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logic activities.
loe vera (Aloe barbadensis Miller) is a perennial
succulent belonging to the Liliaceal family. It is a
cactus-like plant that grows in hot, dry climates.
In nature, it may be damaged physically by ultra-
violet (UV) irradiation or by insects. Perhaps its
Seongwon Choi, PhD: Professor, Depart- survival in a harsh environment encourages people to believe that
ment of Pharmachology, Seoul National
University College of Medicine, Seoul, Ko-
aloe vera has wound-healing and antibiotic effects. It is, therefore,
rea less than fortuitous that aloe vera has been reported to possess
Myung-Hee Chung, MD, PhD: Professor, immunomodulatory, antiinflammatory, UV protective, antiproto-
Department of Pharmacology, Seoul Na-
tional University College of Medicine,
zoal, and wound- and burn-healing promoting properties.1 How-
Seoul, Korea ever, previous treatments of such diseases and conditions with
Correspondence: M-H Chung, MD, PhD, aloe vera gel have been empirical rather than theoretical. There-
Professor, Department of Pharmacology,
Seoul National University College of Medi- fore, the clarification of the modes of action of the biochemical
cine, Seoul 110-799, Korea. Phone: (82)- components of aloe vera is important in the determination of the
(2)-740-8294, FAX: (82)-(2)-745-7996
most efficient way of using such active species effectively and
Email: mhchung@snu.ac.kr
developing their applications. It is essential to establish the rela-
tionships between the components of aloe vera and their pharma-
2003 Elsevier Inc. All rights reserved. cologic effects. Many attempts have been made to isolate single,
0749-2081/03/101-0001$30.00/0 active components to examine their effects and clarify their func-
10.1016/S1543-1150(03)00005-X
tional mechanisms. Reynolds review1 describes the biologic activ-
54 CHOI AND CHUNG
ities of several aloe species. Since then, further observed when a wound was treated with aloe vera
pharmacologic activities of the components of gel.14 In another trial, aloe vera gel hindered
aloe vera have been reported. Therefore, this re- wound healing in an experimentally induced sec-
view focuse on establishing the relationship be- ond-degree burn.15 Different results should be ex-
tween the components of aloe vera and their ef- pected, however, given the fact that the composi-
fects based on published reports and more recent tion of the aloe vera gel varies and that even
findings. within the same species the plant depends on
source, climate, region, and the processing
method. Nevertheless, as more factors involved in
BIOLOGIC ACTIVITIES OF ALOE VERA GEL the wound healing process are discovered, data
accumulates supporting the enhancing effect of
wound-healing and antiinflammatory ingredient was found to induce the expression of mRNAs
in aloe vera. Mice receiving 300 mg/kg of man- encoding IL-1 and TNF-.67 These polysaccha-
nose-6-phosphate had improved wound healing rides may exhibit antitumor and antiviral activ-
over saline controls. Grey et al34 suggested that ities through enhanced immune attack and im-
mannose-6-phosphate linked to a protein produce munemodulation.68
even greater wound-healing effects. Carcinogenesis induced by DNA adduct forma-
Acemannan (ie, aloe polymannose, a polydis- tion was shown to be inhibited by a polysaccha-
persed -(1,4)-linked acetylated mannose-con- ride-rich aloe gel fraction in an in vitro rat hepa-
taining complex carbohydrate) was found to have tocyte model.69 Kim et al69 reported on the
immunomodulatory activity.57 It was reported to chemopreventive effect of aloe polysaccharide iso-
activate macrophages; enhance cytokine release; lated from aloe vera noting that oxidative DNA
stimulate interactions between macrophages, T- damage assessed by 8-hydroxyguanosine was sig-
lymphocytes and B-lymphocytes; and enhance nificantly reduced by the polysaccharide, which
the generation of cytotoxic T-lymphocytes. Ace- also inhibited benzo[a]pyrene-DNA adduct forma-
mannan was also found to potentiate antibody tion by interfering with benzo[a]pyrene-DNA ab-
production against coxsackie virus and reduce sorption in vivo. This may be due to the inhibition
radiation-induced skin reactions in C3H mice.58 of carcinogen activation systems or to the induc-
Acemannan enhanced the allo-responsiveness of tion of detoxifying enzymes.70
human lymphocytes59 and induced the pheno- Cutaneous exposure to high doses of UVB radi-
typic and functional maturation of immature den- ation induces the systemic suppression of contact
dritic cells.60 It also upregulated phagocytosis and hypersensitivity responses to hapten applied to
the candidicidal activity of macrophages.61 Re-
non-irradiated sites and of delayed-type hypersen-
garding its mechanism, acemannan induced no
sitivity responses to infectious agents.71 UVB ra-
synthesis, which was mediated by macrophage
diation contributes to the growth of highly anti-
mannose receptors in chickens,62 stimulated the
genic skin cancers by suppressing T-cell mediated
synthesis of monokines, and initiated immune
immune responses.72 Therefore, susceptibility to
response.63 It also showed inhibitory effects on
UV-induced immune suppression of contact hy-
tumor growth, that is, murine sarcoma implanted
persensitivity responses may be a risk factor for
in mice regressed after acemannan treatment,
the development of skin cancer in humans.73
which was probably due to an immune attack and
Therapeutic intervention to prevent immune sup-
enhanced immunomodulation.63
The ability of aloe vera to stimulate the immune pression may reduce the risk of skin cancer.74
system is attributed to polysaccharides present in Aloe oligosaccharides and polysaccharides were
the aloe vera gel.22 There has been some disagree- found to inhibit UV-induced immune suppression
ment concerning the identities of the active ma- and interleukin-10 production.75 Aloe oligosac-
terials, thus, the optimal form and composition of charides may prevent UV-induced suppression of
the aloe polysaccharides has been investigated to delayed-type hypersensitivity by reducing kera-
maximize immunomodulatory activity and stabil- tinocyte derived immunosuppressive cytokines.74
ity. In one study the immunomodulatory activity It is also suggested that aloe oligosaccharide pro-
of aloe vera was found to be caused by a 15 kDa tects against delayed type hypersensitivity re-
polysaccharide,64 while modified aloe polysaccha- sponse indirectly by inducing immunostimulatory
ride with an average molecular weight of 80 kDa cytokines, such as interleukin-12.76
showed the highest protective activity against The labile natures of factors that prevent im-
UVB irradiation-induced immune suppression. mune suppression vary in different gel extract
The native polysaccharide is of 2000 kDa with a preparations and is possibly influenced by the
mannose:galactose:glucose ratio of 11:0.2:1, manufacturing process used.74 Variable activities
whereas the active form is of 80 kDa with man- in the reported experiments possibly result from
nose:galactose:glucose ratio of 40:1.4:1. The ac- the degradation of polysaccharide resulting from
tive polysaccharide is composed of mannose at a bacterial contamination or endogenous enzyme
high ratio. Polysaccharides are also known to activity in aloe vera gel. These explain some of the
possess antitumor effects.65,66 A high molecular difficulties that investigators have experienced in
weight polysaccharide (aloeride) was found to terms of result reproducibility when using unfrac-
have potent immunostimulatory activity, and tionated leaf gel from aloe vera.
RELATIONSHIP BETWEEN ALOE VERA COMPONENTS AND THEIR BIOLOGIC EFFECTS 59
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