authors.
Clinical, Cosmetic and Investigational Dermatology 2015:8
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
Dovepress
104
Tanaka et al
Supplementary materials
–0.100
60 65 70 75
Temperature (˚C)
80 85 90 95
Cetector = HAS2
Well(s): A1-H12
Document: 141119-1 (Standard curve)
Cetector = HAS2
Well(s): A1-H12
Document: 141119-1 (Standard curve)
Cetector = HAS2
Well(s): A1-H12
Document: 141119-1 (Standard curve)
60 65 70 75
Temperature (˚C)
80 85 90 95 60 65 70 75
Temperature (˚C)
80 85 90 95
0.000
0.100
0.200
0.300
Derivative
Derivative
Derivative
0.400
0.500
–0.100
0.000
0.100
0.200
0.300
0.400
0.500
–0.100
0.000
0.100
0.200
0.300
0.400
0.5000.600
Dissociation curve Dissociation curve Dissociation curve
COL3A1 HAS2 HAS3
Figure S1 Melting curve analysis of qRT-PCR assay.
COL3A1
Con Cyc Lop Con Cyc Lop Con Cyc Lop
β-actin
HAS2
β-actin
HAS3
β-actin
Figure S2 Effect by Cyc and Lop in COL3A1, HAS2, and HAS3 expression at the protein level (Western blot analysis).
Notes: Cells were incubated for 6 hours in the absence or presence of 2 μM Cyc and Lop. Western blot analysis was performed using monoclonal antibodies: COL3A1
(abcam
®
), HAS2 (abcam
®
) and HAS3 (abcam
®
), and β-actin abcam
®
(Cambridge, England, United Kingdom).
Abbreviations: Con, control; Cyc, cycloartenol; Lop, lophenol.

Supplementary resources (2)

... It has been shown to reduce the time required for wound healing and infection [7,8]. Tanaka et al. discovered that co-cultivating aloe sterols (Cyc and Lop) with human dermal fibroblasts increased collagen and hyaluronic acid production while maintaining cell viability [9]. ...
... Oryan et al., in 2019, investigated the effects of Aloe vera hydrogel loaded with allogeneic adipose stem cells (ASC) on a rat burn wound model and found that aloe vera/ASC-treated wounds had reduced inflammatory response on day 7, enhanced angiogenesis and reepithelialization on day 14, and subsequently reduced scar formation when compared to other groups [17]. Furthermore, several studies show that aloe vera provides a favorable environment for stem cell adhesion and proliferation and induces host stem cell migration and angiogenesis has been proven to have a synergistic effect in wound healing with stem cells [8,9,16,17]. We found that the A-PCL construct was easy to prepare and apply. ...
Article
PurposeBurn injury is an escalating epidemic with devastating short- and long-term consequences. Stem cell therapy presents a novel therapeutic strategy for skin repair and regeneration. This study compares the regeneration of epidermal and dermal components with the use of human Wharton’s jelly mesenchymal stem cells (WJ-MSCs) on a novel aloe vera-polycaprolactone (A-PCL) composite scaffold and collagen sheet in a rat burn model.Methods Stem cells from Wharton jelly were isolated, cultured, and characterized using flow cytometry. A-PCL sheets were fabricated in house using the solvent casting method. Cells at passage 1(1 × 105 cm2) were seeded on A-PCL and collagen sheets. Four-square centimeter in vivo rat burn model was established by applying a heated coin over the back for 30 s without external pressure to achieve a deep dermal burn. Experimental groups (n = 7 each) were burn control, collagen alone, A-PCL alone, collagen-WJ-MSCs, and A-PCL-WJ-MSCs. Outcome was assessed by gross appearance (Bates Jensen and Vancouver scar scale (VSS)) and histology.ResultsCulture expanded MSCs were characterized positive for human cell surface markers. The wound remained unhealed in the burn control group at day 28 with a Bates Jensen score of 18. The other four arms healed with the fastest healing occurring in the A-PCL-WJ-MSCs group with the best VSS. The burns control group showed the unhealed ulcer with inflammation and fibrosis. Both collagen groups (with and without cells) showed complete restoration of epidermal continuity with few regenerated hair follicles. The inflammation was mild, but fibrosis is prominent. The A-PCL group showed complete epithelization with inflammation and dense fibrosis like the control group. Aloe-PCL-WJ-MSC-treated animal shows complete epidermal restoration and near-normal regeneration of hair follicles and sebaceous glands. Fibrous scarring is markedly reduced.Conclusion We found that in-house fabricated A-PCL with WJ-MSC augmented skin repair with near-normal regeneration of skin appendages and reduced fibrosis.Lay SummaryStem cell use for wound healing and improved scar appearance is the next step in burns care. This study looked at the effects on wound healing and scar formation of Wharton’s jelly mesenchymal stem cells seeded on a scaffold created from aloe vera mixed with polycaprolactone and compared it to the same cells seeded on a bovine collagen sheet. A rat burn model was used. We found that mesenchymal stem cell seeded on the aloe vera scaffold accelerated wound healing and also regeneration of sweat gland and hair follicles compared to the other applications. This study supports the synergistic properties of aloe vera and WJ-MSCs in wound healing.
... 19,20 Clinical research on aloe sterol focused around skin health. 20,21 One in vitro study in human fibroblasts treated with aloe sterols showed increased collagen production compared with control. 21 The type of collagen produced was not specified; however, it was reported that expression of two key enzymes, COL1A1 and COL3A1, which are responsible for collagen production, was increased. ...
... 20,21 One in vitro study in human fibroblasts treated with aloe sterols showed increased collagen production compared with control. 21 The type of collagen produced was not specified; however, it was reported that expression of two key enzymes, COL1A1 and COL3A1, which are responsible for collagen production, was increased. In the same study, a double-blind placebo-controlled trial consisted of 56 women with dry skin who were supplemented with five tablets of aloe vera gel powder per day for 8 weeks (dosage not disclosed). ...
Research
Full-text available
Orally administered collagen in its many different forms is recognised as a highly biocompatible, safe form of supplementation, which has the potential to act on the body as an anti-inflammatory and antioxidant, and through structural remodelling and reduced lipotoxicity. The aim of this systematic review was to determine diseases where collagen has been indicated; assess safety, bioavailability and efficacy; and to provide therapeutic recommendations. It was concluded that collagen supplementation is strongly indicated for its positive therapeutic effect on pain management of osteoarthritis, balancing blood sugars in type II diabetes, wound healing, skin ageing, and post-exercise body composition and strength. Promising results were also seen for the use of collagen supplementation in osteoporosis, hypertension, rheumatoid arthritis, tendinopathy, cellulite, atopic dermatitis, sarcopenia and brittle nail syndrome. Although therapeutic recommendations were indicated in most of these diseases, owing in the large part to the use of these supplements as part of dual therapy or the uncertainty over translatability of branded products it was concluded that more studies are required to make definitive recommendations. There was a lack of clinical evidence to support the use of collagen for weight loss in obesity, gut health and in fibromyalgia.
... These receptors play roles as transcription factors in regulating the expression of genes involved in carbohydrate and lipid metabolism (Chinetti et al. 2000;Bragt and Popeijus 2008). Sterols in A. vera have also been shown to stimulate collagen and hyaluronic acid production by skin fibroblasts and, consequently, improve skin health in humans (Tanaka et al. 2015;Tanaka et al. 2016). ...
Article
Full-text available
Diabetes mellitus is defined as prolonged hyperglycemia, which can harm the eyes, kidneys, and cardiovascular and neurological systems. Herbal agents and their derived supplements have been used for treatment of diabetes mellitus as a part of integrated complementary medicine for centuries. Numerous studies have considered Aloe vera (L.) Burm.f, Xanthorrhoeaceae, as an alternative medicine due to its abundant bioactive chemicals, such as alkaloids, anthraquinones, and enthrones, with therapeutical properties including antioxidant, anti-inflammatory, neuro-protective, and anti-diabetic effects. Aloe vera has received considerable attention in traditional medicine for the treatment of several diseases including diabetes mellitus. Numerous studies have investigated the effects of herbal agents on diabetes mellitus using a streptozotocin-induced diabetic model. Thereby, this article reviews the effects of Aloe vera prescription on streptozotocin-induced diabetes mellitus to provide a clear insight into the role of this medicinal plant in several biological functions, such as antioxidant, wound healing, anti-inflammatory, anti-hyperglycemic, and anti-hyperlipidemic in diabetic models. Graphical abstract
... Известен заживляющий эффект препаратов на основе алоэ вера. Показано, что пероральный прием препарата алоэ вера (Aloe sterols) стимулирует синтез коллагена и гиалуроновой кислоты дермальными фибробластами [34]. ...
Article
Full-text available
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited disease developing due to genetic abnormalities in the synthesis of Type VII collagen by fibroblasts. A low production rate of Type VII collagen and abnormalities related to the formation of anchoring fibrils weaken the epidermis and derma adhesion strength, which results in the formation of blisters or erosions in case of any mechanical injury. Fibroblasts and keratinocytes belong to the key sources of Type VII collagen in the skin. Application of allogeneic fibroblasts is a promising cell technique for treating RDEB patients. The therapeutic effect of fibroblasts intradermal administration is stipulated by high stability of newly synthesized Type VII collagen and its ability to form anchoring fibrils in the area of the dermoepidermal junction. According to experimental and clinical studies, it is possible to boost the content of Type VII collagen in the dermoepidermal junction area and heal long-term skin defects in RDEB patients by means of intradermal administration of allogeneic fibroblasts.
... Une première étude randomisée, en double aveugle et contre placebo portant sur 58 femmes âgées de 20 à 50 ans, a montré qu'une supplémentation de 40 g/j pendant huit semaines augmenterait légèrement l'hydratation de la peau, diminuerait l'intensité des rides (-10 ± 5 % de largeur et -2,4 ± 0,3 % de profondeur en moins) par rapport au groupe placebo et stimulerait la production de collagène et d'acide hyaluronique par les fibroblastes (test sur des cultures cellulaires de fibroblastes dont la production de collagène et d'acide hyaluronique a respectivement doublé et triplé par rapport au groupe contrôle) [48] . ...
Article
Les compléments alimentaires représentent aujourd'hui un sujet de recherche important dans de nombreux domaines relatifs à la santé et la nutrition. L'utilisation de ces concentrés de vitamines, minéraux, ou autres substances à effets physiologiques ou nutritionnels, dans un but dermatocosmétique est également fréquente pour maintenir ou rétablir le bon état des parties superficielles du corps humain. Cet article s'adresse aux dermatologues et a pour objectif d'apporter une meilleure connaissance sur les relations entre compléments alimentaires et conditions non pathologiques liées à la peau, aux cheveux ou aux ongles. L'analyse de la littérature scientifique à ce sujet révèle une documentation relativement bien fournie concernant la peau alors que le domaine des phanères reste moins exploité. Un certain nombre d'ingrédients ont été associés à des effets intéressants mais beaucoup demandent la réalisation d'études cliniques plus robustes. © 2020 Elsevier Masson SAS. Tous droits réservés.
Article
Full-text available
Nanoencapsulation with safe materials improves delivery, stability, and activity of bioactive components. We report a novel safe, and effective method for the development of encapsulated antimicrobial essential oils (EO) for topical creams and gels. The method developed features three aspects that, to our knowledge, had not been previously demonstrated: (1) use of novel liposomes (LPs) to encapsulate EOs, (2) use of the EOs to replace synthetic organic solvents that are potentially toxic and/or leave harmful residues, and (3) an encapsulation process at temperatures below the boiling point of water. The LPs were made from soy lecithin, phytosterol, and α-tocopherol (vitamin E) that were synthesized using the EOs as the solvent. The liposomes were converted to nanoliposomes (NLPs) through a series of sonication, homogenization, and extrusion steps. Transmission electron microscopy indicated that the NLPs alone and nanoliposome encapsulated EOs (NLP-EOs) were spherical in shape with sizes ranging between 50 and 115 nm diameter and with negative zeta potentials ranging from -34 to -43 mV. There was no significant heavy metal contamination [As, Pb, Cd, Hg] based on inductively coupled plasma (ICP) mass spectrometry MS analyses. Nearly complete EO encapsulation (95% encapsulation efficiency) was achieved and confirmed by GC/MS. Three of the NLP-EOs made of various essential oils were used to make topical formulations (cream and gel) which exhibited antimicrobial activities against Escherichia coli (Gram negative) and Bacillus subtilis (Gram positive) bacteria. The creams with NLP-EOs were as active against the two bacteria in the antimicrobial assays as the conventional antibiotic Kanamycin that was used as positive control.
Chapter
Nutraceutical means nutrient and pharmaceutical, also known as medicinal/designer/functional foods as well as phytochemicals. These are the supplements of nutritional value which include daily products like dietary products, genetically modified products, herbal products, bio-yoghurts, vitamins, and fortified cereals. These medicinal or nutraceutical foods are originated from plant sources (garlic, ginger, onion, turmeric), dietary fiber and enzymes like papain and bromelain, various hydrolyzed proteins, and phytonutrients. Traditional nutraceuticals include phytochemicals, probiotic bacteria, enzymes, chemical compounds, nutrients, and plants. Recent investigations have shown that these compounds have promising outcomes in different pathological problems like cancer, diabetes, cardiovascular diseases, and atherosclerosis. These situations involve various changes like redox state alteration, and to counteract this situation, most of the nutraceuticals possess potential toward antioxidant activity. Thus, they are observed as safe sources for promotion of health, mainly to prevent different life-threatening diseases like diabetes, infection, and renal and gastrointestinal disorders, and play a vital role in food and pharmaceutical industries in maintaining life quality, good health, and longevity. Health professionals and nutritionists should research and work together for the benefit of mankind. Further, allocation of nutraceuticals can be done on the basis of sources of food, their action mechanism, chemical nature, etc. Interest in nutraceuticals is growing rapidly due to the rapid advances in prevention of diseases and healthcare product costs and elderly people using regular food industrial products which allow the enlargement in medicinal premium food products which are marketed to health-conscious people. They offer a great scope, and it is required to execute clinical trials for supplying nutraceuticals which generate huge benefits to customers and service providing companies. Recent trends show that nutraceuticals offer promising results in healthcare sector and nutraceutical consumption is increasing in global market day by day. In the present chapter, much work has been devoted to focus on the recent trends in herbal nutraceuticals for the prevention of cardiovascular disease, cancer, diabetes, hypertension, and arthritis disease.KeywordsNutraceuticalsPhytochemicalsAntioxidantsAnticancerAntidiabeticCVDProbiotic
Article
Full-text available
Background: The dietary supplement industry offers many oral cosmetics that purportedly assist in skin moisturization often with unclear evidence supporting efficacy and safety. To update the accessible proofs pertaining to the safety and effectiveness of oral dietary supplements to facilitate skin moisturizing via an all-around review and meta-analysis. Methods: Three on-line databases [Pubmed, Embase, and Cochrane Library (CENTRAL)] were retrieved from January 2000 to November 2021. An overall 66 randomized controlled trials (RCTs) of skin care were recognized. Meta-analysis was performed for dietary supplements with four or more available research. Results: Oral collagen or ceramide resulted in a statistically significant increase in skin hydration and a decrease in transepidermal water loss (TEWL) compared to placebo. No benefits regarding the improvement of skin conditions in terms of water content and TEWL were observed for lactic acid bacteria or Lactobacillus fermented foods. A statistically significant and positive effect on skin hydration was observed for both hyaluronan and procyanidin, with an unknown effect on TEWL due to insufficient RCTs. There was a non-significant improvement in the water content of stratum corneum for astaxanthin based on subgroup analyses. Among the dietary supplements trialed in ≤ 3 RCTs, the judgment regarding their effects on skin moisturizing was prevented by inconsistent conclusions as well as insufficient research. All food supplements were safe throughout the research (normally ≤ 24 weeks). Conclusion: Oral dietary supplements, including collagen, ceramides, hyaluronan, and procyanidin, were proven to be effective for skin moisturization. At present, for skin moisturization, the proofs supporting the recommendation of other dietary supplements, such as lactic acid bacteria and astaxanthin, are insufficient. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021290818.
Article
Full-text available
A method to quantitate five minor phytosterols named Aloe sterols identified from Aloe vera gel was validated using AVGP (Aloe vera gel powder) as the sample. To measure the Aloe sterols content, AVGP was extracted with chloroform/methanol (2:1, v/v) and analyzed by liquid chromatography-tandem mass spectrometry. The calibration curve revealed a high coefficient of determination (>0.999). The limit of quantification was 2.3-4.1 ng/mL. Average recoveries ranged from 95 to 105%. The intra-day and inter-day precision were 2.6-6.4% and 3.8-7.3%, respectively, confirming good method precision. Aloe sterols were also quantified in AVGE (Aloe vera gel extract) using this method. We showed that the composition ratio of each Aloe sterol in AVGP did not change in AVGE. Additionally, we measured the concentration of Aloe sterols in the capsule containing AVGE, and confirmed that it was stable even after 1 year of storage. In conclusion, a quantification method was established to simultaneously measure multiple plant sterols with similar structures. ・A quantification method to simultaneously measure several plant sterols with similar structures was established. ・Results from the intra-day precision and the inter-day precision confirmed good precision. ・This method can be applied to processed raw materials and/or foods in long-term storage.
Article
Riassunto Gli integratori alimentari rappresentano oggi un importante soggetto di ricerca in molti campi relativi alla salute e alla nutrizione. L’uso di questi concentrati di vitamine, minerali o altre sostanze con effetti fisiologici o nutrizionali è frequente anche per scopi dermatocosmetici, per mantenere o ripristinare il buono stato delle parti superficiali del corpo umano. Questo articolo è destinato ai dermatologi e si propone di fornire una migliore conoscenza della relazione tra integratori alimentari e condizioni non patologiche legate alla cute, ai capelli o alle unghie. L’analisi della letteratura scientifica su questo argomento rivela una documentazione relativamente ricca per quanto riguarda la cute, mentre il campo degli annessi resta meno esplorato. Un certo numero di ingredienti è stato associato a effetti interessanti, ma molti richiedono la realizzazione di studi clinici più robusti.
Article
Full-text available
Aloe vera gel supercritical CO2 extract (AVGE) has been shown to contain five phytosterols, reduce visceral fat accumulation, and influence the metabolism of glucose and lipids in animal model experiments. Recent epidemiologic studies have shown that obesity is an established risk factor for several cancers including colorectal cancer. Therefore, we examined the effects of AVGE on intestinal polyp formation in Apc-deficient Min mice fed a high-fat diet. Male Min mice were divided into normal diet (ND), high fat diet (HFD), low dose AVGE (HFD+LAVGE) and high dose AVGE (HFD+HAVGE) groups. The ND group received AIN-93G diet and the latter 3 groups were given modified high-fat AIN-93G diet (HFD) for 7 weeks. AVGE was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally to mice in HFD+LAVGE and HFD+HAVGE groups every day (except on Sunday) for 7 weeks at a dose of 3.75 and 12.5 mg/kg body weight, respectively. ND and HFD groups received 0.5% CMC alone. Between weeks 4 and 7, body weights in the HFD and HFD+LAVGE groups were reduced more than those in the ND group. However, body weights were not reduced in the HFD+HAVGE group. Mice were sacrificed at the end of the experiment and their intestines were scored for polyps. No significant differences were observed in either the incidence and multiplicity of intestinal polyps (≥0.5 mm in a diameter) among the three groups fed HFD. However, when intestinal polyps were categorized by their size into 0.5-1.4, 1.5-2.4, or ≥2.5 mm, the incidence and multiplicity of large polyps (≥2.5 mm) in the intestine in the HFD+HAVGE group were significantly lower than those in the HFD group. We measured plasma lipid (triglycerides and total cholesterol) and adipocytokine [interleukin-6 and high molecular weight (HMW) adiponectin] levels as possible indicators of mechanisms of inhibition. The results showed that HMW adiponectin levels in the HFD group were significantly lower than those in the ND group. However, the levels in the HFD+HAVGE group were significantly higher than those in the HFD group. These results indicate that HAVGE reduced large-sized intestinal polyps and ameliorated reduction in plasma HMW adiponectin levels in Min mice fed HFD.
Article
Full-text available
Adipose tissue is a hormonally active tissue that produces adipokines that influence the activity of other tissues. Adiponectin is an adipocyte-specific adipokine involved in systemic metabolism. We detected the expression of adiponectin receptors (AdipoR1 and AdipoR2) mRNA in cultured dermal fibroblasts. The full-length adiponectin (fAd), but not the globular adiponectin (gAd), increased hyaluronan (HA) production and upregulated HA synthase (HAS) 2 mRNA expression. AdipoR1 and AdipoR2 mRNAs were also expressed in keratinocytes, though neither fAd nor gAd had any effect on HA synthesis. In mouse skin, we found that adiponectin was present and decreased markedly with aging. The age-dependent pattern of adiponectin decrease in skin, correlated well with that of HA in skin. Our experiments were also the first to identify adiponectin production in cultured mouse sebocytes, a finding that suggests that skin adiponectin may derive not only from plasma and/or subcutaneous adipose tissue, but also from the sebaceous gland. These results indicated that adiponectin plays an important role in the HA metabolism of skin.
Article
We investigated the functions of adiponectin, an adipocyte-specific secretory protein and a new member of the family of soluble defense collagens, in hematopoiesis and immune responses. Adiponectin suppressed colony formation from colony-forming units (CFU)—granulocyte-macrophage, CFU-macrophage, and CFU-granulocyte, whereas it had no effect on that of burst-forming units—erythroid or mixed erythroid-myeloid CFU. In addition, adiponectin inhibited proliferation of 4 of 9 myeloid cell lines but did not suppress proliferation of erythroid or lymphoid cell lines except for one cell line. These results suggest that adiponectin predominantly inhibits proliferation of myelomonocytic lineage cells. At least one mechanism of the growth inhibition is induction of apoptosis because treatment of acute myelomonocytic leukemia lines with adiponectin induced the appearance of subdiploid peaks and oligonucleosomal DNA fragmentation. Aside from inhibiting growth of myelomonocytic progenitors, adiponectin suppressed mature macrophage functions. Treatment of cultured macrophages with adiponectin significantly inhibited their phagocytic activity and their lipopolysaccharide-induced production of tumor necrosis factor α. Suppression of phagocytosis by adiponectin is mediated by one of the complement C1q receptors, C1qRp, because this function was completely abrogated by the addition of an anti-C1qRp monoclonal antibody. These observations suggest that adiponectin is an important negative regulator in hematopoiesis and immune systems and raise the possibility that it may be involved in ending inflammatory responses through its inhibitory functions.
Article
Complementary and alternative medicine (CAM) represent a group of diverse medical and health care systems, practices, and products that are not considered to be part of conventional medicine. Biofeedback, acupuncture, herbal medication, massage, bioelectromagnetic therapy, meditation, and music therapy are examples of CAM treatments. Some dentists in the United States have used some of these treatments and products in their practices. Complementary medicines include herbal remedies, homeopathic medicines, and essential oils. There has been an increase in the use of herbal medicines in the US over the last 15-20 years. There is a public belief that these medicines are safe because they are made from natural sources. However, some of these products have associated adverse effects including toxicity and drug interactions. The health history taken by the dentist should include questions regarding the taking of herbal and over-the-counter medications. The dentist needs to be informed regarding the herbal and over-the-counter products that may impact the delivery of safe and effective dental treatment. In addition, the use of CAM treatments in dentistry should be based on evidence of effectiveness and safety as demonstrated in randomized clinical trials.
Article
Lophenol (Lo) and cycloartanol (Cy), minor phytosterols of Aloe vera gel, were previously identified as anti-diabetic compounds, and these compounds also reduced body fat in a type 2 diabetic model animal. In this study, we investigated the effects of Lo and Cy on peroxisome proliferator activated receptors (PPAR) using a luciferase reporter assay. DNA microarray and real-time quantitative RT-PCR (qPCR) analyses were also performed in a diet-induced obesity (DIO) mouse model. The Aloe phytosterols activated PPAR in a dose-dependent manner. The expression levels of many PPAR target genes were changed in the Aloe phytosterol group compared with those in the control high-fat diet (HFD) group. In particular, the expression levels of Fatp1, Acox1, Cpt1, and Hmgcs2 were significantly increased in the Aloe phytosterol group compared with those in the control HFD group; however, the expression level of ApoCIII was significantly decreased in the Aloe phytosterol group. We confirmed that Aloe phytosterols activate PPAR transcription in vitro. In addition, quantitative gene expression analysis in DIO mice suggested that Aloe phytosterols improve fatty acid metabolism in the liver.
Article
We examined the effects of lophenol (Lo) and cycloartanol (Cy), minor phytosterols of Aloe vera gel, in obese animal model of type II diabetes, Zucker diabetic fatty (ZDF) rats. Male ZDF rats were administered Lo and Cy at 25 μg/(kg day) daily for 44 days. Consecutive treatment of phytosterols suppressed the hyperglycemia, and random blood glucose levels after 35 days of treatment were 39.6 and 37.2% lower than the control, in Lo and Cy treatment groups, respectively. Consistent with the random blood glucose level, hemoglobin A1c (HbA1c) values of phytosterols treated rats were also lower than the control (Lo: 5.5 ± 0.8, Cy: 4.6 ± 0.7 vs. control: 7.2 ± 1.5). In the oral glucose tolerance test (OGTT) after 28 days of administration, the glucose intolerance was improved in phytosterols treatment groups. Additionally, the continuous administration of Lo and Cy also reduced the serum free fatty acid (FFA) and triglyceride (TG) levels except total cholesterol (T-Cho). Furthermore, the weights of total abdominal fat tissues were significantly lower than the control in ZDF rats with Lo (27.7%) and Cy (26.3%) treatment. These observations suggest that Aloe vera-derived phytosterols could reduce visceral fat accumulation, and would be useful for the improvement of hyperlipidemia and hyperglycemia.
Article
The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.
Article
Although adipocytokines affect the functions of skin, little information is available on the effect of adiponectin on the skin. In this study, we investigated the effect of adiponectin on hyaluronan synthesis and its regulatory mechanisms in human dermal fibroblasts. Adiponectin promoted hyaluronan synthesis along with an increase in the mRNA levels of hyaluronan synthase 2 (HAS2), which plays a primary role in hyaluronan synthesis. Adiponectin also increased the phosphorylation of AMP-activated protein kinase (AMPK). A pharmacological activator of AMPK, 5-aminoimidazole-4-carboxamide-1β-ribofuranoside (AICAR), increased mRNA levels of peroxisome proliferator-activated receptor-α (PPARα), which enhances the expression of HAS2 mRNA. In addition, AICAR increased the mRNA levels of HAS2. Adiponectin-induced HAS2 mRNA expression was blocked by GW6471, a PPARα antagonist, in a concentration-dependent manner. These results show that adiponectin promotes hyaluronan synthesis along with increases in HAS2 transcripts through an AMPK/PPARα-dependent pathway in human dermal fibroblasts. Thus, our study suggests that adiponectin may be beneficial for retaining moisture in the skin, anti-inflammatory activity, and the treatment of a variety of cutaneous diseases.
Article
The positive influence of Aloe vera, a tropical cactus, on the healing of full-thickness wounds in diabetic rats is reported. Full-thickness excision/incision wounds were created on the back of rats, and treated either by topical application on the wound surface or by oral administration of the Aloe vera gel to the rat. Wound granulation tissues were removed on various days and the collagen, hexosamine, total protein and DNA contents were determined, in addition to the rates of wound contraction and period of epithelialization. Measurements of tensile strength were made on treated/untreated incision wounds. The results indicated that Aloe vera treatment of wounds in diabetic rats may enhance the process of wound healing by influencing phases such as inflammation, fibroplasia, collagen synthesis and maturation, and wound contraction. These effects may be due to the reported hypoglycemic effects of the aloe gel.
Article
The capacity of fibroblasts to produce and organize the extracellular matrix and to communicate with other cells makes them a central component of tissue biology. Even so, fibroblasts remain a somewhat enigmatic population. Our inability to fully comprehend these cells is in large part due to the paucity of unique cellular markers and to their pervasive diversity. Much of our understanding of fibroblast diversity has evolved from studies where subpopulations of these cells have been produced without resorting to cell surface markers. In this regard, cloning and mechanical separation of tissues prior to establishing cultures has provided multiple subpopulations. Nonetheless, in isolated situations, the expression or lack of expression of Thy-1/CD90 has been used to separate fibroblast subsets. The role of fibroblasts in intercellular communication is emerging through the implementation of organotypic studies in which three-dimensional fibroblast culture are combined with other populations of cells. Such studies have revealed critical paracrine loops that are essential for organ development and for wound repair. These studies also provide a backdrop for the emerging field of tissue engineering. The participation of fibroblasts in the regulation of tissue homeostasis and their contribution to the aging process are emerging issues that require better understanding. In short, fibroblasts represent a multifaceted, complex group of cells.