Mechanism of Action

Constituents: The gel or mucilage obtained from the flesh of the leaf is 99% water
at pH 4.5. Many of the health benefits associated with aloe (promotion of wound
healing, antifungal activity, hypoglycemic effects, antidiabetic effects, antiinflammatory effects, anticancer effects, immunomodulatory effects, and
gastroprotective properties) are attributed to the polysaccharides contained in the
gel of the leaves (30700, 101). The constituent polysaccharide glucomannan is an
effective human skin moisturizer, which accounts for its use in many cosmetics.
Acemannan, the major carbohydrate fraction in the gel, is a water-soluble longchain mannose polymer, which has been found in vitro and in animal studies to
modulate immune function (particularly macrophage activation and cytokine
production) and to accelerate wound healing. The macrophage-stimulating principle
of acemannan appears to reside in the high-molecular-weight polysaccharide
aloeride (30668). Acemannan has also been reported to exhibit antineoplastic and
antiviral effects in vitro.

Pentaketide chromone synthase and octaketide synthase have been isolated from
aloe (30701). Other constituents include bradykininase, which possesses antiinflammatory properties, and magnesium lactate, which has antipruritic effects
(30739). A mannose-rich polysaccharide fraction of aloe gel has been shown in
mice to enhance antibody production (30730). Salicylic acid and other
antiprostaglandin compounds may be responsible for aloe's local anti-inflammatory
activity, possibly due to an inhibitory effect on the arachidonic acid pathway via
cyclooxygenase (30747).

Maloyl glucan compounds isolated from Aloe barbadensis Miller include 6-O-(1-Lmaloyl)-alpha-,beta-D-Glcp (veracylglucan A), alpha-D-Glcp-(1-->4)-6-O-(1-Lmaloyl)-alpha,-beta,-D-Glcp (veracylglucan B), and alpha-D-Glcp-(1-->4)-tetra-[6-O(1-L-maloyl)-alpha-D-Glcp-(1-->4)]-6-O-(1-L-maloyl)-alpha,-beta-D-Glcp
(veracylglucan C) (30686). In in vitro research, veracylglucan B demonstrated
potent anti-inflammatory and antiproliferative effects, while veracylglucan C
exhibited significant cell proliferative and anti-inflammatory activities. Veracylglucan
B and C appeared antagonistic and competitive in their effects on cell proliferation.

Antifungal effects: A hydroalcoholic extract of fresh Aloe vera leaves had a

minimum fungicidal concentration (MFC) between 80 and 100mcL/mL against the
mycelial growth of Botrytis gladiolorum, Fusarium
oxysporum f.sp. gladioli,Heterosporium pruneti, and Penicillium gladioli (30692).

Anti-inflammatory effects: According to reviews, Aloe vera has demonstrated

anti-inflammatory effects (30714, 30709,8224). Its use for inflammation specific to
osteoarthritis has also been reviewed (30709). Topical aloe's anti-inflammatory
properties do not appear to interfere with wound healing but rather increase wound
tensile strength (30741), possibly due to the fibroblast-stimulating activity of
mannose-6-phosphate (30742). In vivo, Aloe vera gel (97.5%) significantly reduced
ultraviolet (UV)-induced erythema after 48 hours, being superior to 1%
hydrocortisone in placebo gel. In contrast, 1% hydrocortisone in cream was more
efficient than Aloe vera gel (19770). Aloe also has antithromboxane activity, yet it
maintains the prostaglandin ratio without causing injured blood vessels to collapse.

Antilipemic effects: In human research, participants receiving Aloe vera showed

decreased levels of total cholesterol (15.4-15.5%), low-density lipoprotein (LDL)
cholesterol (18.2-18.9%), and triglycerides (25.2-31.9%) compared to baseline.

Information regarding between-group differences was lacking (12164). Aloe has

demonstrated further antilipemic effects in other human research (19756, 30762).

Antimicrobial effects: According to a review, aloe has demonstrated antimicrobial

effects (101). In vitro, a commonly used topical oral agent, acemannan (Aloe vera)
hydrogel rinse, was evaluated for its antimicrobial effects against Staphylococcus
aureus, group B Streptococcus, Escherichia coli, and Candida albicans (30717).
Further information is lacking.

In mice, daily application of honey and Aloe vera gel protected against burn wound
infection (p<0.001) (30707). In combination with the Klebsiella pneumoniae B5055
phage, however, a lack of additional benefit was noted (p>0.05) compared to use of
honey and Aloe vera alone.

In vitro, a copper biocide and Aloe vera-based biocidal hand rub (Xgel) reduced
colony-forming units (CFU) of methicillin-resistant Staphylococcus aureus (MRSA)
and Acinetobacter by >108 CFU in one minute; Xgel produced a 3 x 103 reduction
inC. difficile spore CFU (30702).

Antineoplastic effects: The antileukemic and antimutagenic effects of aloe in

vitro have been attributed to di-(2-ethylhexyl) phthalate (DEHP) (30666). Promotion
of apoptosis has been reported in vitro as a possible antineoplastic mechanism
(30673). Aloe appears to affect detoxification of reactive metabolites by liver and
other organs (30667). The anthraquinone glycosides have been studied for their
cytotoxic effects (30687). For instance, aloe-emodin induced apoptosis in T24
human bladder cancer cells, which is thought to be mediated through the activation
of p53, p21, Fas/APO-1, Bax, and caspase-3 (30688). In human malignant
melanoma cells, aloe-emodin inhibited NAT1 activity in intact cells in a dosedependent manner (30685). In human lung carcinoma cells, aloe-emodin is thought
to induce DNA damage through generation of reactive oxygen species (30684).
Based on in vivo angiogenesis assays, Crdenas et al. reported that aloe-emodin
may behave as both an antitumor and an antiangiogenic compound (30689). Aloeemodin is thought to inhibit endothelial cell proliferation, but this effect is not cell
specific, since aloe-emodin also inhibits tumor cell proliferation. Cell migration and
invasion are not remarkably affected by aloe-emodin. On the other hand, aloeemodin has different effects on endothelial and tumor cell gelatinases. Two main
targets of the pharmacological action of aloe-emodin as an antiangiogenic
compound seem to be urokinase secretion and tubule formation of endothelial cells.

Antiviral effects: According to a review, significantly more patients were cured

when treated with Aloe vera cream (67-70% cured) or Aloe vera gel (45% cured at
7.0 days) vs. placebo cream (7-7.5% cured, p<0.02) (12164). Also, the average
healing time was significantly shorter with Aloe vera cream (4.8-4.9 days) or Aloe
vera gel (7.0 days) vs. placebo (12-14.0 days).

Antioxidant effects: Antioxidant properties have been attributed to aloesin derived

from Aloe vera (30672, 30667, 30671). In cell-line research, APS-1, a
polysaccharide from Aloe vera var. chinensis also showed free radical-scavenging
and other antioxidant properties (30682).

Cardiovascular effects: Calcium isocitrate, isolated from Aloe saponaria, has

been shown to be inotropic in rat and rabbit hearts (30739).

Dermatological effects: In a study of topical application for up two weeks, Aloe

barbadensis Miller extracts increased the water content of the stratum corneum of

the arms of human volunteers, although transepidermal water loss was not altered
(19758). According to a review, significantly more psoriasis patients treated
with Aloe vera were considered cured after treatment vs. those receiving placebo
cream (83.3% vs. 6.6%, respectively, p<0.001) (12164). In human research,
complete response was lacking for all subjects with psoriasis in the study (19741).
However, Aloe vera treatment reduced Psoriasis Area Severity Index (PASI) scores
significantly more than triamcinolone over eight weeks (1.1, 95% CI: -2.13 to -0.16,
p=0.0237). Both treatments were equally efficacious at reducing Dermatology Life
Quality Index (DLQI) score scores (p=0.5497). The authors concluded that
treatment with Aloe vera may improve clinical symptoms of psoriasis more
effectively than triamcinolone acetonide, although both treatments resulted in
similar improvements in quality of life. In humans, local irritation was reported in
40% of the aloe group (and 44% of the silver sulfadiazine group) (30769).

Gastrointestinal effects: According to a review, Aloe vera may be a protective

agent against the adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs)
in the gastrointestinal tract (30709).

Hepatic effects: InHUMAN research, following treatment with aloe, the placebo
group still had average fibrosis with inflammatory cell infiltration, but the aloe (AHM)
group had reduced fibrosis and inflammatory cell infiltration compared to the
placebo group (19780). At the end of the study, participants with either hepatitis B
or hepatitis CVIRUS who were treated with AHM showed more significant
reduction in the liver enzyme levels vs. the placebo group (p<0.05). After treatment,
both the placebo and the AHM groups had significant decreases in
malondialdehyde levels compared to baseline (p<0.05), but only the AHM group
showed significant increase in glutathione levels (p<0.05). Before treatment, serum
levels of transforming growth factor (TGF)-beta1, hyaluronic acid (HA), and matrix
metalloproteinase (MMP)-2 were significantly elevated in patients with fibrosis
compared to the healthy control group. After treatment, significant reductions in
these fibrosis markers were experienced by participants in the placebo and AHM
groups (p<0.05).

Hypoglycemic effects: Constituents of Kitachi aloe leaf pulp and skin have been
found to stimulate beta-cells inDIABETIC mice, thereby lowering blood glucose
levels (30758). In human research, compared to the placebo group following
treatment, participants administered Aloe vera showed reduced mean glucose
levels (+5.2 25.1% vs. -4.8 14.7% change), and reduced HbA 1C ( 8.6 24.0%
change vs. -8.1 18.0%) (19756). In humans, participants in the control group
lacked statistically significantCHANGES in blood glucose levels, while participants
who received aloe showed a statistically significant reduction in blood glucose
levels (from 250mg% to 141mg%) (12164).

Laxative effects: Aloe latex contains anthraquinone glycosides (aloin, aloeemodin, and barbaloin) that act as potent stimulant laxatives
(30725, 19742, 19743, 30772, 30773, 30745, 19744). These water-soluble
glycosidesARE split by intestinal bacteria into aglycones, which are believed to
exert a more powerful laxative effect than other herbs, including senna, cascara, or
rhubarb root. One of these compounds, aloe-emodin-9-anthrone, has been shown
to increase the water content in rat large intestines (30718). This appears to be a
more important cathartic mechanism than increased intestinal motility (which has
also been proposed) (19742, 19743).

Radioprotective effects: Wang et al. suggested that aloe polysaccharides may

have a radioprotective effect on nonmalignant cells via modulation of the cell cycle
(30683, 30677).

Wound healing effects: In a case study, the use of a compound consisting of

collagen and Aloe vera in a patient with an ischemic wound was well accepted
(30708). In a laboratory study, Aloe vera was the most adsorbent in a series of
biopolymers tested and promoted a moist wound environment (30705). According
to a review, participants with acne vulgaris who were treated with Aloe vera healed
about 72 hours faster than the patients in the control group (12164). However, a
statistically significant between-group difference was lacking. Also, it was reported
that Aloe vera treatment constricted the blood vessels, reduced edema, and
reduced crusting and pus by day 4. On day 5, 90% of the aloe-treated acne was
healing vs. 40-50% of that in participants in the control group. In another study,
patients who received gynecological surgery experienced reduced healing time with
standard wound care vs. standard wound care plus aloe treatment (53 days vs. 83
days, respectively, p<0.003).

Pharmacokinetics

Absorption: In vitro, South African aloes (Aloe ferox, A. marlothii, and A. speciose)
have been investigated as enhancers of drug permeation (30724). The aloe gel
material decreased transepithelial electrical resistance of excised rat intestinal
tissue in a statistically significantly manner, but it lacked an ability to increase
atenolol transport across the tissue model. Some of the aloe gel materials
increased FITC-dextran transport across Caco-2 cell monolayers in a statistically
significantly manner.

The whole leaf or inner gel liquid preparations of aloe have been used to enhance
the intestinal absorption and bioavailability of coadministered compounds, as well
as enhancement of skin permeation (30700). Dried Aloe vera gel powder has been
used as an excipient in sustained-release pharmaceutical dosage forms.

Anthraquinone glycosides, whichARE absorbed well only after digestion by

intestinal bacteria, are eliminated in the urine, bile, feces, and breast milk.

The half-life of aloe-emodin is approximately 48-50 hours (30744).