Dietary Aloe Vera Supplementation Improves Facial Wrinkles and Elasticity and It Increases the Type I Procollagen Gene Expression in Human Skin in vivo

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DOI: 10.5021/ad.2009.21.1.6 · Source: PubMed
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No studies have yet been undertaken to determine the effect of aloe gel on the clinical signs and biochemical changes of aging skin. We wanted to determine whether dietary aloe vera gel has anti-aging properties on the skin. Thirty healthy female subjects over the age of 45 were recruited and they received 2 different doses (low-dose: 1,200 mg/d, high-dose: 3,600 mg/d) of aloe vera gel supplementation for 90 days. Their baseline status was used as a control. At baseline and at completion of the study, facial wrinkles were measured using a skin replica, and facial elasticity was measured by an in vivo suction skin elasticity meter. Skin samples were taken before and after aloe intake to compare the type I procollagen and matrix metalloproteinase 1 (MMP-1) mRNA levels by performing real-time RT-PCR. After aloe gel intake, the facial wrinkles improved significantly (p<0.05) in both groups, and facial elasticity improved in the lower-dose group. In the photoprotected skin, the type I procollagen mRNA levels were increased in both groups, albeit without significance; the MMP-1 mRNA levels were significantly decreased in the higher-dose group. Type I procollagen immunostaining was substantially increased throughout the dermis in both groups. Aloe gel significantly improves wrinkles and elasticity in photoaged human skin, with an increase in collagen production in the photoprotected skin and a decrease in the collagen-degrading MMP-1 gene expression. However, no dose-response relationship was found between the low-dose and high-dose groups.
6Ann Dermatol (Seoul)
Received April 21, 2008, Accepted for publication July 20, 2008
*A grant by Korea Food and Drug Administration (20042005).
Reprint request to: Jin Ho Chung, M.D., Department of Dermatology,
Seoul National University Hospital, 28, Yeongeon-dong, Jongno-gu,
Seoul 110-744, Korea. Tel: 82-2-2072-2414, Fax: 82-2-742-7344, E-mail:
Ann Dermatol (Seoul) Vol. 21, No. 1, 2009
Dietary Aloe Vera Supplementation Improves Facial
Wrinkles and Elasticity and It Increases the Type I
Procollagen Gene Expression in Human Skin in vivo
Soyun Cho, M.D., Ph.D.1,2,4, Serah Lee, M.S.3,4, Min-Jung Lee, M.S.3,4, Dong Hun Lee, M.D.2,
Chong-Hyun Won, M.D., Ph.D.1,4, Sang Min Kim, Ph.D.3,4, Jin Ho Chung, M.D., Ph.D.2,3,4
Department of Dermatology, 1Seoul National University Boramae Hospital, 2Seoul National University College of Medicine, 3Laboratory
of Cutaneous Aging Research, Clinical Research Institute, Seoul National University Hospital, 4Institute of Dermatological Science,
Medical Research Center, Seoul National University, Seoul, Korea
Background: No studies have yet been undertaken to
determine the effect of aloe gel on the clinical signs and
biochemical changes of aging skin. Objective: We wanted to
determine whether dietary aloe vera gel has anti-aging
properties on the skin. Methods: Thirty healthy female
subjects over the age of 45 were recruited and they received
2 different doses (low-dose: 1,200 mg/d, high-dose: 3,600
mg/d) of aloe vera gel supplementation for 90 days. Their
baseline status was used as a control. At baseline and at
completion of the study, facial wrinkles were measured
using a skin replica, and facial elasticity was measured by an
in vivo suction skin elasticity meter. Skin samples were taken
before and after aloe intake to compare the type I procollagen
and matrix metalloproteinase 1 (MMP-1) mRNA levels by
performing real-time RT-PCR. Results: After aloe gel intake,
the facial wrinkles improved significantly (p0.05) in both
groups, and facial elasticity improved in the lower-dose
group. In the photoprotected skin, the type I procollagen
mRNA levels were increased in both groups, albeit without
significance; the MMP-1 mRNA levels were significantly
decreased in the higher-dose group. Type I procollagen
immunostaining was substantially increased throughout the
dermis in both groups. Conclusion: Aloe gel significantly
improves wrinkles and elasticity in photoaged human skin,
with an increase in collagen production in the photopro-
tected skin and a decrease in the collagen- degrading MMP-1
gene expression. However, no dose- response relationship
was found between the low-dose and high-dose groups.
(Ann Dermatol (Seoul) 21(1) 611, 2009)
Aging, Aloe vera, Matrix metalloproteinase, Procollagen,
Skin aging is attributed to intrinsic (chronological) aging
and photoaging (extrinsic aging). Photoaging and intrinsic
aging are induced by damage to human skin by repeated
exposure to ultraviolet (UV) irradiation and the damage
due to the passage of time, respectively. An alteration in
collagen, which is the major structural component of skin,
has been considered to be a cause of skin aging in
naturally aged and photoaged skin. With increasing age,
there is a sustained reduction of collagen and an elevated
secretion of matrix-degrading enzymes called matrix
metalloproteinases (MMP) in old skin as compared with
young skin1. UV causes photoaging by generating reactive
oxygen species, and this subsequently triggers a cascade
of signaling mechanisms and this eventually causes a
decrease of collagen, and an increase of MMP, inflam-
mation, epidermal DNA damage and apoptosis. During
this process, activator protein 1 (AP-1) is activated by UV
irradiation and so AP-1-driven MMPs such as MMP-1 and
MMP-9 are induced. The UV-induced MMPs can degrade
collagen, which results in a collagen deficiency in pho-
todamaged skin and eventually skin wrinkling2.
Aloe Supplementation for Aging Skin
Vol. 21, No. 1, 2009 7
The discovery or development of a novel agent that can
delay the appearance of wrinkles and other features of
cutaneous aging has been the quest of the pharmaceutical
and cosmeceutical industries. Aloe barbadensis is com-
mercially known as aloe vera, and it is a substance for
which claims have been made about its anti-inflammatory,
healing, moisturizing, antibacterial, antifungal and anti-
viral properties3-5. The gel is obtained from the pulp of
aloe vera, a tropical cactus that belongs to the lily family,
and aloe has been used as folk remedy since Roman times
and it is now a familiar ingredient in a wide range of
healthcare and cosmetic products. The gel comprises the
inner, colorless part of the aloe vera leaf, and the exudate
from the outer layers is also used for therapeutic purposes.
Different gel constituents, including salicylates4, mag-
nesium lactate3, bradykinin or thromboxane6, and poly-
saccharides7,8 have been presented as the reasons for aloe
gel's efficacy. However, the biochemical basis for its
action or influence on tissue repair is just beginning to be
The reports concerned with the wound-healing effect of
aloe in experimental animals or humans have been
contradictory. In one such study, the incision wounds in
rats were rapidly healed by aloe gel and the effect was
attributed to more rapid maturation of collagen5. Other
researchers have suggested that aloe increases the oxygen
access of tissues as a result of an increased blood supply9
and others have suggested that aloe stimulates fibroblast
activity and collagen proliferation10. Mannose-6-phosphate
was identified as a cause of significant wound healing by
aloe11, and the healing by aloe was found to be accom-
panied by higher levels of hyaluronic acid and dermatan
sulfate, which were suggested to stimulate collagen
synthesis and fibroblast activity12. On the other hand,
controlled clinical trials in humans demonstrated no
benefit when aloe vera was incorporated into topical
therapy13, and one study demonstrated delayed wound
healing when aloe vera was incorporated14. Many of the
inconsistent clinical results obtained for the therapeutic
efficacy of aloe gel might have been caused by the history
of the sample after removal from the leaf, or even the
growing conditions of the plant15. No studies have yet
been undertaken to determine the effect of aloe gel on the
clinical signs and biochemical changes of cutaneous aging
and photoaging.
In this study, we investigated whether dietary aloe vera gel
supplementation affects facial wrinkles, elasticity and the
mRNA levels of type I procollagen and MMP-1 in human
skin in vivo, and we used a skin surface analyzing system
and biochemical methods to determine this.
A total of 30 healthy female subjects over the age of 45
and who passed a screening exam were randomized to
receive a low dose or a high dose of aloe. The exclusion
criteria included topical corticosteroid or retinoid use 2
weeks prior to study entry and use of systemic steroid,
vitamins or phototherapy 1 month prior to the study. The
subjects were not allowed to use anti-wrinkle/whitening
cosmetics, topical retinoids or chemical peels, or to take
any other functional food or vitamins during the study.
They were allowed to use sunscreen lotion with a Sun
Protection Factor of 30 or higher.
Aloe vera gel intake
The aloe vera gel liquid we used (manufacturer: Univera
Company, Seoul, Korea) is obtained by dissolving con-
centrated aloe vera gel powder in distilled water with
flavors. Two different concentrations of liquid were made
from the aloe vera gel powder (lower-dose: 1%, higher-
dose: 3%). The lower-dose group received 120 ml of 1%
aloe vera liquid, which is equivalent to 1,200 mg of aloe
vera gel/day; the higher-dose group received 120 ml of
3% aloe vera liquid, which translates to 3,600 mg of aloe
vera gel/day.
A complete blood count (CBC), liver function tests (LFT)
and urinalyses were conducted at baseline and at 90 days
after beginning the study. The subjects were instructed to
report any cutaneous or systemic adverse events after the
initiation of the study. For the subjects who agreed to
biopsies, skin samples were taken from the buttock skin
before and after aloe intake. The specimens for RT-PCR
analysis were snap-frozen in liquid nitrogen, and the
specimens for immunohistochemical staining were oriented
immediately in a cryomatrix (Shandon, Pittsburgh, PA,
USA) and then this was stored at 70oC.
This study was conducted according to the principles of
the Declaration of Helsinki. This study was approved by
the Institutional Review Board at Seoul National Uni-
versity Hospital, and all the subjects gave their written
informed consent.
Wrinkle and elasticity measurements
At baseline and after 90 days, facial wrinkles were mea-
sured in the crow's feet area using a skin replica and a
Visiometer SV 600 (CourageKhazaka Electronic, Köln,
Germany). The Visiometer is a computerized instrument
that makes a skin microrelief map from the replica using a
light transmission method. It has 5 roughness parameters:
depth of roughness (R1), mean depth of roughness (R2),
SY Cho, et al
8Ann Dermatol (Seoul)
maximum roughness (R3), depth of smoothness (R4) and
arithmetic average roughness (R5).
Facial elasticity was measured with a non-invasive, in vivo
suction skin elasticity meter Cutometer MPA 580 (Courage
Khazaka Electronic, Köln, Germany). The Cutometer
takes measurements based on the principle of suction
elongation, using an optical measuring unit. Of the mea-
sured and calculated R-parameters taken with the Cuto-
meter, certain ratios of the parameters are biologically
meaningful and these do not depend on skin thickness,
and so they can be compared between different skin sites
and subjects. In particular, R2 (gross elasticity), R5 (net
elasticity) and R7 (elasticity/complete curve) are known to
be indicators of skin elasticity, and the closer each value is
to 1, the more elastic the skin is.
All the measurements were performed in a controlled
environment room, with a constant room temperature
between 20 and 25oC and the humidity was between 45
and 55%, at the Clinical Research Institute, Seoul National
University Hospital.
Quantitative real-time RT-PCR
The total RNA was extracted from tissues using TRIZOL
reagent (Invitrogen Life Technologies, Carlsbad, CA, USA),
and 1μg of the total RNA was converted to cDNA using a
First Strand cDNA Synthesis Kit (Roche Applied Science,
Indianapolis, IN, USA). Quantitation of the procollagen α1
(I), the MMP-1 cDNA and the endogeneous reference
GAPDH cDNA was performed using a fluorescence de-
tection method (ABI PRISM 7000 Sequence Detection
System, Perkin Elmer Applied Biosystems, Foster City, CA,
USA). The sequence-specific PCR primer sets and a
TaqMan MGB probe (FAMTM dye-labeled) were purchased
from Applied Biosystems. The cycling conditions were
50oC for 2 min, 95oC for 10 min, followed by 40 cycles at
95oC for 15 sec and 60oC for 1 min. To quantify the
relative changes in the gene expression between each
sample, we used the comparative CT method, as was
previously described16. In the comparative CT method, the
ΔCT mean value obtained in the control sample is 0 and
the fold difference is 1.
Immunohistochemical staining
The samples were sectioned 4μm thick and fixed in
acetone (5 min at 20oC). The sections were blocked
with blocking solution (85-9043, Zymed, San Francisco,
CA, USA) for 30 min and then they were incubated in a
humidified chamber at 4oC for 18 hours with monoclonal
anti-human PIP antibody, which detects procollagen type I
C-terminal peptide (M011, 11,000, Takara, Shiga, Japan).
After washing in PBS, the sections were incubated with
biotinylated secondary antibody (85-9043, Zymed) for 15
min. The sections were incubated with streptavidin
(85-9043, Zymed) for 15 min, and the color reaction was
performed with AEC (3-amino-9-ethylcarbazole; 00-2007,
Zymed) developing solution for 5 to 10 min. The cell
nuclei were then counterstained with Mayer's hema-
toxylin (S3309, Dako), and the samples were mounted
using Faramount Aqueous Mounting Medium (S3025,
Dako, USA).
Statistical analysis
The significance of differences between the higher and
lower dose groups was analyzed by using the Mann-
Whitney U-test for comparison of the baseline values
between the two groups; Wilcoxon's signed rank test was
used for comparison of the before- and after-aloe vera gel
intake values in each group. For all the tests, a p value
0.05 was considered significant.
All 30 subjects completed the trial without any adverse
events. The ages of the 30 subjects ranged from 49 to 74
years (average age: 56.2 yrs), and their body weights
ranged from 47 to 75 kg (average weight: 58.8 kg). In the
lower-dose group (n=15), the average age was 57.8±7.1
years and the average weight was 55.9±5.8 kg; in the
higher-dose group (n=15), the average age was 54.5±6.3
years and the average weight was 61.8±8.8 kg. By the
Mann-Whitney test, there was no significant difference in
the ages and body weights between the 2 groups, and so
the selection of subjects was deemed appropriate. No
subjective adverse events were reported. The laboratory
evaluations revealed no significant abnormalities in the
CBC, the LFTs and the urinalysis.
Aloe improves facial wrinkles and elasticity in pho-
toaged human skin in vivo
Comparison of the facial wrinkles before and after aloe gel
intake, as measured by the skin replica and the Visio-
meter, is shown in Table 1. The Visiometer R values R1
thru R5 decrease as the wrinkles diminish, that is, the skin
surface roughness decreases. Hence, the facial wrinkles in
both groups were shown to have significantly decreased
after 3 months of aloe vera supplementation, with the
Visiometer R1 thru R4 values being decreased (p0.05,
Wilcoxon's signed rank test) in the lower-dose group, and
the R1, R3-R5 values were significantly decreased in the
higher-dose group.
The Cutometer was used to measure changes in skin
elasticity. The closer the value is to 1, the more elastic the
Aloe Supplementation for Aging Skin
Vol. 21, No. 1, 2009 9
Table 2. Changes in the skin elasticity as measured by the Cuto
meter in each treatment group
Group R
values* Baseline
After aloe vera
gel intake
(90 days)
*The closer the value is to 1, the more elastic the skin is.
Fig. 1. The type I procollagen mRNA levels measured by real-time RT-PCR before and after aloe vera gel intake in the lower-dose
group (n=6) and the higher-dose group (n=6). Wilcoxon’s signed rank test was used for statistical analysis.
Fig. 2. The collagen-degrading MMP-1 mRNA levels before and after aloe vera gel intake in the lower-dose group (n=6) and the
higher-dose group (n=6). Statistical significance was tested by Wilcoxon’s signed rank test.
Table 1. Changes in facial wrinkles as measured by the Visio-
meter in each treatment group
Group R
values* Baseline
After aloe vera
gel intake
(90 days)
*Visiometer R values R1 thru R5 decrease as the wrinkles
skin is. After 90 days of aloe vera supplementation, the R5
and R7 values were increased significantly in the lower-
dose group (Table 2), indicating increased cutaneous
elasticity. In the higher-dose group, the Cutometer R
values all increased, but this was without statistical
Aloe increases the type I procollagen gene expression
in photoprotected human skin in vivo
The type I procollagen and collagen-degrading MMP-1
SY Cho, et al
10 Ann Dermatol (Seoul)
Fig. 3. Type I procollagen (Takara) immunostaining in the buttoc
skin before and after aloe vera intake (original magnification
×200). The results are representative of 6 biopsied subjects in
each group.
gene expressions were compared by performing real-time
RT-PCR. In the lower-dose group (n=6), the type I pro-
collagen mRNA levels increased to 4.74±1.25 times the
baseline level (p0.05); in the higher-dose group (n=6),
these levels increased 1.75±0.41 fold (p0.05) (Fig. 1).
The MMP-1 mRNA levels were nearly unchanged in the
lower-dose group, with a 1.41±0.31 fold increase after
aloe intake (n=6); however, in the higher-dose group, the
MMP-1 mRNA transcripts were significantly (p0.05, n=
6) decreased to 0.51±0.13 times the baseline level (Fig. 2).
Type I procollagen immunostaining with anti-PIP antibody
demonstrated substantially increased intracellular and
extracellular procollagen expressions throughout the
dermis after aloe vera gel intake in both treatment groups
(Fig. 3).
This is the first clinical research to determine the effects of
dietary aloe supplementation on facial wrinkles/elasticity
and the type I procollagen and MMP-1 gene levels in aged
human skin. In this study, we found that aloe vera gel
supplementation clinically improved facial wrinkles and
elasticity, while it increased type I procollagen and it
decreased the MMP-1 gene expressions in the photo-
protected skin.
In this study, the degree of clinical wrinkles was ob-
jectively measured by using a device (the Visiometer) that
converts the skin surface roughness to numerical values.
The facial wrinkles decreased in both the lower-dose and
higher-dose groups; however, no dose-response relation-
ship was seen in this study. This may be partially
attributed to the small number of subjects in this study and
a relatively short time period of aloe gel supplementation.
The decrease in facial wrinkles as measured by the
Visiometer reflects increased type I procollagen in both
dosing groups. At the gene level, lower-dose aloe was
shown to increase type I procollagen mRNA in the
photo-protected buttock skin, albeit without statistical
significance, whereas no change was seen in the MMP-1
mRNA levels. In the higher-dose group, while aloe gel
had little effect on the type I procollagen mRNA levels, it
caused a significant decrease in the MMP-1 mRNA levels.
As a result, both dosing groups would have a net gain of
procollagen that would correlate clinically with the
improvement of wrinkles, as measured by the Visiometer.
Type I procollagen immunostaining also demonstrated an
upregulated protein expression in both groups.
The mechanism by which aloe exerts its anti-aging effects
is unknown. The therapeutic action of aloe has been
studied mostly for wound healing. When wounded
diabetic rats were treated orally and topically with aloe
gel, increased collagen formation was later demonstrated17,
and the collagen formed had a higher degree of cross-
linking, indicating enhanced levels of type III collagen18.
According to the literature on the therapeutic effect of
aloe, immunostimulation frequently appears as a con-
tributory factor. Aloe gel extracts, when applied after UV
exposure, were found to prevent suppression of local and
systemic immunity to haptens and delayed type hypersen-
sitivity responses to Candida albicans and alloantigens8,19.
This was attributed to the presence of polysaccharides in
the aloe vera gel. They have no significant anti-oxidant
activity; the immune-protective action of aloe polysac-
charides takes place at a step downstream from DNA
damage and repair, possibly by modulating the DNA-
damage-activated signal transduction pathways20. These
compounds may act by novel mechanisms to block the
signal transduction pathways and the production of
immunosuppressive cytokines. An acetylated glucoman-
nan in aloe was found to be the biologically active,
dominant polysaccharide, so much so that it was named
acemannan5. Acemannan from aloe was shown to
increase collagen biosynthesis, and perhaps this occurred
through macrophage stimulation21. In addition, active
glycoproteins have been demonstrated in aloe gel and
they may well play some part in aloe's therapeutic
activity, either immunologically as lectins or as proteases
such as anti-bradykinins. Superoxide dismutase activities
have also been reported from Aloe vera gel22.
There are 3 cases of oral aloe vera-induced hepatitis in the
medical literature23-25. In this study, no toxicity was
observed in association with oral aloe intake. The doses
used in the study were determined arbitrarily based on the
Aloe Supplementation for Aging Skin
Vol. 21, No. 1, 2009 11
daily recommended dosage of aloe by the manufacturer of
the study material. From the two doses used in this study,
no dose-response relationship could be demonstrated
clinically (wrinkles and the elasticity measures), biochemi-
cally (procollagen and the MMP-1 gene levels) or micro-
scopically (procollagen staining). Our results indicate no
added advantage of high-dose aloe vera gel ingestion for
cutaneous anti-aging purposes. The limitations of the
study include the lack of a control group. In addition,
daily sunblock use may have added to the protective
effects of aloe; however, sunblock alone does not actively
increase procollagen production or reduce the MMP-1
gene expression. It only renders skin less susceptible to
further photodamage that would occur with the passage of
time. Therefore, the role of sunblock as an active anti-
aging substance could be excluded. For determining the
optimal effective daily dosage of aloe, a placebo-con-
trolled study with a larger number of subjects and a longer
study period is warranted.
Since aloe significantly decreased wrinkles and it
increased elasticity in photoaged human skin in vivo with
an increase of the net procollagen, oral aloe gel sup-
plementation may be a novel anti-aging strategy that
prevents and repairs cutaneous photoaging. A future
challenge will be to determine the mechanism of action of
aloe gel in preventing cutaneous aging.
The authors are indebted to Ae-Kyong Woo and Joo-Mi
Shim for coordinating the study and procuring the cu-
taneous tissues. This research was supported by a grant
from the Korean Food and Drug Administration.
1. Varani J, Warner RL, Gharaee-Kermani M, Phan SH, Kang S,
Chung JH, et al. Vitamin A antagonizes decreased cell
growth and elevated collagen-degrading matrix metallopro-
teinases and stimulates collagen accumulation in naturally
aged human skin. J Invest Dermatol 2000;114:480-486.
2. Fisher GJ, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ.
Pathophysiology of premature skin aging induced by
ultraviolet light. N Engl J Med 1997;337:1419-1428.
3. Shelton RM. Aloe vera. Its chemical and therapeutic pro-
perties. Int J Dermatol 1991;30:679-683.
4. Klein AD, Penneys NS. Aloe vera. J Am Acad Dermatol
5. Reynolds T, Dweck AC. Aloe vera leaf gel: a review update.
J Ethnopharmacol 1999;68:3-37.
6. Natow AJ. Aloe vera, fiction or fact. Cutis 1986;37:106, 108.
7. Strickland FM, Darvill A, Albersheim P, Eberhard S, Pauly M,
Pelley RP. Inhibition of UV-induced immune suppression
and interleukin-10 production by plant oligosaccharides and
polysaccharides. Photochem Photobiol 1999;69:141-147.
8. Byeon SW, Pelley RP, Ullrich SE, Waller TA, Bucana CD,
Strickland FM. Aloe barbadensis extracts reduce the pro-
duction of interleukin-10 after exposure to ultraviolet radia-
tion. J Invest Dermatol 1998;110:811-817.
9. Davis RH, Rosenthal KY, Cesario LR, Rouw GA. Processed
Aloe vera administered topically inhibits inflammation. J Am
Podiatr Med Assoc 1989;79:395-397.
10. Thompson JE. Topical use of aloe vera derived allantoin gel
in otolaryngology. Ear Nose Throat J 1991;70:119.
11. Davis RH, Donato JJ, Hartman GM, Haas RC. Anti-inflam-
matory and wound healing activity of a growth substance in
Aloe vera. J Am Podiatr Med Assoc 1994;84:77-81.
12. Chithra P, Sajithlal GB, Chandrakasan G. Influence of Aloe
vera on the glycosaminoglycans in the matrix of healing
dermal wounds in rats. J Ethnopharmacol 1998;59:179-186.
13. Thomas DR, Goode PS, LaMaster K, Tennyson T.
Acemannan hydrogel dressing versus saline dressing for
pressure ulcers. A randomized, controlled trial. Adv Wound
Care 1998;11:273-276.
14. Schmidt JM, Greenspoon JS. Aloe vera dermal wound gel is
associated with a delay in wound healing. Obstet Gynecol
15. Yaron A. Characterization of Aloe vera gel before and after
autodegradation, and stabilization of the natural fresh gel.
Phytother Res 1993;7:S11-S13.
16. Livak KJ, Schmittgen TD. Analysis of relative gene
expression data using real-time quantitative PCR and the
2(-Delta Delta C(T)) Method. Methods 2001;25:402-408.
17. 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.
18. Chithra P, Sajithlal GB, Chandrakasan G. Influence of Aloe
vera on collagen characteristics in healing dermal wounds in
rats. Mol Cell Biochem 1998;181:71-76.
19. Strickland FM, Pelley RP, Kripke ML. Prevention of ultraviolet
radiation-induced suppression of contact and delayed
hypersensitivity by Aloe barbadensis gel extract. J Invest
Dermatol 1994;102:197-204.
20. Strickland FM. Immune regulation by polysaccharides: im-
plications for skin cancer. J Photochem Photobiol B
21. Lindblad WJ, Thul J. Sustained increase in collagen bio-
synthesis in acemannan impregnated PVA implants in the rat
[abstract]. Wound Repair Regen 1994;2:84.
22. Sabeh F, Wright T, Norton SJ. Isozymes of superoxide
dismutase from Aloe vera. Enzyme Protein 1996;49:212-
23. Rabe C, Musch A, Schirmacher P, Kruis W, Hoffmann R.
Acute hepatitis induced by an Aloe vera preparation: a case
report. World J Gastroenterol 2005;11:303-304.
24. Kanat O, Ozet A, Ataergin S. Aloe vera-induced acute toxic
hepatitis in a healthy young man. Eur J Intern Med
25. Bottenberg MM, Wall GC, Harvey RL, Habib S. Oral aloe
vera-induced hepatitis. Ann Pharmacother 2007;41:1740-
  • ... Oral supplementation with A. vera gel was reported in clinical trials to improve facial wrinkles and elasticity. 16 We also previously showed that human dermal fibroblasts produced 2-and 1.5-fold levels of collagen and hyaluronic acid after cultivation in the presence of Aloe sterol in vitro, respectively, and we observed a reduction of the facial wrinkle depth by 8 weeks of oral ingestion of 40 lg Aloe sterol in a human study. 17 Furthermore, we confirmed the presence of statistically significant differences in the levels of skin hydration, TEWL, skin elasticity and the dermal collagen score between 40 lg of the Aloe sterol-treated group and placebo group. ...
    ... A previous study analyzed the effect of A. vera gel intake on the buttock skin of Korean women using immunostaining and reverse transcription polymerase chain reaction, and found that A. vera increases the amount of type I procollagen. 16 Furthermore, Aloe sterol is reported to promote the synthesis of type I and III collagen in cultured human dermal fibroblasts. 17 Ingested Aloe sterol has been shown to reach the peripheral tissues through the bloodstream, so the collagen content of the dermis appears to be induced through the stimulation of fibroblasts by Aloe sterol. ...
    ... In the current study, the cut-off level of skin hydration for subgroup analysis was based on the results of our previous study using high-dose Aloe sterol, conducted from summer to winter. 16 Thus, basal hydration levels in participants of the previous study are expected to be different from those of the current study which was performed over winter and spring. Conversely, basal levels were similar in the two studies, approximately 24-25 AU in the Aloe sterol group and placebo group. ...
    Full-text available
    Daily oral intake of 40 μg Aloe sterol was shown in a double‐blind clinical trial to significantly increase skin barrier function, moisture and elasticity. Ultrasonographic results also suggested that the intake of Aloe sterol increases collagen content in the dermis. Here, we evaluate the effects of a much smaller dose of Aloe sterol, approximately half that used previously, on skin functions in more detail. This is a monocentric, double‐blind, randomized, placebo‐controlled, supplementation study of the effects of low‐dose Aloe sterol on skin transepidermal water loss, hydration, collagen score, evaluation of objective or subjective symptoms, and safety after 12 weeks of daily intake. We randomly administrated either Aloe sterol or placebo to 122 healthy volunteers. Transepidermal water loss was significantly reduced and collagen score was increased in the Aloe sterol group compared with the placebo group at week 12. In the Aloe sterol group, there was significant improvement of objective skin condition (face erythema and pruritus of inner and outer arms) at week 12 compared with week 0, but not in the placebo group. Subjectively, there was significant improvement of visual analog scale of skin acne, fingernail brittleness and constipation in the Aloe sterol group. According to subgroup analysis, although not planned before the study initiation, subjects with dry skin in the Aloe sterol group had significantly increased skin hydration values at week 12 compared with the placebo group. Our results confirmed that even low‐dose Aloe sterol ingestion improves skin moisture by promoting skin barrier function and dermal collagen production, which contributes to maintenance of healthy skin.
  • ... Collagen is a major structural component of human skin, responsible for skin elasticity and is synthesized from dermal fibroblast-derived procollagen [61]. Sustained reduction in collagen and increased matrix-degrading enzymes in naturally aged and photo-aged skin are considered causes of skin aging [69,70]. These increased matrix metalloproteinases (MMP) are the result of a signaling cascade triggered by ROS and it causes apoptosis, collagen reduction, inflammation and wrinkling. ...
    ... Both concentrations also increased cutaneous elasticity, but it was only statistically significant for the lower-dose group. Moreover, the Aloe supplementation increased gene expression of type I procollagen and the higher concentration supplementation decreased MMP-1 mRNA levels significantly [70]. Cho et al. proposed acemannan, a biologically active acetylated glucomannan in Aloe, to be one of the active components contributing to their results since it has been shown to increase biosynthesis of collagen. ...
    The skin is the largest organ and functions as a barrier to protect the underlying tissues against the elements and pathogens, while also fulfilling many physiological roles and biochemical functions such as preventing excessive water loss. Skin disorders vary greatly in terms of origin, severity, symptoms and affect persons of all ages. Many plants have been used for medicinal purposes since ancient times including the treatment of skin disorders and diseases. Aloe represents one of the earliest medicinal plant species mentioned in antique scriptures and even in rock art dating back thousands of years. Different Aloe species and materials have been used in the prevention and treatment of skin related disorders. Aloe vera is the most commonly used Aloe species for medicinal purposes. Some of the most prominent skin related applications and disorders that Aloe materials have been investigated for are discussed in this paper, which include cosmetic, radiation, cancer, wound and antimicrobial applications. Both in vitro and in vivo studies are included in the discussions of this paper and comprehensive summaries of all these studies are given in tables in each section. Although some contradictory results were obtained betweenamong studies, certain Aloe materials have shown excellent efficacy and exhibited potential for the treatment of skin related disorders and cosmetic applications.
  • ... Plant extracts have been used for cosmetics and skincare products since ancient times, as a complex mixture of natural compounds with different structures and functions. Reportedly, various plant extracts, such as fermented barley and soybean mixtures [22], horsetail (Equisetum arvense L.) [23], Aloe vera [24,25], pine bark (Pinus pinaster), Citrus paradisi and Rosmarinus officinalis extracts, redorange complex [26], and Polypodium leucotomos extract [27] are effective skincare agents in animal or clinical studies. Additionally, the fermented honeybush (Cyclopia intermedia) extract (HU-018) 400 mg or 800 mg, currently released as a health functional food, reduces skin wrinkles, improves skin elasticity, and enhances skin moisture [28]. ...
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    Previously, we reported that the hot water extract of Hydrangea serrata leaves (WHS) and its active component, hydrangenol, possess in vitro and in vivo effects on skin wrinkles and moisturization. We conducted a randomized, double-blind, placebo-controlled trial to clinically evaluate the effect of WHS on human skin. Participants (n = 151) were randomly assigned to receive either WHS 300 mg, WHS 600 mg, or placebo, once daily for 12 weeks. Skin wrinkle, hydration, elasticity, texture, and roughness parameters were assessed at baseline and after 4, 8, and 12 weeks. Compared to the placebo, skin wrinkles were significantly reduced in both WHS groups after 8 and 12 weeks. In both WHS groups, five parameters (R1–R5) of skin wrinkles significantly improved and skin hydration was significantly enhanced when compared to the placebo group after 12 weeks. Compared with the placebo, three parameters of skin elasticity, including overall elasticity (R2), net elasticity (R5), and ratio of elastic recovery to total deformation (R7), improved after 12 weeks of oral WHS (600 mg) administration. Changes in skin texture and roughness were significantly reduced in both WHS groups. No WHS-related adverse reactions were reported. Hence, WHS could be used as a health supplement for skin anti-aging.
  • ... Menurut (Soyun, et al., 2009) penuaan kulit ditandai oleh pigmentasi yang tidak teratur, peningkatan kerutan, kehilangan elastisitas, kulit menjadi kering dan kasar (Bisset, et al., 1990). ...
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    Penuaan secara alamiah terjadi pada makhluk hidup. Efek dari proses penuaan pada manusia adalah terjadinya gangguan secara fisik seperti kehilangan elastisitas kulit sehingga kulit menjadi keriput dan juga hiperpigmentasi. Sebagai upaya dalam mencegah maupun mengatasi hal tersebut adalah dengan menggunakan antioksidan. Antioksidan dapat menginhibisi terjadinya reaksi oksidasi sel sehingga dapat mengurangi kerusakan sel dan penuaan dini. Beberapa tumbuhan yang telah diteliti memiliki potensi sebagai antiaging adalah mahkota dewa, sirih, narwastu, rambutan, jagung, ubi jalar, kelor, raspberi, anggur dan lengkeng. Untuk memudahkan penggunaan tanaman tersebut sebagai antioksidan, bentuk sediaan kosmetik merupakan pilihan utama yang dapat digunakan secara mudah dan nyaman. Bentuk sediaan kosmetik dapat berupa sediaan gel, krim, bedak, salep dan losion. Review artikel ini akan memaparkan formulasi sediaan krim anti-aging yang mengandung zat aktif dari ekstrak tanaman. Review artikel ini menggunakan metode penelitian komparatif dengan mengumpulkan berbagi sumber pustaka primer dari 18 jurnal penelitian. Hasil review ini mengindikasikan bahwa semua krim yang diformulasikan stabil secara fisikokimia dengan tidak adanya tanda-tanda kerusakan bentuk sediaan emulsi dan perubahan sifat fisikokimia selama uji stabilitas dilaksanakan. Sehingga formula ini berpotensi digunakan dalam pengembangan formula sediaan krim yang mengandung zat aktif dari ekstrak tanaman. Kata kunci: Anti-aging, Sediaan Krim, Ekstrak
  • ... 11,12 Also, it was reported that Aloe vera increased the collagen content of the granulation tissue as well as its degree of cross linking as seen by increasing aldehyde content and decreased acid solubility. 13,14 According to previous studies on different impacts of both Plantago major and Aloe vera, some of which are supposed to influence the process of wound healing, it is assumed that a mixture of these two herbal medicines may provide a potent material in treatment of skin wounds. Thus, in this study, we aimed to determine the healing effects of this mixture on full-thickness skin wounds in rat models by using histomorphometrical and stereological parameters. ...
  • ... 11,12 Also, it was reported that Aloe vera increased the collagen content of the granulation tissue as well as its degree of cross linking as seen by increasing aldehyde content and decreased acid solubility. 13,14 According to previous studies on different impacts of both Plantago major and Aloe vera, some of which are supposed to influence the process of wound healing, it is assumed that a mixture of these two herbal medicines may provide a potent material in treatment of skin wounds. Thus, in this study, we aimed to determine the healing effects of this mixture on full-thickness skin wounds in rat models by using histomorphometrical and stereological parameters. ...
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    BACKGROUND Previous studies indicated that both Plantago major and Aloe vera have anti-inflammatory, tissue regeneration, antioxidant, and immune-stimulatory effects. It is assumed that a mixture of these two herbal medicines may provide a potent material in treatment of skin wound injuries. Therefore, in this study we investigated the effects of Plantago major and Aloe vera mixture in the process of wound healing in rat models according to stereological parameters. METHODS In an experiential study, 36 male Sprague-Dawley rats (200±20 g) were randomly assigned into three groups (n=12): The control group which received no treatment, gel base treated group, and the 5% Plantago major and 5% Aloe vera mixture gel treated group (PA group). Treatments were done every 24 hrs for 15 days. Wound closure rate, volume densities of the collagen bundles and the vessels, vessel’s length density and mean diameter, and fibroblast populations were estimated using stereological methods. RESULTS PA treated group showed faster wound closure rate in comparison with control and gel-base groups (p<0.05). Numerical density of fibroblasts, volume density of collagen bundles, mean diameter, and volume densities of the vessels in PA group were significantly higher than the control and the gel-base treated groups (p<0.05). CONCLUSION We showed that Plantago major and Aloe vera mixture has the ability to improve wound healing by enhancing fibroblast proliferation, collagen bundle synthesis and re-vascularization in skin injuries.
  • ... More compact and regular arrangement of the dermal collagen fibers was observed, both in comparison to the group of diabetic rats as well as the control healthy group. Bee venom as a cosmetic ingredient may be useful as a topical agent for promoting skin regeneration or as a treatment for certain epidermal conditions, as it has shown that when wounded mice were treated topically with bee venom, increased collagen protein synthesis was demonstrated, which might be related to increased proliferation and migration of human epidermal keratinocytes [23][24][25]. ...
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    Abstract: Background: diabetes is a chronic disease that causes serious dermatologic problems. Recently bee venom (BV) has been used as a traditional medicine to treat variety of conditions. This study was designed to assess the effects of BV on the structure of unwounded thick skin in type 1 diabetes in adult male albino rats. Materials and Methods: Thirty adult male albino rats were divided into four groups: control group, BV control group, diabetic group and BV treated group. In the diabetic group each rat received single IP injection of 45mg/kg streptozotocin (STZ) in 100 mM citrate buffer pH 4.5. In BV treated group, each rat received STZ as in diabetic group, then after conformation of diabetes, each rat received IP injection of 0.5 mg/kg BV twice weekly for four consecutive weeks. Blood samples were taken for monitoring blood glucose levels. At the end of the experiment, thick skin was obtained from the planter surface of hind limb from all rats. Samples were processed for H&E, Mallory`s trichrome stain and immunohistocehmical reaction for protein gene product 9.5 (PGP-9.5). Statistical and histomorphometric studies were also done. Results: A significant decrease in serum glucose level was noticed in rats treated with BV, compared to untreated diabetic rats. In diabetic group, H&E stained skin sections showed significant decrease in epidermal thickness with a significant increase in the number of atypical cells with deeply stained nuclei and perinuclear cytoplasmic vacuolation, compared to other groups. Mallory stained sections of diabetic group showed disorganized and less crowded collagen bundles in the reticular dermis. Immunohistocehmical reaction for PGP- 9.5in the same group illustrated decreased immune reaction for nerve fibers in the dermis of the skin. However, BV treated group showed preservation of skin structure. The epidermis appeared almost similar to the control group with the appearance of its usual five layers. Most of collagen fibers appeared with uniform diameter and showed compact and regular arrangement. Preserved cutaneous innervation was also detected. Conclusion: The current study shows that bee venom is effective in preventing skin changes accompanied with diabetes mellitus type I, as it preserves the structure and innervation of unwounded thick skin.
  • Article
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    The nutricosmetics are products and ingredients that act as nutritional supplements to care skin, nails, and hair natural beauty. They work from the inside to promote beauty from within. Nutricosmetic is the latest trend in the beauty industry. This tendency rapidly gained many followers because it fits with the modern culture: Today, consumers are very careful with the food that they introduce into their body, and there is also an increasing demand for natural products able to enhance one's health and beauty without side effects and significant traction before use. However, many nutricosmetic products are considered effective due to the historical use and word of mouth. Comprehensive analysis of the global nutricosmetics market is conducted considering form, end‐user applications, and some product components such as collagen, peptides, proteins, vitamins, carotenes, minerals, and omega‐3 fatty acid are reported. Plant extract ingredients used in nutricosmetic are also described.
  • Article
    Natural molecules are becoming more accepted choices as cosmetic agents, many products in the market today claim to include natural components. Plants include many substances that could be of a value in the whitening skin and working as anti-aging agents. A wide range of articles related to natural skin whitening and anti-aging agents have been reviewed. Many plant-derived and natural molecules have shown to affect melanin synthesis by different mechanisms, examples include Arbutin, Ramulus mori extract, Licorice extract, Glabridin, Liquiritin, Kojic acid, Methyl gentisate, Aloesin, Azelaic acid, Vitamin C, Thioctic acid, Soya bean extracts, Niacinamide, α and β-hydroxy acids, Lactic acid, Chamomile extract, and Ellagic acid. Some of the widely used natural anti-aging products as natural antioxidants, collagen, hyaluronic acid, and coenzyme Q can counteract the effects of reactive oxygen species in skin cells and have anti-aging properties on the skin. It was concluded that many natural products including antioxidants can prevent UV-induced skin damage and have whitening and anti-aging effects. It is very important to develop and stabilize appropriate methods for the evaluation of the whitening and anti-aging capacity of natural products and their exact mechanism of action to ensure real efficacy based on evidence-based studies. The attention should be oriented on the formulations and the development of an appropriate vehicle to ensure suitable absorption of these natural products in addition to evaluating the suitable concentration of these molecules required having the desired effects without causing harmful side effects.
  • Chapter
    An important component of proper skin function is the quality and quantity of macro‐ and micro‐nutrients ingested. Atopic dermatitis (AD) tends to begin in early life when the epithelial barrier surface is unable to retain moisture and protect the skin from bacteria, irritants, and allergens, leading to elevated immunoglobulin levels and allergic skin reactions. The lack of fermented foods in the diet, useful for maintaining gut health, appears to be a risk factor in AD development. Diet has been shown to have a correlation with skin aging. In general, antioxidants are effective in reducing the free radical damage of collagen and elastin and in preventing premature aging. Antioxidants provide photoprotection and are derived primarily through nutrition. Nutrients and food ingredients have been reported to play a role in the maintenance or alterations of gut microbiota and intestinal barrier function. Alcohol abuse in particular is prevalent in leaky gut.
  • Article
    The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-DeltaDeltaCr) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-DeltaDeltaCr) method. In addition, we present the derivation and applications of two variations of the 2(-DeltaDeltaCr) method that may be useful in the analysis of real-time, quantitative PCR data. (C) 2001 Elsevier science.
  • Article
    Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities. Photoaging is caused in part by damage to skin connective tissue by increased elaboration of collagen-degrading matrix metalloproteinases, and by reduced collagen synthesis. As matrix metalloproteinase levels are known to rise in fibroblasts as a function of age, and as oxidant stress is believed to underlie changes associated with both photoaging and natural aging, we determined whether natural skin aging, like photoaging, gives rise to increased matrix metalloproteinases and reduced collagen synthesis. In addition, we determined whether topical vitamin A (retinol) could stimulate new collagen deposition in sun-protected aged skin, as it does in photoaged skin. Sun-protected skin samples were obtained from 72 individuals in four age groups: 18-29 y, 30-59 y, 60-79 y, and 80+ y. Histologic and cellular markers of connective tissue abnormalities were significantly elevated in the 60-79 y and 80+ y groups, compared with the two younger age groups. Increased matrix metalloproteinase levels and decreased collagen synthesis/expression were associated with this connective tissue damage. In a separate group of 53 individuals (80+ y of age), topical application of 1% vitamin A for 7 d increased fibroblast growth and collagen synthesis, and concomitantly reduced the levels of matrix-degrading matrix metalloproteinases. Our findings indicate that naturally aged, sun-protected skin and photoaged skin share important molecular features including connective tissue damage, elevated matrix metalloproteinase levels, and reduced collagen production. In addition, vitamin A treatment reduces matrix metalloproteinase expression and stimulates collagen synthesis in naturally aged, sun-protected skin, as it does in photoaged skin.
  • Article
    The polysaccharides present in Aloe vera gel are presumed to play a key role in the clinical activity of the gel. While clinical studies generally confirm the contribution of the gel to a reduction in inflammation and an acceleration of healing, in some cases the expected therapeutic activity is not observed. This variability could perhaps be attributed to differences in the source of the gel, horticultural conditions and/or post-harvest treatments. Accordingly, polysaccharide content and composition and gel consistency were studied as a function of growth conditions in gels obtained from shrubs of Aloe barbadensis Miller grown in the Negev region of Israel. Autodegradation of the polysaccharides in the freshly produced gel was also characterized, and a method was developed for retarding this process. The polysaccharides were found to consist of glucomannans. Polysaccharides constituted 0.2–0.3% of the fresh gel and 0.8–1.2% of the dry matter content. Irrigation had a greater influence on gel composition than leaf age or season. The fresh gel showed pseudoplastic behaviour, which became Newtonian as a result of post-production autodegradation. The polysaccharides remaining after degradation were mainly mannans. Addition of a natural polysaccharide extracted from a species of red microalgae produced a soft pseudoplastic gel with synergistic rheological properties. The addition of the algal polysaccharide preserved the physical properties of the natural aloe polysaccharides. Chemical means were used to retard microbial degradation.
  • 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 influence of Aloe vera (L.) Burman f. on the glycosaminoglycan (GAG) components of the matrix in a healing wound was studied. Wound healing is a dynamic and complex sequence of events of which the major one is the synthesis of extracellular matrix components. The early stage of wound healing is characterized by the laying down of a provisional matrix, which is then followed by the formation of granulation tissue and synthesis of collagen and elastin. The provisional matrix or the ground substance consists of GAGs and proteoglycans (PGs), which are protein GAG conjugates. In the present work, we have studied the influence of Aloe vera on the content of GAG and its types in the granulation tissue of healing wounds. We have also reported the levels of a few enzymes involved in matrix metabolism. The amount of ground substance synthesized was found to be higher in the treated wounds, and in particular, hyaluronic acid and dermatan sulphate levels were increased. The levels of the reported glycohydrolases were elevated on treatment with Aloe vera, indicating increased turnover of the matrix. Both topical and oral treatments with Aloe vera were found to have a positive influence on the synthesis of GAGs and thereby beneficially modulate wound healing.
  • Article
    We evaluated the time interval required for wound healing using a standard wound management protocol with and without aloe vera gel. Twenty-one women were studied who had wound complications requiring healing by second intention after cesarean delivery or laparotomy for gynecologic surgery. Wounds treated with standard management healed in a mean (+/- SD) time interval of 53 +/- 24 days, whereas those treated with aloe vera gel required 83 +/- 28 days (P = .003). The use of aloe vera dermal wound gel was associated with a significant delay in wound healing compared with treatment with an otherwise identical regimen that did not include aloe vera.
  • Article
    Aloe vera preparations were evaluated for topical anti-inflammatory activity using the croton oil-induced edema assay. The results show that small amounts of A. vera given topically will inhibit inflammation induced by a moderate amount of irritant. In general, the decolorized Aloe was more effective than the colorized Aloe (with anthraquinone). A 47.1% inhibition of inflammation was obtained by 5% decolorized irradiated Aloe. These results may be used as a baseline to assess the biologic activity of A. vera in the treatment of inflammation by podiatric physicians.
  • Article
    We review the scientific literature regarding the aloe vera plant and its products. Aloe vera is known to contain several pharmacologically active ingredients, including a carboxypeptidase that inactivates bradykinin in vitro, salicylates, and a substance(s) that inhibits thromboxane formation in vivo. Scientific studies exist that support an antibacterial and antifungal effect for substance(s) in aloe vera. Studies and case reports provide support for the use of aloe vera in the treatment of radiation ulcers and stasis ulcers in man and burn and frostbite injuries in animals. The evidence for a potential beneficial effect associated with the use of aloe vera is sufficient to warrant the design and implementation of well-controlled clinical trials.