Therapy

Aloe vera
Alan D. Klein, M.D., and Neal S. Penneys, M.D., Ph.D. Miami, FL

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 o f well-controlled clinical trials. (J AM ACAD
DERMATOL 1988; 18:7 14-20.)

Aloe vera, because of its widespread popularity, emodin, an anthraquinone that is a gastrointestinal
has become an ingredient in a wide variety of irritant and acts as a cathartic. Aloe gel is obtained
cosmetic products, including night creams, soaps, from thin-walled mucilaginous cells of the inner
shampoos, suntan lotions, and cleansers. Aloes central zone of the leaf. The gel is the aloe product
have been used medicinally for centuries, yet most most often used by the cosmetic industry because
physicians know little about them and dismiss it contains a variety of organic materials thought
these materials as useless. On the other hand, to contribute to the purported emollient, moistur-
many lay persons believe that aloes have healing izing, and healing effects of the gel.
properties. In a recent survey ~ it was reported that The chemical composition of the aloe plant var-
42 of 124 patients at three urban and three rural ies, depending on species, climate, and growing
primary care clinics in southwestern West Virginia conditions. Using sequential multiple analyzer
used aloe vera in the treatment of common with computer (SMAC) and trace metal analyzers,
ailments. Robson et al. 3 assayed pure aloe vera extract and
S t r u c t u r e a n d leaf contents. Only a few of tbund glucose, uric acid, salicylic acid, creatinine,
more than 3002 known aloe species are currently alkaline phosphatase, cholesterol, triglycerides,
used by the pharmaceutical and cosmetic indus- lactate, calcium, magnesium, zinc, sodium, po-
tries. Aloe barbadensis (miller), also known as tassium, and chloride. Roboz and Hangen-Smith 4
Aloe vera (Linne) (Fig. 1), Aloeferrox (Miller), analyzed the gel portion of Hawaiian aloe vera and
and Aloe perryi (Baker) are most commonly used. found it to contain fat, protein, fiber, 25.5% sugars
The latex portion of the plant, the yellow juice (glucose and mannose), 30% mucilage, and 22.3%
obtained from the pericyclic cells beneath the crude aloin oil and resin.
plant's skin (Fig. 2), is used most frequently in Clinical efficacy. An early report 5 of the use of
the pharmaceutical industry. Latex contains aloe- aloe vera gel was the case of a 31-year-old woman
suffering from severe radiation dermatitis who
had desquamation, burning, and itching over a
From the Departments of Dermatology and Cutaneous Surgery, Uni-
versity of Miami School of Medicine. 4 x 8-cm area on the /eft side of the scalp and
Reprint requests to: Dr. Neal S. Penneys, Box 016940, Miami, FL forehead. Treatment with locally applied fresh
33101, whole leaf of aloe vera reduced burning and itching
714
Volume 18
Number 4, Part 1
April 1988 Aloe vera 715

sp 9

ep
P

cf"

gfb

Fig. 1. A typical example of aloe vera grown in a pot.

Fig, 2. A transverse section near the margin of the aloe leaf. ~p, stoma; ep, epidermis;
p, palisade; cr, calcium oxalate crystals; g, parenchyma; a, pericyclic cells; gfl), vascular
bundle; m, mucilaginous parenchyma. (From Aloe verage: review of aloe vera history,
chemistry, pharmacology. South Hackensack, NJ: Madis Laboratories.)

after 24 hours. By 5 weeks there was complete in Aquaphor applied once daily, (3) a dry gauze
healing of the skin of the scalp and forehead with bandage, and (4) uncovered and untreated. Skin
restoration of sensation and absence of scarring. samples were then removed at varying intervals
Since that report others ~.7 have reported healing of from the irradiated sites. Aloe-treated ulcers
radiation ulcers with applications of fresh whole showed earlier development of necrosis and ul-
leaf of aloe vera. These reports are anecdotal and ceration and earlier reepithelialization than did
have not included well-controlled clinical trials. nontreated control ulcers. Treatment with aloe was
E1 Zawahry et al 8 reported three uncontrolled found to hasten both the degenerative and the re-
cases of chronic leg ulcers of 5, 7, and 15 years' parative phases of the lesions, so that healing of
duration, refractory to other treatments, that re- aloe-treated ulcers occurred in 2 months, while
sponded to the fresh gel of aloe leaves. They con- untreated ulcerations were not completely healed
cluded that the rapid reduction in ulcer size, with 4 months after irradiation. This study would have
complete healing in two of the three cases, sup- been better controlled if an Aquaphor-treated con-
ported aloe vera's healing activity. trol group had been included.
In vivo studies. Lushbaugh and Hale 9 in 1953 Goff and Levenstein, ~~ in 1964, assessed the
studied the effects of aloe vera on acute radio- effects of aloe vera extract upon the healing of
dermatitis following beta irradiation. The epilated surgically induced skin wounds in mice. Their as-
backs of twenty albino rabbits were irradiated in say was the wound strip method in which the force
quadrants with two doses of beta radiation, 14,000 required to separate the edges of a standard seg-
and 28,000 rad. Each quadrant was treated with ment of healing skin was measured. Measurements
one of the four following regimens: (1) fresh whole of the tensile strengths of healing wounds were
leaf of aloe vera applied once daily, (2) aloe vera obtained at 9, 15, and 21 days after wounding from
 Journal of the
716 Klein ana l-'enneys American Academy of
Dermatology

//"5

/
/
/
J

Bradyklnin +Atoe +l~lled Aloe

Y
~r3dykinln
1 fig .':.. ,,,'~ ,,:.oo0 :, 'v r.r~j ~pg

(~; (2) (3) (4)

Fig. 3. The preservation of dermal vasculature after burns by the application of aloe vera
cream. Patent vessels are demonstrated in tissue by the presence of India ink at higher
levels in the aloe-treated animals (left) than in the controls (right). (From Robson MC,
DelBeccaro E J, Heggers JP. The effect of prostaglandins on the derma/microcirculation
after burning, and the inhibition of the effect by specific pharmacological agents. Plast
Reconstr Surg 1979;63:781-7 .)

areas treated with aloe vera extract and from un- Using a modified 14 Weatherly white frostbite
treated control areas. Statistically significant in- model on New Zealand white rabbits, four groups
creases in wound strength in the aloe vera-treated were studied: (1) frostbitten, untreated animals,
wounds at 9 and 15 days were seen, but by 21 (2) frostbitten, treated with aloe vera cream every
days tensile strengths were essentially the same in 8 hours, (3) frostbitten, but treated with meth-
both groups. imazole, 1 mg/kg orally every 8 hours, and
Heggers. and Robson ~ described an experimen- (4) frostbitten, treated with methylprednisolone
tal model to determine if systemic or topical agents every 8 hours. All control rabbits sloughed
that block thromboxane A2 production improved 100% of frostbitten tissue. The mean tissue sur-
tissue survival following either burn or frostbite vival as measured as percentage of frostbitten tis-
injury. Using the Zawacki 12burn model in Hartley sue that survived was 28.2% __+ 26.5% for the
strain guinea pigs, four groups were defined: aloe vera-treated group, 34.3% -4- 15.5% for the
(1) unburned control, (2) burned, untreated con- methimazole-treated group, and 17.5% __ 8.9%
trol, (3) burned and treated with methimazole, for the methylprednisolone-treated group. This
1 mg/kg orally every 8 hours, and (4) burned study demonstrated that aloe vera can enhance tis-
and treated with aloe vera cream topically every sue survival in frostbite injuries in white rabbits.
8 hours. The animals treated in the burn study with In neither portion of the study was a vehicle control
aloe vera cream and methimazole orally had sig- used.
nificantly increased dermal perfusion postburn Robson et al ~3in 1982 tested aloe vera's ability
when compared to controls. Immunohistochemical to inhibit prostaglandin and thromboxane produc-
assessment of thromboxane Az ~ showed mark- tion in the standard guinea pig burn model de-
edly decreased thromboxane A2 levels in treated scribed by Zawacki. ~2 Burn wounds were exam-
groups postbum when compared to untreated con- ined immunohistochemically for the presence of
trois. This portion of the study demonstrated that prostaglandins and thromboxanes. In aloe vera-
aloe vera cream can increase dermal perfusion and treated burn wounds, no thromboxane B2 could
apparently decrease thromboxane A2 quantities in be demonstrated at 8, 24, and 72 hours post-
burn wounds in guinea pigs. burn, while in untreated burn wound controls
Volume 18
Number 4, Part 1
April 1988 Aloe vera 717

NO 0 OH NO 0 Ok
ALOE EXTRACT
N~C~ O H
0 o
@
EMODIN CHRYSOPHANIC ACID 8
,m
w,-
8
HO OH HO 0 .E 60
C |
[ ~ CHzOH @
0 O
ALOE- E MODIN
A 0 o 8
HO 20 8 *
H OH
ALOIN (BARBALOIN)
i i | J i

ON-, OH OH 017 0.42 OB3

0 ,,.,. 0~ --, 0 mg/ml
CHIEF SAL ICYLIC
PROOUCT AClO Fig. 5. Tricyclic compounds found in aloe and the Kolbe
KOLBE REACTION reaction. (From Robson MC, Heggers JP, Hagstrom
WJ. J Bum Care Rehab 1982;3:157-62.)
Fig. 4. Inactivation of bradykinin by aloe extract. The
curves represent the contraction of guinea pig ileum
after addition of the various compounds. (From Fu-
jita K, Shosuke I. Biochem Pharmacol 1976;25:205.) Whether the carboxypeptidase from aloe can in-
hibit bradykinin in vivo, thereby decreasing pain
at the site of acute inflammaton, has not yet been
thromboxane B2 became detectable in significant demonstrated.
amounts 2 hours postburn and 8, 24, and 72 hours Salicylic acid has been demonstrated in aloe
postbum. PGF2,~ levels were also decreased in aloe- vera by Robson et aP and also in organic com-
treated wounds at 8, 24, and 72 hours compared pounds such as emodin, aloe-emodin, and aloin,
to controls, while PGE2 levels were increased com- all of which can be broken down by the Kolbe
pared with controls. Thomboxanes and prosta- reaction t7 to form salicylates (Fig. 5). Salicylates
glandins have been shown to elicit platelet aggre- are both analgesic and anti-inflammatory, inhib-
gation, leukocyte adherence, and vasoconstric- iting the production of prostaglandins from ara-
tion, properties that may be detrimental to burn chidonic acid by inhibiting cyclooxygenase. Is In
wound healing by enhancing ischemia. Aloe vera's 1981 Penneys 19 demonstrated that both aloe vera
ability to inhibit thromboxane B2 and PGF2, for- gel and commercial aloe vera extract significantly
mation in pig burn wounds would preserve dermal inhibited the oxidation of arachidonic acid in vitro
circulation and decrease burn wound tissue loss (Figs. 6 and 7).
(Fig. 3). If these data are extrapolated to man, Magnesium lactate 2~is in aloe vera. Magnesium
this could serve as a rationale for the application lactate inhibits the in vivo conversion of histidine
of aloe extracts to radiation and thermal wounds to histamine in mast cells by inhibiting histidine
and possibly to other situations in which there may decarboxylase. ~ Histamine, a known vasodilator,
be compromise of blood flow in the skin. is regarded as one of the major producers of itching
Pharmacologic studies. At least four pharma- in the skin. Inhibition of histidine decarboxylase
cologically active ingredients have been identified by magnesium lactate in aloe may result in an
in aloe vera. Fujita and Shosuke 15 in 1976 re- antipruritic effect.
ported that aloe significantly inactivated bradyki- Bacteriologic and fnngal studies. In 1964 Lor-
nin in vitro (Fig. 4). In 1979 Fujita et al ~6reported enzetti et aF 2 studied the bacteriostatic properties
the enzyme to be a carboxypeptidase, capable of of a freeze-dried preparation of aloe juice by agar
hydrolyzing bradykinin and angiotensin I in vitro. diffusion technique with the use of the following
Bradykinin is both a vasodilator and a potent pain- organisms: Staphylococcus aureus 209, Esche-
producing agent at the site of acute inflammation. richia coli, Streptococcus pyogenes, Corynebac-
 Journal of the
718 Klein and Penneys American Academyof
Dermatology

~*~2g~-L~-~"~-~c~-'~-~,r162 ":.-:,.... "( 9 .~'~-- ,-, . . . . . v.*,'

- - ~1, . .~'~r~ .... ~r' ' '4~'~.~.'"

Figs. 6 and 7. The inhibition of cyclooxygenase in vitro by increasing quantities of aloe

gel. (From Penneys NS. Acta Derm Venereol (Stockh) 1981;62:59-61.)

"/e-, Table I. Antimicrobial effects of aloe vera

P
I n~m* J extract in cream base compared to silver
sulfadiazine in agar well diffusion (zone

iii_
-- I,,IS n,~/~ f
, n 11.$, .,,s/.v
sizes measured in ram)*
Aloe
Organisms vera AgSD

Gram-negative
E. Coli 16 12
E. cloacae 14 12
K. pneumoniae 14 6t
P. aeruginosa 17 12
I|- Gram-positive
S. aureus 18 12
e
S. pyogenes t6 12
S. agalactiae 16 12
I tl 11 S. faecalis 6 11
DAYS B. subtilis 19 14
Fig. 8. Inhibition of the growth of T. mentagrophytes AgSD: Silver sulfadiazine.
by increasing quantities of whole leaf aloe powder. *From Robson MC, Heggers JP, Hagstrom WJ. J Burn Care Rehab
(From Fujita K, Yamada Y, Azuma K, Horozawa S. 1982;3:157-62.
Antimicrob Agents Chemother 1978;14:132-6.) tAgar well is 6 mm in diameter.

terium xerose, Shigella paradysenteriae, Salmo- concentrations. Twelve different species of organ-
nella typhosa, Salmonella schottmiilleri, and Sal- isms were inoculated into different concentrations
monella paratyphi. Aloe significantly inhibited of the extract. As low as 60% aloe vera extract
growth on plates inoculated with S. aureus 209, was found to be bactericidal against Pseudomonas
S. pyogenes, C. xerose, and S. paratyphi. aeruginosa, Klebsiella pneumoniae, Serratia mar-
Robson et al 3 in 1982 assayed the antimicrobial cescens, Citrobacter species, Enterobacter cloa-
properties o f aloe vera extract measuring both cae, S. pyogenes, and Streptococcus agalactiae.
mean inhibitory concentrations and mean lethal Seventy percent concentrations of aloe were bac-
Volume 18
Number 4, Part 1 Aloe vera 719
April 1988

tericidal for S. aureus, 80% for E. coli, and 90% cure or alleviate a variety of unrelated conditions,
for Streptococcus faecalis and Candida albicans. including colitis, bursitis, asthma, arthritis, stom-
Bacillus subtilis was not inhibited by aloe vera ach ulcers, varicose veins, sunburns, and insect
extract. To summarize this work, in vitro bacte- bites, remain unsubstantiated.
ricidal activity against organisms frequently iso- In summary, there is scientific evidence sup-
lated from wounds has been demonstrated for aloe porting aloe vera's bactericidal and antifungal ac-
vera (or a component from aloe vera); however, tivity in appropriate concentrations in vitro. This
whether this material is efficacious in vivo is still has not been demonstrated in humans in vivo.
to be determined. In vivo bactericidal activity has There is evidence suggesting that aloe vera does
not been studied. contain several pharmacologically active ingredi-
The Nathan agar well23 technique was used ents, including a carboxypeptidase that inhibits
to test the susceptibility of some organisms bradykinin in vitro, salicylates, and a substance
to aloe vera cream, comparing the effects of that inhibits thromboxane B~ in vitro. The trans-
aloe vera-containing cream with silver sulfadi- lation of these in vitro effects to clinical situations
azine. Effects of aloe vera cream are comparable has not been demonstrated. Several studies and
to those of silver sulfadiazine, as shown in Ta- case reports provide some support for claims of
ble [. aloe vera's benefit in the treatment of radiation
Fujita et a124 in 1978 reported inhibitory effects ulcers and clinical stasis ulcers in humans and burn
of both a powder of the aloe leaf and a high mo- and frostbite wounds in animals. Well-controlled
lecular weight component of aloe on the growth clinical trials in humans must be carried out with
and morphology of Trichophyton mentagrophytes the use of a standardized preparation of aloe vera
in vitro. At concentrations greater than 25 mg/ml before aloe vera's use can be recommended in the
of whole aloe leaf, growth was completely inhib- treatment of any skin condition; however, the ev-
ited (Fig. 8). The minimal inhibitory concentration idence for aloe vera's beneficial effects is ample
of the high molecular weight component of aloe enough to warrant further clinical trials.
against these strains of T. mentagrophytes was 10
mg/ml.
REFERENCES
Complications associated with the use of aloe.
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uses. Springfield: Charles Thomas, 1972.
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 Journal of the
720 K l e i n and P e n n e y s American Academy of
Dermatology

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