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Aloe Vera – A Review of Toxicity and Adverse Clinical Effects
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DOI: 10.1080/10590501.2016.1166826
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Aloe vera: A review of toxicity and adverse clinical

effects
Xiaoqing Guo & Nan Mei
To cite this article: Xiaoqing Guo & Nan Mei (2016) Aloe vera: A review of toxicity and
adverse clinical effects, Journal of Environmental Science and Health, Part C, 34:2, 77-96, DOI:
10.1080/10590501.2016.1166826
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Download by: [FDA Library] Date: 11 May 2016, At: 04:11

JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH, PART C
, VOL. , NO. , –
http://dx.doi.org/./..
Aloe vera: A review of toxicity and adverse clinical effects

Xiaoqing Guo and Nan Mei
Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, Jefferson,
Arkansas, USA
ABSTRACT KEYWORDS
The Aloe plant is employed as a dietary supplement in a variety of Aloe gel; aloe latex; Aloe vera;
foods and as an ingredient in cosmetic products. The widespread carcinogenicity; genotoxicity;
human exposure and its potential toxic and carcinogenic activi- toxicological effects
ties raise safety concerns. Chemical analysis reveals that the Aloe
plant contains various polysaccharides and phenolic chemicals,
notably anthraquinones. Ingestion of Aloe preparations is asso-
Downloaded by [FDA Library] at 04:11 11 May 2016
ciated with diarrhea, hypokalemia, pseudomelanosis coli, kid-

ney failure, as well as phototoxicity and hypersensitive reactions.
Recently, Aloe vera whole leaf extract showed clear evidence of
carcinogenic activity in rats, and was classified by the Interna-
tional Agency for Research on Cancer as a possible human car-
cinogen (Group 2B). This review presents updated information on
the toxicological effects, including the cytotoxicity, genotoxicity,
carcinogenicity, and adverse clinical effects of Aloevera whole leaf
extract, gel, and latex.
1. Introduction
The use of herbal products has been growing rapidly in the general population.
In 2007, the National Health Interview Survey reported that approximately 40%
of Americans, including adults and children, used complementary and alternative
medicine as alternative therapy in the past 12 months.[1] About US $14.8 billion
was spent on the purchase of nonvitamin, nonmineral natural products, which
accounted for 44% of all out-of-pocket costs for complementary and alternative
medicine.[2] Aloe has enjoyed a long history of providing a myriad of health ben-
efits, and is one of the most frequently used herbal remedies employed through-
out the world. There are more than 400 species of Aloe, but the most popular and
widely used species is Aloe barbadensis Miller (also called Aloe vera Linne, com-
monly referred to Aloe vera). Aloe is derived from the Arabic word alloeh meaning
“bitter and shiny substance,” and vera from the Latin word for “truth.” Other species
used in health and medicine include but are not limited to Aloe arborescens Miller (a
member of the asphodelacea family), Aloe perryi Baker, Aloe andongensis, and Aloe
ferox.[3,4]
CONTACT Nan Mei Nan.Mei@fda.hhs.gov Division of Genetic and Molecular Toxicology, National Center for
Toxicological Research,  NCTR Road, Jefferson, AR , USA.
This article not subject to US copyright law.
78 X. GUO AND N. MEI
Aloe vera, a genus within the Liliaceae family, is a stemless or very short-stemmed
perennial succulent or xerophyte with elongated and peaked leaves in which large
amounts of water are stored in the tissue.[5] The green fleshy leaves range in height
from a few centimeters to 2–3 meters or more and have three identifiable layers. The
outer layer is a thick cuticle or rind accounting for about 20%–30% by weight of the
whole plant leaf. It consists of up to 18 layers of cells interspersed with chloroplasts
where carbohydrates, fats, and proteins are synthesized. The outer leaf pulp, a thin,
mucilaginous layer just beneath and adjacent to the thick rind, contains vascular
bundles acting as the transport system for the plants. Three types of tubular
structures compose the vascular bundles: xylem, which moves water and minerals
from the roots to the leaves; phloem, which takes synthesized minerals to the
roots; and the pericyclic tubule, which stores and transports bitter yellow latex
(often referred to as Aloe sap) along the margin of the leaf. The number of these
bundles varies based on the size of leaves.[6] The inner leaf pulp makes up the
majority of the plant by volume, and is composed of large thinwalled parenchymal
cells containing Aloe vera gel, a synonym to inner leaf, inner leaf fillet, or fillet.
Aloe contains pharmacologically active ingredients associated with diverse bio-
logical activities including fungicidal, antiviral, antibacterial, anti-inflammatory,
antimicrobial, laxative, immunomodulating, and anticancer effects.[3] Aloe vera,
known as the “plant of immortality” in early Egypt, has been used as a traditional
medicine in Arab, Chinese, Egyptian, Greek, Indian, Japanese, Korean, and Roman
cultures[7,8] for more than 2000 years to empirically treat a broad list of disorders
and ailments, such as skin problems (wounds, x-ray and radium burns, and psoria-
sis), constipation, external and internal ulcers, hyperlipidemia, diabetes, and lupus
erythematosus.[9–12] Due to the numerous purported beneficial effects, Aloe vera
production has been an emerging industry for making laxative drugs, cosmetics,
and functional food, such as face and hand creams, foundations, cleansers, lipsticks,
suntan lotions, shampoos and hair tonics, shaving preparations, bath aids, makeup
and fragrance preparations, baby lotions and wipes, yogurt, drinks, capsules, and
tablets. In order to show current pharmacological and/or toxicological research sta-
tus on Aloe, we performed a literature search in PubMed using “Aloe” and specific
country names as key words (Table 1). A total of 1895 and 975 publications were
identified when using “Aloe” as key word in All Fields Not Author and MeSH term
databases, respectively. More than half (51%–60%) of these studies were conducted
in the top 10 countries (Table 1), and about one third of them are from five Asian
countries, including China, India, Japan, Korea, and Iran. However, only about 8%
of these articles investigated Aloe-related toxicity in vitro and in vivo (Table 1).
Although Aloe vera has long been considered as a safe functional food material
that can be used orally and topically,[13] on many occasions it has not been as safe as
commonly thought. Recently, the reported adverse effects in humans and toxicity,
genotoxicity, and carcinogenicity in both in vitro and in vivo studies raise questions
as to whether the components in Aloe vera may have tumor-promoting activities in
humans. Due to its widespread human exposure and concerns that some compo-
nents may cause cancer, in 1998 the National Cancer Institute nominated Aloe vera
JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH, PART C 79
Table . Pharmacological and/or toxicological research on Aloe based on PubMed online search. ∗
Country All fields# MeSH term
Aloe All  

China  
India  
USA  
Japan  
South Africa  
Korea  
Iran  
Italy  
UK  
Brazil  
Top  countries  (%)  (%)
Toxicity-related  (%)  (%)
∗Searched on July , .
#All fields but not in authors.
as a high-priority candidate for a carcinogenicity study under the National Toxicol-

ogy Program (NTP). In 2002, the US Food and Drug Administration (FDA) issued
a final rule stating that use of Aloe as a nonprescription laxative drug is no longer
generally recognized as safe and effective.[14] Recently, Aloe vera whole leaf extract
has been classified by the International Agency for Research on Cancer as a possible
human carcinogen (Group 2B), along with other natural products such as Ginkgo
biloba extract and kava extract.[15,16]
The Aloe vera whole leaf extract, as well as the two primary components (the gel
and the latex or exudates) of the leaf, have been used for various reasons in tradi-
tional medicine. Generally, the gel is used topically to soothe wounds, burns, and
skin irritations, and the latex is recognized to possess cathartic effects. Nevertheless,
there is still some confusion surrounding the whole leaf extract, the gel, and the
latex. Given that the beneficial properties of Aloe vera have been addressed compre-
hensively and that the gel and the latex possess distinct components and medical
purposes,[5] in this article, the whole leaf extract, the gel, and the latex associated
toxicity, genotoxicity, and carcinogenicity both in vitro and in vivo are reviewed,
and adverse clinical effects in humans are also summarized.
2. Aloe vera whole leaf extract
2.1 Components
Aloe vera whole leaf extract, including the gel and the latex, contains more than
200 chemical substances.[4] The raw Aloe leaf is composed of approximately 98.5%
water, the remaining solid material contains a range of compounds including nutri-
ents (e.g., carbohydrates, amino acids, vitamins, and minerals) and non-nutrients
(e.g., organic acids, lignins, phenolic compounds, anthraquinones, and phytos-
terols). The chemical composition and the potency of the various constituents are
influenced by many factors, such as species/subspecies, climate, land and irrigation,
cultivation methods, harvesting, extraction processing, and storage conditions.[4,5]
Figure . Representative reversed-phase HPLC profiles of Aloe vera whole leaf extract and decolorized
whole leaf extract. Five mg/ml samples were dissolved in Fischer’s medium with pH adjusted to .–
.. HPLC analysis was performed using a Phenomenex Prodigy  μm ODS column (. mm ×  mm)
eluted with methanol with a linear gradient of %–% water over  min and –% methanol over
 min at a flow rate of  ml/min.
To determine whether the presence of the latex alters the physical and chemical
properties in whole leaf extract, the decolorized Aloe vera whole leaf has been stud-
ied for its toxicity and potential carcinogenicity. The decolorized extract was pre-
pared by activated carbon-adsorption of the whole leaf extract (1%, w/w) to remove
the latex portion of the plant, mainly anthraquinones, the components giving Aloe
vera its laxative properties. However, some of the high molecular weight polysaccha-
rides of the inner leaf Aloe gel can also be removed by charcoal absorption. Chemi-
cal analysis revealed that the concentrations of aloin, the principle anthraquinone of
Aloe vera latex, differed bya factor of 100 in unfiltered and filtered extracts (8 mg/g
for whole extract and 0.08 mg/g for decolorized extract).[17] The high-performance
liquid chromatography (HPLC) analysis showed large differences between the two
extracts (Fig. 1), indicating that the activated carbon-filtration eliminated a large
number of components from the extract.[18] In addition, Aloe vera decolorized leaf
extract exhibited a reduction in rheological values and approximately 19%–23%
lower content of complex polysaccharides than either the gel or whole extract.[5]
2.2 Toxicity, genotoxicity, and carcinogenicity

... Toxicity of the whole leaf extract
Logarto Parra and colleagues[19] investigated the toxicity of Aloe vera (L.) Burm. F.
(Aloeaceae) extract using both in vitro and in vivo assays. Twenty-four hours fol-
lowing an acute oral exposure to Aloe vera dried leaf extract, the medium lethal
concentration (LC50) in brine shrimp was estimated as 3.59 µg/ml and the lethal
dose (LD50) in Swiss albino mice was 120.65 mg/kg. Another acute toxicity study
demonstrated a maximum tolerated dose of 100 mg/kg body weight and LD50 of
250 mg/kg, when the whole Aloe vera plant powder was extracted with 50% ethanol
and administered intraperitoneally to adult albino mice at an initial dose of 400 to

500 mg/kg.[20] In addition, Aloe vera whole-leaf material caused a dose-dependent
decrease in the viability in HeLa and HepG2 cells with half-maximal cytotoxic con-
centration (CC50) values of 413.9 and 439.0 mg/ml, respectively, following a 4-h
treatment.[21] It also caused a dose-dependent increase of apoptosis in HeLa cells at
concentrations up to 1000 mg/ml.
In a subchronic toxicity study, 88 Sprague Dawley rats were fed Aloe whole leaf
powder at doses of 2, 4, and 8 g/kg body weight (2.5%, 5%, and 10% Aloe in diet)
for 90 days.[22] All dosed rats increased defecation and rats treated with the high
doses also showed reduced food efficiency and body weight. Relative kidney weight
was significantly increased in males exposed to 8 g/kg body weight and all dosed
females. All of the exposed groups displayed a significant increase in the incidences
of pigmentation in renal tubular, mesenteric lymph nodes and lamina propria of the
colonic mucosa, and proliferation in mesenteric lymph nodes. Reproductive toxicity
was observed after a chronic oral ingestion of 100 mg/kg Aloe vera extract per day,
which is one-fifth of the pharmacologically active dose, for a period of 3 months.[23]

This was manifested by significant sperm damage, hematological changes, inflam-
mation, and mortality as compared to control animals.
As part of a 14-day drinking water study conducted by the NTP, Aloe vera non-
decolorized whole leaf extract and decolorized extract were administered to groups
of four male and four female F344/N rats and the same numbers of B6C3F1 mice at
7 weeks of age.[24] The malic acid content of 0.5%–3% Aloe vera whole and decol-
orized extract solutions was 970–5820 μg/g and 1240–7440 μg/g water, respec-
tively, and aloin A content was 70–422 μg/g and 0.8–4.5 μg/g water, respectively.
After 14 days female rats exposed to 1.5%–3% of decolorized extract displayed sig-
nificantly decreased blood urea nitrogen levels, whereas rats exposed to 3% whole
extract displayed reduced body weight, water consumption, gastrointestinal tract
transit times, and liver, heart, spleen, thymus, and kidney weight than those of con-
trols. Leukocyte and erythrocyte counts and hematocrit percentages were signifi-
cantly elevated in both male and female rats. In contrast, only a significant increase
in water consumption was observed in female mice that received 2.0% nondecol-
orized whole extract.[24]
In comparison to this study, a highly purified decolorized whole leaf Aloe vera
(L.) Burm. f. juice (total anthraquinones < 0.1 parts per million) was adminis-
tered to F344/Du rats via drinking water at concentrations up to 2% (w/v).[25]
This study was designed to compare the results obtained from other in vivo stud-
ies using whole leaf extract, specifically the NTP study reported by Boudreau and
colleagues.[24] No significant toxicological findings were observed after subchronic
exposure for 13 weeks. A similar study also showed no toxicity in F344 rats after
oral administration of a commercially available Aloe vera decolorized extract bever-
age up to 13 weeks, as evaluated by behavior, stools, weight gain, feed consumption,
organ weights, and intestinal mucosal morphologies.[26] These results suggest that
anthraquinones may be a major contributor or serve as a marker of other agent(s)
for Aloe vera-induced adverse effects.[25]
... Genotoxicity of the whole leaf extract

The genotoxicity of water extracted Aloe ferox was studied using the Bacillus sub-
tilis rec-assay in the 1980s. Aloe ferox is a palm-like succulent with many sharp
reddish-brown spines on the margins of the leaves, giving the plant name “ferox”
that means “fierce” or “war-like” in Latin. In the absence of metabolic activation,
the lengths of inhibition zones formed by 6 mg of Aloe extraction on Rec+ and
Rec− strains deviated distinctly from those of negative control samples, indicating a
positive response in the Bacillus subtilis spore rec-assay.[27] However, no genotoxic
effects were observed in the histidine reversion Ames test and DNA repair assays
using Aloe vera decolorized extract beverage at up to 21× concentrations.[26]
Recently, Aloe vera whole extract- and decolorized extract-induced cytotoxicity
and genotoxicity were evaluated in our laboratory using the mouse lymphoma assay
(MLA).[18] This study used the same test articles that were used for the 14-day stud-
ies by the NTP.[24] After a 24-h treatment, both extracts exhibited concentration-
dependent cytotoxicity and mutagenicity in the mouse lymphoma cells, with whole
extract showing a positive response at lower concentrations than the decolorized

extract. Molecular analysis of induced mutant colonies revealed that 77%–92% of
the large colonies and 100% of the small colonies from both treatments lost het-
erozygosity at the Tk locus and about half of the mutants lost heterozygosity at both
the Tk and D11Mit42 loci, thus affecting approximately 6–30 centimorgans of the
chromosome (Fig. 2). These results indicate that the primary type of damage from
both treatments was large chromosome mutations (deletions and/or mitotic recom-
bination). In addition, intracellular reactive oxygen species (ROS) levels induced
by decolorized extract was about three-fold higher than that of whole extract in
treated cells, suggesting that during the process of activated carbon filtration, some
mutagenic components were removed from whole extract and other components
with pro-oxidative or mutagenic activities, or both, might be enriched. Another
important finding in this study was that the mutagenicity of the decolorized extract
Figure . Comparison of the percentage of mutational types for all (large and small) colonies pro-
duced in cells treated with Aloe vera. Mouse lymphoma cells were treated for  h with . or  mg/ml
whole leaf extract, or  mg/ml decolorized extract. Whole extract at . or  mg/ml or decolorized
extract vs control, p < .; . mg/ml whole extract vs decolorized extract, p .;
= . mg/mlvs
 mg/ml whole extract, p = .;  mg/ml whole extract vs decolorized extract, p ..
= Data fromTable
 in [].
was detected at doses of about twice that required for whole extract-induced muta-
genicity. Since the anthraquinone content was reduced by 99% in the decolorized
extract relative to the whole extract, these results indicate that anthraquinones are
not the only mutagenic component of these mixtures and Aloe-induced genotoxicity
may not be eradicated completely by removing these chemicals from Aloe prepara-
tions.[18]
... Carcinogenicity of the whole leaf extract

NTP Technical Report 577 described clear evidence of carcinogenic activity in
F344/N rats after oral administration of Aloe vera whole leaf extract in drinking
water for two years.[28] In this study, F344/N rats and B6C3F1 mice were exposed
to 0%, 1%, 2%, or 3% (wt/wt) extract for a period of 13 weeks or 2 years. The 13-
week exposure caused increased incidences of goblet cell hyperplasia in the large
intestine of both rats and mice when compared to the control. The two-year study
demonstrated significant dose-related increases in the incidences of adenomas
and/or carcinomas of the ileocecal and cecal-colic junction, cecum, and the
ascending and transverse colon in male and female rats in the high-dose groups.[28]
Whole extract-induced large intestinal tumors in F344 rats and human colorectal
cancers shared similar changes in morphology and in molecular pathways, such as
MAPK, WNT, and TGF-β signaling.[29] In a one-year study using Wistar Hannover
rats, 4% Aloe arborescens (whole leaf powder extract) in the diet resulted in diar-
rhea, reduced body weight gain, yellowish pigmentation of ileocecal lymph nodes
and renal tubules and severe sinus dilatation of the ileocecal lymph nodes.[30] In the
subsequent two-year study, adenomas or adenocarcinomas in the cecum, colon, and
rectum were observed in the 4% male group, and adenomas were observed in the 4%
female group. The irritation of the intestinal tract may contribute to the equivocal
carcinogenic potential in the colon.[31] Due to the potential phototoxicity of herbal
products,[32] Aloe whole leaf or decolorized whole leaf creams was applied topically
in male and female SKH-1 hairless mice for one year.[33] Both products showed a
weak enhancing effect on the photocarcinogenic activity of simulated solar light,
as manifested by significantly increased histopathologically-determined squamous
cell neoplasm in some mice.
2.3. Adverse clinical effects of the whole leaf extract in humans

Topical and oral use of Aloe vera can cause skin irritation, hives, cramping, and
diarrhea to those who are allergic to other plants in the lily family, for example,
onion and tulips. Several case reports on toxicity or hypersensitivity of Aloe prod-
ucts in humans are available, but there are no published controlled toxicology stud-
ies.[34] A 35-year-old woman experienced massive intraoperative bleeding after oral
consumption of Aloe vera tablets for two weeks before the surgery for leg pain.
Compounds contained within Aloe vera can reduce the synthesis of prostaglandin,
thus inhibiting secondary aggregation of platelets. Sevoflurane, a general anesthetic,
inhibits thromboxane A(2) formation by suppressing cyclooxygenase activity. Since
both sevoflurane and Aloe vera have antiplatelet effects, the bleeding could have been
due to a possible herb–drug interaction between Aloe vera and sevoflurane.[35] A
47-year-old man developed acute oliguric renal failure and liver dysfunction after
ingestion of Cape Aloes, a previously described nephrotoxin.[36]
Hepatotoxicity is considered one of the most reported adverse effects caused by
herbal dietary supplements.[37] The first case of acute hepatitis due to the inges-
tion of Aloe vera compound was reported in 2005 in Germany.[38] Afterward,
cases of Aloe-induced toxic hepatitis were reported in Turkey,[39] United States,[40]
Argentina,[41], and Korea.[42] A total of six females and two males were admitted to
hospital for acute hepatitis after taking Aloe preparation over 3–260 weeks.[43] Their
clinical manifestation, liver biopsy, and laboratory findings supported the diagnosis
of toxic hepatitis. All eight patients showed improved conditions after discontinuing
this medication. These cases emphasize the importance of considering phytophar-
maceutical over-the-counter drugs as causative agents in hepatotoxicity.
3. Aloe vera latex or exudate
3.1. Components
Aloe vera latex or exudate is distributed within vascular bundles located between the
plant’s outer skin (rind) and the pulp. The pericyclic tubules, one of the three types
of tubular structures of vascular bundles, store and transport Aloe vera latex along
the margin of the leaf. The latex is yellow-brownish in color and has a bitter taste.
About 80 chemical constituents have been isolated by liquid chromatography in the
latex, and most of the compounds are phenolic in nature, mainly anthraquinone C-
glycosides, anthrones, and free anthraquinones.[44,45] Barbaloin, also known as aloin
A, is identified as the major constituent in the latex.[5,46] The other three main com-
ponents are isobarbaloin (aloin B), aloesin (aloeresin B), and aloeresin A.[47] The
latex also contains several other anthraquinones/anthrones and chromones includ-
ing aloe-emodin, aloeresin E, aloenin,[44] as well as some aromatic compounds, for
example, aldehydes (butanal, pentanal, etc.) and ketones (2-butanone, 2-heptanone,
etc.).[47]
3.2. Toxicity, genotoxicity, and carcinogenicity

Aloe vera latex contains a number of biologically active compounds, notably
anthraquinones. Various in vitro and in vivo assays have been performed to eval-
uate the cytotoxicity, genotoxicity, and carcinogenicity of the chemical components
contained within the latex, most especially aloe-emodin, aloin, emodin, and dan-
thron.
... Toxicity of the latex

The cytotoxicity of aloe-emodin has been investigated intensively. Aloe-emodin
induced apoptosis through various mechanisms, including a p53-dependent
pathway in T24 human bladder cancer cells[48] and G2/M cell cycle arrest in human
promyelocytic leukemia HL-60 cells.[49] During the apoptosis process induced

by aloe-emodin and emodin in human lung squamous carcinoma cells (CH27)
and human lung nonsmall cell carcinoma cells (H460), increases in cytosolic
cytochrome c, caspase-3 activation, and changes of protein kinase c (PKC) isozymes
were observed.[50] This study also demonstrated that PKC stimulation occurred
at a site downstream of caspase-3 in the emodin-mediated apoptotic pathway.
Another study demonstrated that aloe-emodine significantly inhibited proliferation
and induced apoptosis in adult human keratinocytes.[51] The impairment of ker-
atinocyte proliferation could be observed at concentrations far below the industry
standards for commercial products containing Aloe extract.
The toxicity of aloin was evaluated in human Jurkat T lymphocytes using flow
cytometry and microscopy.[52] Aloin treatment resulted in decreased cell size,
increased granularity, a block at the G2/M phase of the cell cycle, and loss of both
membrane integrity and mitochondrial membrane potential in a dose-dependent
manner, suggesting a mitochondrial-dependent pathway for aloin-induced apopto-
sis. UP780, a standardized composition of aloe chromone aloesin formulated with

an Aloe vera inner leaf fillet, showed a no-observed-adverse-effect-level in CD-1
mice with oral administration of UP780 at doses of 2 g/kg/d for 14 days or up to
1 g/kg/d for 90 days.[53]
... Genotoxicity of the latex

The genotoxicity of some anthraquinones has been confirmed in a variety of in
vitro and in vivo assay systems. A high proportion of anthraquinones was reported
to be mutagenic in a number of strains of Salmonella typhimurium, for exam-
ple, TA1537, TA1538, TA102, and TA98.[54–56] These strains are particularly sen-
sitive to frameshift mutagens. Danthron and aloe-emodin were positive in strain
TA1357 both with and without metabolic activation.[55] Aloe-emodin also induced
increased revertant colonies in strains TA 1537, TA 1538, and TA 98.[57] Muller
and colleagues[58] investigated the genotoxicity of three anthraquinones, emodin,
danthron, and aloe-emodin using the MLA, micronucleus test, and the Comet
assay. At micromolar concentrations, all three compounds induced concentration-
dependent increases in micronuclei and moderate increases in mutant frequency in
L5178Y cells. Danthron and aloe-emodin also increased DNA breaks at a concen-
tration of 50 μM in the Comet assay. The genotoxicity and mutagenicity induced
by these anthraquinones were due to the inhibition of the catalytic activity of
topoisomerase II (Topo II), with danthron being the most potent.[58,59] Emodin,
the least potent compound among the three anthraqinones, caused DNA double-
strand breaks by stabilizing Topo II-DNA cleavage complexes and by inhibiting ATP
hydrolysis of Topo II.[60] Aloe-emodin caused DNA damage in human lung carci-
noma cells through the production of ROS,[61] induced micronuclei in TK6 human
lymphoblastoid cells,[56] and chromosomal aberration in Chinese hamster ovary
cells.[57] Danthron caused DNA damage and caspase cascade-mediated apoptosis
in SNU-1 human gastric cancer cells through mitochondrial permeability transi-
tion pores and Bax-triggered pathways.[62]
An in vivo mouse Comet assay was performed on isolated kidney and colon cells
of male OF1 mice in order to demonstrate the possible organospecific genotoxicity
of aloe-emodin.[56] Increases in DNA strand breaks in both the kidney and the colon
were observed between 3 h and 6 h after two oral administrations at 500, 1000, and
2000 mg/kg body weight, suggesting an in vivo genotoxic mechanism of action.
... Carcinogenicity of the latex

Tumor promotion activities, such as stimulation of cell proliferation and enhance-
ment of malignant transformation, have been investigated in mice for 9 hydroxyan-
thraquinones (HA) including danthron, aloe-emodin, and emodin.[63] A 2 to 3-fold
increase in DNA synthesis was found in primary rat hepatocytes exposed to dan-
thron and aloe-emodin; and danthron also enhanced malignant transformation of
C3H/M2 mouse fibroblasts pretreated with N-methyl-N’-nitro-N-nitrosoguanidine
or 3-methylcholanthrene, suggesting that HA with hydroxy groups in the 1,8-
positions may have tumor-promoting activity. The carcinogenic potential of HA also
has been demonstrated in a group of 29 male ACI/N rats.[64] After 480 days feed-
ing with 1% of HA, 25 of 29 rats developed adenomas or adenocarcinomas in the
cecum or upper portion of the colon; liver neoplasms (neoplastic nodules and hep-
atocellular carcinomas) were observed in 12 rats; and benign stomach tumors were
observed in five animals. These findings strongly suggest that HA is carcinogenic in
rodents.
A two-year feeding study of emodin in male and female F344/N rats and B6C3F1
mice showed equivocal evidence of carcinogenic activity for emodin in female
F344/N rats due to a marginal increase in the incidence of Zymbal’s gland carcinoma
and in male B6C3F1 mice based on a low incidence of renal tubule neoplasms.[65]
In the rat study, diets containing 0, 280, 830, or 2500 ppm emodin (equivalent to
average daily doses of approximately 110, 320, or 1000 mg/kg to males and 120,
370, or 1100 mg/kg to females) were administered to 65 male and 65 female rats for
105 weeks. Three Zymbal’s gland carcinomas were diagnosed in female rats exposed
to 2500 ppm. In the mouse study, 60 male and female mice were fed diets contain-
ing 0–625 ppm (equivalent to average daily doses of approximately 15–70 mg/kg)
or 0–1250 ppm (equivalent to average daily doses of approximately 30–120 mg/kg)
emodin, respectively, for 105 weeks. Low incidences of renal tubule adenoma and
one carcinoma each in the 312 and 625 ppm groups were observed in exposed male
mice. No evidence of carcinogenic activity of emodin was found in female B6C3F1
mice even at the highest dose of 1250 ppm.
Evidence for aloe-emodin photocarcinogenicity was found in C3H mice after
combined treatment with ultraviolet radiation and aloe-emodin in ethanol vehi-
cle.[66] C3H/HeN mice were treated with aloe-emodin in 25% ethanol topically three
times per week for two weeks and exposed to 15 kJ/m2 UVB (280–320 nm) radia-
tion. Primary cutaneous melanin-containing tumors were diagnosed in 50%–67%
of the UV-irradiated mice given aloe-emodin in ethanol vehicle and in 20%–30% of
the mice treated with a combination of UV radiation and ethanol vehicle, whereas
no skin tumors were induced by aloe-emodin alone in the absence of UV radiation.
3.3. Adverse clinical effects of the latex in humans

The purgative effect of Aloe latex has long been recognized and has been used empir-
ically to relieve constipation. The earliest medical writer to record the therapeutic
use of Aloe is Dioscorides, a Greek physician of the first century A.D.[67] Subse-
quently, Aloe latex was used widely in herbal laxative preparations in many coun-
tries. Thus, a number of adverse effects resulting from ingestion of latex have been
reported in clinical studies. Prolonged use was associated with electrolyte imbalance
due to diarrhea, abdominal pain, vomiting, hypokalemia, pseudomelanosis coli, and
the development of a cathartic colon—the colon becomes atonic and dilated. Long-
term use of anthranoid laxatives might be correlated with the risk of developing
colon cancer.[68]
A case of Aloe-induced Henoch-Schonlein purpura, an idiopathic vasculitis of
the small vessels, was reported. A 52-year-old male patient from Pakistan presented
severe arthralgia, palpable purpura, and abdominal pain ten days after taking some
juice extracted from four to five leaflets of Aloe vera. Twenty-four hours after the
juice consumption, the man started to have rash on his legs and a mild arthralgia of
the ankle. His symptoms worsened in the following days, and he developed diffuse,
colicky, abdominal pain. Marked segmental necrosis and crescent formation were
demonstrated by a renal biopsy. The renal dysfunction and nephritis were consid-
ered to be a consequence of large doses of Aloe.[69]
A 74-year-old female presented with an impressive deep black pigmentation of
the whole colon after chronic use of anthraquinone laxatives over many decades.
Various adenomas, which were classified as precancerous lesions, were detected,
but no colorectal carcinoma was found.[70] An 18-year-old Caucasian girl, who was
treated with a combination laxative containing 5 ml danthron orally at night to
ameliorate constipation from 14 months old to 5–6 years old, presented a small
bowel leiomyosarcoma with widespread dissemination.[71] Although one case can-
not prove a causative association between danthron and the risk of developing bowel
cancer, the authors concluded that prolonged oral exposure to the laxative should be
avoided in early childhood. In addition, pregnant women were advised not to take
Aloe latex because its cathartic property might result in stimulating uterine contrac-
tions, thereby increasing the risk for premature labor or miscarriage. Also, nursing
mothers should not take laxatives because of the possibility of anthraquinones caus-
ing diarrhea in the infants.[3]
4. Aloe vera gel
4.1. Components
Aloe vera gel is a transparent mucilaginous jelly-like substance contained in the
parenchymatous cells of fresh Aloe vera leaf pulp, with a gel yield of approximately
70% (70 g gel/100 g pulp) from the pulp by mechanical extrusion.[72] The gel has
very high water content (99%–99.5%), with the remaining soluble solids making
up 0.5%–1%,[73] and a range of gel acidity (pH) of 4.4–4.7.[74] On a dry matter

basis, the chemical constituents consist of 35% dietary fibers (nonstarch polysac-
charides + lignin), 27% soluble sugars, 24% ash, and a minor fraction of lipids, pro-
teins, enzymes, and mineral elements.[7,72] The alcohol insoluble residues obtained
from Aloe vera gel lyophilized fractions have a high content of carbohydrates (72%)
including mannose, glucose, and uronic acids. Linear chains of β-1-4-linked man-
nose and glucose molecules compose the primary polysaccharides at a ratio of
1∼22:1 in the gel.[6,7,75–77] Most investigators agree that acemannan, an acetylated
glucomannan, makes up the major active component of the mucilaginous Aloe vera
gel,[72] while others report pectic substance as the main polysaccharide.[73] The dis-
crepancies are considered to be a result of differences in the species, seasons of the
year, geographical locations, and the gel extraction process.
4.2. Toxicity, genotoxicity, and carcinogenicity

The toxic effects of Aloe vera gel have been reported only in a few studies. There
is diversity in the results of the observed toxic effects which may be largely due to
the differences in the gel contents that are greatly influenced by a variety of factors
including seasons, locations, irrigation, harvest time, and, most importantly, the lack
of standardization of the gel preparations.
... Toxicity of the gel

The cytotoxicity of Aloe vera gel has been confirmed in monolayers of chicken
fibroblasts based on the observations of disrupted intercellular junctions and the
formation of cell-free gaps in the monolayers after treatment.[78] The cell injury
assay was conducted using three fractions isolated from the Aloe barbadensis leaves,
native gel (mucilaginous parenchymous tissue scraped from Aloe leaves), purified
gel (the nondialyzable fraction of the native gel), and the low molecular weight frac-
tion (LMWF, the dialyzable material). A 1:10 dilution of native gel and the LMWF
promoted similar cell injuries, while the purified gel behaved like the control at the
same dilution. These severe cellular damages were distinct enough to be detected
under a microscope. Therefore, it was proposed that the toxicity was mainly caused
by the LMWF from the gel since the beneficial characteristics were suggested to
result from the high molecular weight components.[78] Following a 4-hour treat-
ment, an Aloe vera dehydrated gel material induced dose-dependent cytotoxicity in
HeLa cells, with a CC50 value of 269.3 mg/ml.[21]
Aloe vera gel was administered in drinking water to groups of four male and four
female F344/N rats in a 14-day study conducted by the NTP.[28] The gel quality was
monitored by the content of malic acid and aloin A (barbaloin). Drinking water
solutions of 0.5%–3% Aloe vera gel contained 1060–6360 μg malic acid/g water, and
5.6–33.3 μg aloin A/g water. After the 14-day exposure, dose-related increases in
urine glucose levels in female rats and dose-related decreasing trends in serum levels
of triglycerides, cholesterol, and albumin were observed at concentrations of 1.5%
or greater in female rats and of 3.0% in male rats. When adult male Wistar rats were
orally administered with Aloe vera gel extract solution (150 and 300 mg/kg/day)
for 8 weeks, the weight of testes, serum testosterone, sperm count, and sperm fer-
tility were significantly decreased compared to the control rats.[79] In another in
vivo study using a commercial stabilized Aloe vera gel consumed as a beverage, no
changes were found in feed consumption, body weight gain, and serum chemistry
tests following a 13-week subchronic exposure in B6C3F1 mice.[80]
After 5.5 months ingestion of crude skinned Aloe filet to male F344 rats, no
adverse effect was observed on body weight gain, food intake, gastrointestinal transit
time, or gross pathology at dietary concentrations of 1% or 10% (corresponding to
doses of Aloe vera gel of ∼0.33 and 3.3 g/kg bw/day).[16,81] Life-long ingestion of low
dose (1%) Aloe vera filet caused no obvious harmful effects or deleterious changes
in the rat.[82]
... Genotoxicity of the gel

Studies on the biological effects of Aloe vera pulp extract on Escherichia coli-deficient
repair mutants and plasmid DNA revealed genotoxic properties of the gel, but
not cytotoxicity because of the poor permeability through the cell membrane. The
agarose gel electrophoresis assay showed that Aloe vera pulp extract produced dose-
dependent single-strand breaks in the plasmid DNA.[83] In vitro and in vivo safety
studies using a high-purity Aloe vera inner leaf fillet preparation demonstrated that
the gel was nonmutagenic in the Ames test, the chromosomal aberration test, and
the in vivo bone marrow micronucleus test, following oral administration at doses
up to 5 g/kg bw/day to rats for 90 days[84] Similarly, a commercial gel juice did not
induce a significant increase in SOS DNA repair in Escherichia coli or mutagenesis
in Salmonella TA100[80]
... Carcinogenicity of the gel

No carcinogenicity data are available for Aloe gel.
4.3. Adverse clinical effects of the gel in humans

Aloe gels were first used clinically in the 1930s for the treatment of radiation
burns.[34] Afterward, several clinical trials of Aloe vera gel have been carried out in
the treatment of burn wounds,[85] oral lichen planus,[86] hyperlipidemic type 2 dia-
betic patients,[87] and recurrent aphthous stomatitis.[88] Only some minor adverse
effects were reported in these studies, such as discomfort, pain, and the development
of hypersensitive reactions. However, generalized eczematous and papular dermati-
tis were found in a male patient in response to the oral and topical use of the Aloe
vera gel.[89] Pruriginous erythema was observed on the legs and eyelids of a 72-year-
old woman after applying self-made Aloe vera leaf juice over the legs.[90] A very slow
recovery from the dermatitis induced by Aloe vera preparations was reported in four
cases after dermabrasion and chemical peel.[91] No severe adverse effects or carcino-
genicity have been reported from using Aloe vera gel.
5. Perspectives
More than 300 million people worldwide consume dietary supplements and herbal
plants, and about one-half of Americans use them regularly.[92] Dietary or herbal
supplement products are expected to be safe, effective, and of appropriate quality.
However, the complex chemical nature of dietary supplements makes it difficult to
evaluate their efficacy and safety. Herbal products often exhibit great variability in
quality because of some issues including authentication, adulteration and substitu-
tion, and factors during growth, harvest, and postharvest processing.[93] Authentica-
tion of plant species used for preparation of herbal dietary supplements is important
for safety assurance. Besides traditional approaches, the use of molecular/genetic
profiling in identification of specific molecular changes (fingerprints) and in unveil-
ing signature indicative of exposures remains a promising yet still largely unexplored
approach.[94,95]
The reported adverse effects have raised concerns of public health risks regard-
ing the concentration, composition, and individual contaminants of dietary supple-
ments. Herbal dietary supplements and other herbal products have been recognized
as the common causes of drug-induced liver injury.[96] A recent report indicates
that dietary/herbal supplements are implicated in 19% of drug-induced acute liver
failure cases,[97] because consumers often purchase these products online without
the supervision of a health care provider and are not aware of drug–herb interac-
tions and appropriate warnings. A total of 1179 English-language, herbal product-
related websites (including retail and nonretail websites) were examined and only
∼10% of them recommended consultation with a health care professional. In addi-
tion, only about 8% of internet retailers provided information on potential adverse
effects, drug interactions, and other basic safety precautions; and less than 3% cited
scientific references to their claims.[98]
Aloe plant contains multiple constituents with potential beneficial and toxico-
logical activities. Three distinct preparations derived from Aloe vera (i.e., the whole
leaf extract, Aloe vera gel, and Aloe vera latex) have been used as topical and oral
therapeutic remedies. The gel is primarily used topically for wounds and skin prob-
lems, as well as taken orally for the treatment of gastrointestinal ulcers and dia-
betes.[9] The latex is regulated as a drug by the FDA to relieve constipation and the
whole leaf extract may possess antibacterial/viral and anticancer activities.[5] Aloe
vera appears to be safe when used as a flavoring in foods[16]; and the polysaccharide
material derived from the inner gel is noncytotoxic as evaluated by the Cosmetic
Ingredient Review Expert Panel.[3] However, due to the cytotoxicity, mutagenicity,
and carcinogenicity of anthraquinones, it is crucial to monitor the content of these
phenolic compounds in Aloe vera whole leaf extract and latex.[5,24] The International
Aloe Science Council standard suggests that the maximum allowable aloin content
in Aloe-derived material for oral consumption is less than 10 ppm (parts per mil-
lion); for nonmedical use the recommended limit is 50 ppm or lower.[3,99]
According to Multinational Integrated Data Analysis conducted by IMS Health
(Danbury, CT), the estimated global sales of Aloe products have reached US
$351 million.[16] Due to the increased popularity and utilization of Aloe plant, in-
depth studies are needed to investigate the adverse effects, conventional drug inter-
actions, and the possible toxic and carcinogenic effects of Aloe preparations, espe-
cially after long-term use of these products.
Acknowledgments
We thank Drs. Robert H. Heflich, Page B. McKinzie, and Vasily N. Dobrovolsky for their helpful
suggestions and comments. The information in these materials is not a formal dissemination of
information by the US Food and Drug Administration and does not represent agency position
or policy.
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Aloe Vera – review toksisitas dan efek klinis yang merugikan
Abstrak
Tanaman Aloe digunakan sebagai suplemen makanan dalam berbagai makanan dan
sebagai bahan dalam produk kosmetik. Paparan manusia yang meluas dan potensi
kegiatan beracun dan karsinogenik meningkatkan masalah keamanan. Analisis kimia
mengungkapkan bahwa tanaman Aloe mengandung berbagai polisakarida dan bahan
kimia fenolik, terutama anthraquinones. Menelan persiapan Aloe adalah Asso-Venus
dengan diare, hipokalemia, pseudomelanosis Koli, gagal ginjal, serta fototoksisitas dan
reaksi hipersensitif. Baru-baru ini, Aloe Vera seluruh ekstrak daun menunjukkan bukti
yang jelas dari aktivitas karsinogenik pada tikus, dan diklasifikasikan oleh badan
internasional untuk penelitian kanker sebagai karsinogen manusia mungkin (kelompok
2B). Tinjauan ini menyajikan informasi terbaru tentang efek Toksikologi, termasuk
cytotoxicity, genotoxicity, karsinogenisitas, dan efek klinis yang merugikan AloeVera
seluruh daun ekstrak, gel, dan lateks.
1. Pendahuluan
Penggunaan produk herbal telah berkembang pesat di masyarakat umum. Dalam
2007, survei wawancara Kesehatan Nasional melaporkan bahwa sekitar 40% dari
Amerika, termasuk orang dewasa dan anak, digunakan pelengkap dan pengobatan
alternatif sebagai terapi alternatif dalam 12 bulan terakhir. [1] tentang US
$14.800.000.000 dihabiskan pada pembelian nonvitamin, produk alami nonmineral,
yang menyumbang 44% dari semua biaya Out-of-saku untuk pelengkap dan
pengobatan alternatif. [2] Aloe telah menikmati sejarah panjang menyediakan
segudang manfaat kesehatan, dan merupakan salah satu obat herbal yang paling
sering digunakan digunakan di seluruh dunia. Ada lebih dari 400 spesies Aloe, tetapi
spesies yang paling populer dan banyak digunakan adalah Aloe barbadensis Miller
(juga disebut Aloe Vera Linne, biasanya disebut Aloe Vera). Aloe berasal dari kata
Arab alloeh yang berarti "zat pahit dan mengkilap," dan Vera dari kata Latin untuk
"kebenaran." Spesies lain yang digunakan dalam kesehatan dan obat-obatan
termasuk tetapi tidak terbatas pada Aloe arborescens Miller (anggota keluarga
asphodelacea), Aloe perryi Baker, Aloe andongensis, dan Aloe ferox.
Aloe Vera, sebuah genus dalam Famili Liliaceae, adalah Stemless atau sangat kemeja
yang bertangkai abadi lezat atau xerophyte dengan daun memanjang dan memuncak
di mana sejumlah besar air disimpan dalam jaringan. [5] daun berdaging hijau berkisar
pada ketinggian dari beberapa sentimeter hingga 2 – 3 meter atau lebih dan memiliki
tiga lapisan yang dapat dikenali. Lapisan luar adalah kutikula tebal atau kulit akuntansi
untuk sekitar 20% – 30% oleh berat seluruh daun tanaman. Ini terdiri dari hingga 18
lapisan sel diselingi dengan kloroplasts di mana karbohidrat, lemak, dan protein
disintesis. Pulp daun luar, lapisan tipis, mucilaginous tepat di bawah dan berdekatan
dengan kulit tebal, mengandung bundel vaskular bertindak sebagai sistem transportasi
untuk tanaman. Tiga jenis struktur Tubular menyusun bundel vaskular: xylem, yang
bergerak air dan mineral dari akar ke daun; Phloem, yang mengambil disintesis
mineral ke akar; dan tubulus perisiklik, yang menyimpan dan mengangkut lateks
kuning pahit (sering disebut sebagai Aloe getah) di sepanjang margin daun. Jumlah
bundel ini bervariasi berdasarkan ukuran daun. [6] pulp daun bagian dalam
membentuk mayoritas tanaman dengan volume, dan terdiri dari sel parenchymal
terberdinding besar yang mengandung Aloe Vera gel, sinonim untuk daun batin, fillet
daun batin, atau fillet.
Aloe mengandung bahan farmakologically aktif yang terkait dengan beragam kegiatan
biologis termasuk fungisida, antivirus, antibakteri, anti-inflamasi, antimikroba,
pencahar, imunomodulasi, dan efek antikanker. [3] lidah buaya, yang dikenal sebagai
"tanaman keabadian" di awal Mesir, telah digunakan sebagai obat tradisional dalam
bahasa Arab, Cina, Mesir, Yunani, India, Jepang, Korea, dan budaya Romawi [7, 8]
selama lebih dari 2000 tahun untuk secara empiris memperlakukan daftar luas
gangguan dan penyakit, seperti masalah kulit (luka, x-ray dan Radium luka bakar, dan
psoriasis), sembelit, ulkus eksternal dan internal, hiperlipidemia, diabetes, dan lupus
eritematosus.
[9 – 12] Karena banyaknya efek menguntungkan yang diakui, Aloe Vera produksi telah
berkembang industri untuk membuat obat pencahar, kosmetik, dan fungsional
makanan, seperti wajah dan krim tangan, Yayasan, pembersih, lipstik, berjemur lotion,
shampo dan rambut tonics, persiapan mencukur, mandi AIDS, makeup dan
wewangian persiapan, bayi lotion dan tisu, yoghurt, minuman, kapsul, dan tablet.
Dalam rangka untuk menunjukkan saat ini farmakologis dan/atau Toksikologi status
penelitian pada Aloe, kami melakukan pencarian literatur di PubMed menggunakan
"Aloe" dan nama negara tertentu sebagai kata kunci (Tabel 1). Sebanyak 1895 dan
975 publikasi diidentifikasi ketika menggunakan "Aloe" sebagai kata kunci dalam
semua bidang tidak penulis dan MeSH istilah database, masing-masing. Lebih dari
setengah (51% – 60%) dari studi ini dilakukan di 10 negara teratas (Tabel 1), dan
sekitar sepertiga dari mereka adalah dari lima negara Asia, termasuk Cina, India,
Jepang, Korea, dan Iran. Namun, hanya sekitar 8% dari artikel ini diselidiki Aloe yang
berhubungan dengan toksisitas in vitro dan in vivo.
Meskipun Aloe Vera telah lama dianggap sebagai bahan makanan fungsional yang
aman yang dapat digunakan secara lisan dan topikal, [13] pada banyak kesempatan
itu belum aman seperti yang biasa dipikirkan. Baru-baru ini, efek samping yang
dilaporkan pada manusia dan toksisitas, genotoxicity, dan karsinogenicity dalam studi
in vitro dan in vivo menimbulkan pertanyaan apakah komponen dalam Aloe Vera
mungkin memiliki tumor mempromosikan kegiatan pada manusia. Karena paparan
manusia yang luas dan keprihatinan bahwa beberapa komponen dapat menyebabkan
kanker, di 1998 National Cancer Institute dinominasikan Aloe Vera sebagai kandidat
prioritas tinggi untuk studi karsinogenisitas di bawah program Toksikologi Nasional
(NTP). Pada 2002, Amerika Serikat administrasi makanan dan obat (FDA)
mengeluarkan aturan akhir yang menyatakan bahwa penggunaan Aloe sebagai obat
pencahar nonprescription tidak lagi umumnya diakui sebagai aman dan efektif. [14]
baru-baru ini, Aloe Vera ekstrak seluruh daun telah diklasifikasikan oleh badan
internasional untuk penelitian kanker sebagai karsinogen manusia mungkin (kelompok
2B), bersama dengan produk alami lainnya seperti Ginkgo Biloba ekstrak dan kava
ekstrak. [15, 16]
Aloe Vera ekstrak seluruh daun, serta dua komponen utama (gel dan lateks atau
ekkurma) dari daun, telah digunakan untuk berbagai alasan dalam pengobatan tradi-
tional. Umumnya, gel digunakan secara topikal untuk menenangkan luka, luka bakar,
dan iritasi kulit, dan lateks diakui memiliki efek katarsis. Namun demikian, masih ada
beberapa kebingungan seputar seluruh daun ekstrak, gel, dan lateks. Mengingat
bahwa sifat bermanfaat Aloe Vera telah dibahas secara komprehensif dan bahwa gel
dan lateks memiliki komponen yang berbeda dan tujuan medis, [5] dalam artikel ini,
ekstrak daun seluruh, gel, dan keracunan lateks yang terkait, genotoxicity, dan
karsinogenisitas baik secara in vitro dan in vivo ditinjau, dan efek klinis yang
merugikan pada manusia juga diringkas.
2. Aloe Vera ekstrak seluruh daun
2,1 komponen
Ekstrak seluruh daun Aloe Vera, termasuk gel dan lateks, mengandung lebih dari 200
zat kimia. [4] daun Aloe mentah terdiri dari sekitar 98,5% air, bahan padat yang tersisa
berisi berbagai senyawa termasuk nutrisi (misalnya, karbohidrat, asam amino, vitamin,
dan mineral) dan non nutrisi (misalnya, asam organik, lignin, senyawa fenolik,
anthraquinones, dan phytosterols). Komposisi kimia dan potensi berbagai konstituen
dipengaruhi oleh banyak faktor, seperti spesies/subspesies, iklim, tanah dan irigasi,
metode budidaya, panen, pengolahan ekstraksi, dan kondisi penyimpanan.
Untuk menentukan apakah kehadiran lateks mengubah sifat fisik dan kimia di seluruh
daun ekstrak, Aloe Vera seluruh daun yang dipewarnaan telah dipelajari untuk
toksisitas dan karsinogenisitas potensial. Ekstrak decolorized disiapkan oleh
carbonadsorpsi diaktifkan dari seluruh ekstrak daun (1%, w/w) untuk menghapus
bagian lateks tanaman, terutama anthraquinones, komponen memberikan Aloe Vera
sifat pencahar nya. Namun, beberapa polisakarida berat molekul tinggi dari gel lidah
daun batin juga dapat dihilangkan dengan penyerapan arang. Analisis kimia
mengungkapkan bahwa konsentrasi aloin, prinsip anthraquinone dari Aloe Vera lateks,
berbeda bya faktor 100 dalam ekstrak tanpa filter dan disaring (8 mg/g untuk seluruh
ekstrak dan 0,08 mg/g untuk ekstrak decolorized). [17] analisis kromatografi cair
berkinerja tinggi (HPLC) menunjukkan perbedaan yang besar antara kedua ekstrak
tersebut (Gbr. 1), yang mengindikasikan bahwa filter karisator aktif menghilangkan
sejumlah besar komponen dari ekstrak. [18] Selain itu, ekstrak Aloe Vera decolorized
daun dipamerkan pengurangan nilai reologi dan sekitar 19% – 23% menurunkan
kandungan polisakarida kompleks daripada gel atau seluruh ekstrak.
2,2 toksisitas, genototoksisitas, dan karsinogenisitas
. . . toksisitas ekstrak daun seluruh
Logarto Parra dan rekan-rekannya [19] menyelidiki toksisitas lidah buaya (L.) Burm. F.
(Aloeaceae) ekstrak menggunakan baik in vitro dan in vivo assays. Dua puluh empat
jam fol untuk paparan lisan akut ekstrak daun kering Aloe Vera, media konsentrasi
mematikan (LC50) dalam udang air garam diperkirakan sebagai 3,59 μg/ml dan dosis
mematikan (LD50) di Swiss albino tikus adalah 120,65 mg/kg. Studi toksisitas akut lain
menunjukkan dosis maksimum ditoleransi 100 mg/kg berat badan dan LD50 250
mg/kg, ketika Aloe Vera seluruh tanaman bubuk diekstrak dengan 50% etanol dan
diberikan intraperitoneally untuk dewasa albino tikus pada dosis awal 400 untuk 500
mg/kg. [20] Selain itu, bahan daun seluruh Aloe Vera menyebabkan penurunan dosis
tergantung pada kelangsungan hidup di HeLa dan sel HepG2 dengan setengah
konsentrasi sitotoksik maksimal (CC50) nilai 413,9 dan 439,0 mg/mL, masing-masing,
setelah pengobatan 4-h. [21] Hal ini juga menyebabkan peningkatan tergantung dosis
apoptosis di sel HeLa pada konsentrasi hingga 1000 mg/ml.
Dalam studi toksisitas subkronis, 88 Sprague Dawley tikus diberi makan Aloe seluruh
daun bubuk pada dosis 2, 4, dan 8 g/kg berat badan (2,5%, 5%, dan 10% Aloe dalam
diet) untuk 90 hari. [22] semua tikus tertutup meningkat buang air besar dan tikus
diperlakukan dengan dosis tinggi juga menunjukkan mengurangi efisiensi makanan
dan berat badan. Berat ginjal relatif meningkat secara signifikan pada pria terpapar 8
g/kg berat badan dan semua betina tertutup. Semua kelompok yang terpapar
menunjukkan peningkatan yang signifikan dalam insiden pigmentasi di tabung ginjal,
kelenjar getah bening mesenterik dan lamina propria dari mukosa kolon, dan
proliferasi di kelenjar getah bening mesenterik. Toksisitas reproduksi diamati setelah
konsumsi oral kronis 100 mg/kg Aloe Vera ekstrak per hari, yang merupakan
seperlima dari dosis Farmakologi aktif, untuk jangka waktu 3 bulan. [23] ini dinyatakan
oleh kerusakan sperma yang signifikan, perubahan Hematologi, peradangan, dan
kematian dibandingkan dengan hewan kontrol.
Sebagai bagian dari 14 hari studi air minum yang dilakukan oleh NTP, Aloe Vera tidak
decolorized ekstrak seluruh daun dan ekstrak decolorized diberikan kepada kelompok
empat pria dan empat perempuan F344/N tikus dan jumlah yang sama B6C3F1 tikus
pada 7 minggu usia. [24] kandungan asam Malat 0,5% – 3% Aloe Vera keseluruhan
dan decol-orized ekstrak solusi adalah 970 – 5820 μg/g dan 1240 – 7440 μg/g air,
respec-tively, dan aloin A konten adalah 70 – 422 μg/g dan 0.8 – 4.5 μg/g air, masing-
masing. Setelah 14 hari tikus betina terpapar 1.5% – 3% ekstrak decolorized
ditampilkan secara signifikan menurun kadar nitrogen urea darah, sedangkan tikus
terpapar 3% seluruh ekstrak ditampilkan mengurangi berat badan, konsumsi air, waktu
transit saluran pencernaan, dan hati, jantung, limpa, timus, dan berat ginjal daripada
kontrol. Leukosit dan jumlah eritrosit dan hematokrit persentase secara signifikan
meningkat pada tikus jantan dan betina. Sebaliknya, hanya peningkatan yang
signifikan dalam konsumsi air diamati pada wanita tikus yang menerima 2,0%
nondecolorized ekstrak seluruh.
Dibandingkan dengan studi ini, yang sangat dimurnikan decolorized seluruh daun Aloe
Vera (L.) Burm. f. Juice (Total anthraquinones < 0,1 bagian per juta) diberikan kepada
F344/du tikus melalui air minum pada konsentrasi hingga 2% (w/v). [25] penelitian ini
dirancang untuk membandingkan hasil yang Diperoleh dari studi in vivo lainnya
dengan menggunakan ekstrak daun utuh, khususnya studi NTP yang dilaporkan oleh
Boudreau dan kolega. [24] tidak ada temuan Toksikologi yang signifikan diamati
setelah paparan subkronis selama 13 minggu. Sebuah studi serupa juga menunjukkan
tidak ada toksisitas pada F344 tikus setelah pemberian oral ekstrak Aloe Vera yang
dijual secara komersial decolorized minuman hingga 13 minggu, seperti yang
dievaluasi oleh perilaku, bangku, berat badan, konsumsi pakan, bobot organ, dan
morfologi usus mukosa. [26] hasil ini menunjukkan bahwa anthraquinones mungkin
kontributor utama atau melayani sebagai penanda agen lain (s) untuk Aloe Vera
disebabkan efek samping.
. . . genotoxicity dari seluruh daun ekstrak
Genototoksisitas air diekstrak Aloe terung dipelajari menggunakan Bacillus subtilis
rekassay di tahun 1980-an. Aloe terung adalah telapak-seperti lezat dengan banyak
tajam coklat kemerahan-duri pada margin daun, memberikan nama tanaman "terung"
yang berarti "sengit" atau "perang-seperti" dalam bahasa Latin. Dengan tidak adanya
aktivasi metabolik, panjang zona penghambatan dibentuk oleh 6 mg ekstraksi Aloe
pada REC + dan REC-strain menyimpang dari yang jelas dari kontrol negatif sampel,
menunjukkan tanggapan positif di Bacillus subtilis spora REC-assay. [27] Namun,
tidak ada efek genotoksik diamati dalam Reversi histidine Ames uji dan perbaikan
DNA tes menggunakan Aloe Vera decolorized ekstrak minuman pada hingga 21 ×
konsentrasi. 26
Baru-baru ini, Aloe Vera seluruh ekstrak dan decolorized diinduksi ekstrak cytotoxicity
dan genotoxicity dievaluasi di laboratorium kami menggunakan alat tes limfoma tikus
(MLA). [18] studi ini menggunakan artikel uji yang sama yang digunakan untuk studi
14 hari oleh NTP. [24] setelah 24-h pengobatan, kedua ekstrak dipamerkan
konsentrasi tergantung cytotoxicity dan mutagenicity dalam sel limfoma mouse,
dengan seluruh ekstrak menunjukkan respon positif pada konsentrasi yang lebih
rendah daripada ekstrak decolorized. Analisis molekuler diinduksi koloni mutan
mengungkapkan bahwa 77%-92% dari koloni besar dan 100% dari koloni kecil dari
kedua perawatan yang hilang heterozigositas di lokus TK dan sekitar setengah dari
para mutan kehilangan heterozigositas pada kedua TK dan D11Mit42 loci, sehingga
mempengaruhi sekitar 6 – 30 centimorgans dari kromosom (Gbr. 2). Hasil ini
menunjukkan bahwa jenis utama kerusakan dari kedua perawatan adalah mutasi
kromosom besar (penghapusan dan/atau rekombinasi mitosis). Selain itu, spesies
oksigen reaktif intraseluler (ROS) tingkat yang disebabkan oleh ekstrak decolorized
adalah sekitar tiga kali lipat lebih tinggi daripada seluruh ekstrak dalam sel diobati,
menunjukkan bahwa selama proses penyaringan karbon aktif, beberapa komponen
mutagenik dihapus dari seluruh ekstrak dan komponen lainnya dengan kegiatan
prooksidatif atau mutagenik, atau keduanya, mungkin diperkaya. Temuan penting
lainnya dalam studi ini adalah bahwa mutagenisitas ekstrak decolorized terdeteksi
pada dosis sekitar dua kali yang diperlukan untuk keseluruhan mutagenicity diinduksi
ekstrak. Karena kandungan anthraquinone berkurang 99% pada ekstrak decolorized
relatif terhadap seluruh ekstrak, hasil ini menunjukkan bahwa anthraquinones bukan
satu-satunya komponen mutagenik dari campuran ini dan Aloe diinduksi genotoxicity
mungkin tidak dapat diberantas sepenuhnya dengan menghilangkan bahan kimia ini
dari prepara-tions Aloe. 18
. . . karsinogenicity dari ekstrak daun seluruh

Laporan teknis NTP 577 dijelaskan bukti yang jelas dari aktivitas karsinogenik di
F344/N tikus setelah pemberian oral Aloe Vera seluruh ekstrak daun dalam air minum
selama dua tahun. [28] dalam studi ini, F344/N tikus dan B6C3F1 tikus yang terpapar
ke 0%, 1%, 2%, atau 3% (WT/WT) ekstrak untuk jangka waktu 13 minggu atau 2
tahun. Paparan 13-minggu menyebabkan peningkatan insiden hiperplasia sel Piala di
usus besar dari kedua tikus dan tikus bila dibandingkan dengan kontrol. Studi dua
tahun menunjukkan peningkatan dosis yang signifikan terkait dalam insiden adenoma
dan/atau karsinoma dari persimpangan ileocecal dan cecalcolic, cecum, dan titik dua
yang menaik dan melintang pada tikus jantan dan betina dalam kelompok dosis tinggi.
[28] seluruh ekstrak yang disebabkan tumor usus besar pada F344 tikus dan kanker
kolorektal manusia berbagi perubahan yang sama dalam morfologi dan dalam jalur
molekuler, seperti MAPK, WNT, dan TGF-β signaling. [29] dalam satu tahun studi
menggunakan Wistar Hannover tikus, 4% Aloe arborescens (ekstrak seluruh daun
bubuk) dalam diet mengakibatkan diare, mengurangi berat badan, pigmentasi
kekuningan dari kelenjar getah bening ileocecal dan tubulus ginjal dan berat sinus
dilatasi kelenjar getah bening ileocecal. [30] dalam studi dua tahun berikutnya,
adenoma atau adenocarcinoma di sekum, usus besar, dan rektum diamati dalam
kelompok pria 4%, dan adenoma diamati dalam kelompok wanita 4%. Iritasi pada
saluran usus dapat berkontribusi pada potensi karsinogenik samar di usus besar. [31]
karena potensi fototoksisitas produk herbal, [32] Aloe seluruh daun atau decolorized
krim seluruh daun ini diterapkan secara topikal pada pria dan wanita SKH-1 tikus
berbulu selama satu tahun. [33] kedua produk menunjukkan efek meningkatkan lemah
pada aktivitas fotokarsinogenik simulasi cahaya matahari, seperti yang
dimanifestasikan oleh secara signifikan peningkatan Histopatologi ditentukan sel
skuamosa Neoplasma di beberapa tikus.
konsentrasi. 26

konsentrasi. 26

konsentrasi. 26

Efek klinis yang merugikan dari seluruh ekstrak daun pada manusia
Penggunaan topikal dan oral lidah buaya dapat menyebabkan iritasi kulit, gatal-kejang,
kram, dan diare bagi mereka yang alergi terhadap tanaman lain dalam keluarga Lily,
misalnya, bawang dan Tulip. Beberapa kasus laporan pada toksisitas atau
hipersensitivitas dari produk Aloe pada manusia yang tersedia, tetapi tidak ada yang
diterbitkan studi Toksikologi terkontrol. [34] seorang wanita berusia 35 tahun
mengalami pendarahan intraoperatif besar-besaran setelah konsumsi oral Aloe Vera
tablet selama dua minggu sebelum operasi untuk nyeri kaki. Senyawa yang
terkandung dalam Aloe Vera dapat mengurangi sintesis prostaglandin, sehingga
menghambat agregasi sekunder trombosit. Sevoflurane, anestesi umum, menghambat
tromboksan a (2) pembentukan dengan menekan aktivitas siklooksigenase. Karena
kedua sevoflurane dan Aloe Vera memiliki efek antiplatelet, perdarahan bisa saja
karena ramuan mungkin-interaksi obat antara Aloe Vera dan sevoflurane. [35] seorang
pria berusia 47 tahun mengembangkan gagal ginjal oligurik akut dan disfungsi hati
setelah menelan Cape ALOES, yang sebelumnya dijelaskan nephrotoxin. [36]
Hepatotoksisitas dianggap salah satu efek samping yang paling dilaporkan
disebabkan oleh suplemen diet herbal. [37] kasus pertama dari hepatitis akut
disebabkan oleh pinggiran Aloe Vera senyawa dilaporkan di 2005 di Jerman. [38]
setelah itu, kasus hepatitis beracun yang diinduksi Aloe dilaporkan di Turki, [39]
Amerika Serikat, [40] Argentina, [41], dan Korea. [42] sebanyak enam perempuan dan
dua jantan dirawat di rumah sakit untuk hepatitis akut setelah mengambil lidah
persiapan lebih dari 3 – 260 minggu. [43] manifestasi klinis mereka, biopsi hati, dan
temuan laboratorium mendukung diagnosis hepatitis beracun. Semua delapan pasien
menunjukkan kondisi membaik setelah penghentian obat ini. Kasus ini menekankan
pentingnya mempertimbangkan phytophar maceutical atas counter obat sebagai agen
kausatif dalam hepatotoksisitas.
3. Aloe Vera lateks atau ekdate
3,1. komponen
Lidah buaya lateks atau ekikuidasi didistribusikan dalam bundel pembuluh darah yang
terletak di antara kulit luar tanaman (rind) dan pulp. Tubulus perikasclic, salah satu
dari tiga jenis struktur Tubular bundel pembuluh darah, menyimpan dan mengangkut
Aloe Vera lateks di sepanjang margin daun. Lateks berwarna kuning kecoklatan dan
memiliki rasa pahit. Tentang 80 konstituen kimia telah terisolasi oleh kromatografi cair
dalam lateks, dan sebagian besar senyawa yang fenolik di alam, terutama
anthraquinone C-glikosida, anthrones, dan bebas anthraquinones. [44, 45] barbaloin,
juga dikenal sebagai aloin A, diidentifikasi sebagai konstituen utama dalam lateks. [5,
46] tiga komponen utama lainnya adalah isobarbaloin (aloin B), aloesin (aloeresin B),
dan aloeresin A. [47] lateks juga mengandung beberapa anthraquinones/anthrones
dan kromones lainnya, termasuk Aloe-Emodin, aloeresin E, aloenin, [44] serta
beberapa senyawa aromatik, misalnya, Aldehida (butanal, pentanal, dll.) dan keton (2-
butanone, 2-heptanone, dll.). [47]
3,2. toksisitas, genotoxicity, dan karsinogenisitas

Aloe Vera Latex mengandung sejumlah senyawa aktif biologis, terutama
anthraquinones. Berbagai in vitro dan in vivo tes telah dilakukan untuk mengevaluasi
cytotoxicity, genotoxicity, dan karsinogenisitas komponen kimia yang terkandung
dalam lateks, terutama Aloe-Emodin, aloin, Emodin, dan dan-thron.
. . . toksisitas lateks
Cytotoxicity Aloe-Emodin telah diselidiki secara intensif. Aloe-Emodin diinduksi
apoptosis melalui berbagai mekanisme, termasuk p53-jalur dependen di T24 sel
kanker kandung kemih manusia [48] dan G2/M siklus sel penangkapan pada manusia
leukemia promielozitov HL-60 sel. [49] selama proses apoptosis yang diinduksi oleh
Aloe-Emodin dan Emodin dalam sel karsinoma skuamosa paru manusia (CH27) dan
sel karsinoma sel nonkecil paru manusia (H460), peningkatan sitokrom sitokrom c,
aktivasi caspase-3, dan perubahan dari protein kinase c (PKC) isozim diamati. [50]
kajian ini juga menunjukkan bahwa stimulasi PKC terjadi di sebuah situs hilir caspase-
3 di jalur apoptosis termediasi Emodin. Studi lain menunjukkan bahwa Aloe emodine
secara signifikan menghambat proliferasi dan diinduksi apoptosis pada keratinocytes
manusia dewasa. [51] gangguan proliferasi Keratinocyte dapat diamati pada
konsentrasi jauh di bawah standar industri untuk produk komersial yang mengandung
ekstrak aloe.
Toksisitas aloin dievaluasi dalam limfosit manusia Jurkat T menggunakan aliran
cytometry dan mikroskop. [52] pengobatan aloin mengakibatkan penurunan ukuran
sel, peningkatan granularity, blok pada fase G2/M dari siklus sel, dan hilangnya kedua
membran integritas dan potensi membran mitokondria dalam cara bergantung pada
dosis, menunjukkan jalur tergantung mitokondria untuk aloin disebabkan apopto-SIS.
UP780, komposisi standar lidah chromone aloesin diformulasikan dengan fillet Aloe
Vera daun batin, menunjukkan tidak ada tingkat efek samping diamati dalam CD-1
tikus dengan pemberian oral UP780 pada dosis 2 g/kg/d untuk 14 hari atau sampai 1
g/kg/d untuk 90 hari. [53]
. . . genotoxicity lateks
Genotoxicity beberapa anthraquinones telah dikonfirmasi dalam berbagai sistem
assay in vitro dan in vivo. Proporsi yang tinggi dari anthraquinones dilaporkan menjadi
mutagenik dalam sejumlah strain Salmonella typhimurium, misalnya, TA1537,
TA1538, TA102, dan TA98. [54 – 56] Strain ini sangat sensitif terhadap mutagens
frameshift. Danthron dan lidah-Emodin positif dalam ketegangan TA1357 baik dengan
dan tanpa aktivasi metabolik. [55] Aloe-Emodin juga disebabkan peningkatan revertant
koloni di strain TA 1537, TA 1538, dan TA 98. [57] Muller dan rekan-rekannya [58]
menyelidiki genotoxicity dari tiga anthraquinones, Emodin, danthron, dan Aloe-Emodin
menggunakan MLA, tes micronucleus, dan alat tes Comet. Pada konsentrasi
mikromolar, ketiga senyawa yang diinduksi tergantung konsentrasi meningkat di
micronuclei dan peningkatan moderat dalam frekuensi mutan dalam sel L5178Y.
Danthron dan lidah-Emodin juga meningkatkan DNA istirahat pada konsentrasi 50 μM
di assay Comet. The genotoxicity dan mutagenicity yang disebabkan oleh
anthraquinones ini adalah karena penghambatan aktivitas katalitik topoisomerase II
(Topo II), dengan danthron menjadi yang paling ampuh. [58, 59] Emodin, senyawa
paling ampuh di antara tiga anthraqinones, menyebabkan jeda untai ganda DNA
dengan menstabilkan kompleks pembelahan Topo II-DNA dan dengan menghambat
hidrolisis ATP Topo II. [60] Aloe-Emodin menyebabkan kerusakan DNA pada sel
karsinoma paru manusia melalui produksi ROS, [61] yang diinduksi micronuclei di TK6
manusia lymphoblastoid sel, [56] dan penyimpangan kromosom dalam hamster Cina
sel ovarium. [57] danthron menyebabkan kerusakan DNA dan kaspase Cascade
dimediasi apoptosis di SNU-1 sel kanker lambung manusia melalui permeabilitas
mitokondria yang transi-tion pori dan jalur Bax-dipicu.
Sebuah tikus in vivo assay Comet dilakukan pada sel ginjal terisolasi dan usus besar
tikus jantan OF1 untuk menunjukkan kemungkinan genotoxicity organospecific Aloe-
Emodin. [56] peningkatan untai DNA istirahat di kedua ginjal dan usus besar diamati
antara 3 h dan 6 h setelah dua administrasi oral di 500, 1000, dan 2000 mg/kg berat
badan, menunjukkan mekanisme genotoksik in vivo tindakan.
Karsinogenisitas lateks
Kegiatan promosi tumor, seperti stimulasi proliferasi sel dan peningkatan transformasi
ganas, telah diselidiki pada tikus selama 9 hidroyan-thraquinones (HA) termasuk
danthron, Aloe-Emodin, dan Emodin. [63] peningkatan 2 sampai 3 kali lipat dalam
sintesis DNA ditemukan di hepatosit utama tikus terkena dan-thron dan Aloe-Emodin;
dan danthron juga meningkatkan transformasi ganas C3H/m2 tikus fibroblas prediobati
dengan N-Methyl-n'-nitro-N-nitrosoguanidine atau 3-methylcholanthrene, menunjukkan
bahwa HA dengan kelompok hidroksi dalam 1, 8-posisi mungkin memiliki aktivitas
meningkatkan tumor. Potensi karsinogenik HA juga telah ditunjukkan dalam kelompok
29 pria ACI/N tikus. [64] setelah 480 hari feed-ing dengan 1% dari ha, 25 dari 29 tikus
dikembangkan adenoma atau adenocarcinoma di sekum atau bagian atas usus besar;
hati Neoplasma (nodul neoplastic dan hep-atokuler karsinoma) diamati pada 12 tikus;
dan tumor perut jinak diamati pada lima hewan. Temuan ini sangat menyarankan
bahwa HA adalah karsinogenik di tikus.
Sebuah studi makan dua tahun Emodin pada pria dan wanita F344/N tikus dan tikus
B6C3F1 menunjukkan bukti tegas dari aktivitas karsinogenik untuk Emodin pada
wanita F344/n tikus karena peningkatan marjinal dalam Kejadian karsinoma kelenjar
zymbal dan pada B6C3F1 tikus jantan yang didasarkan pada insiden rendah
Neoplasma tubulus ginjal. [65] dalam studi tikus, diet yang mengandung 0, 280, 830,
atau 2500 ppm Emodin (setara dengan dosis harian rata-rata sekitar 110, 320, atau
1000 mg/kg untuk pria dan 120, 370, atau 1100 mg/kg untuk perempuan) yang
diberikan untuk 65 laki dan perempuan 65 tikus untuk 105 minggu. Tiga karsinoma
kelenjar Zymbal yang didiagnosis pada tikus perempuan terpapar 2500 ppm. Dalam
studi tikus, 60 tikus jantan dan betina yang diberi makan diet mengandung-ing 0 – 625
ppm (setara dengan dosis harian rata-rata sekitar 15 – 70 mg/kg) atau 0 – 1250 ppm
(setara dengan dosis harian rata-rata sekitar 30 – 120 mg/kg) Emodin, masing-masing,
untuk 105 minggu. Insiden rendah adenoma tubulus ginjal dan satu karsinoma
masing-masing di 312 dan 625 ppm kelompok diamati pada tikus jantan terbuka. Tidak
ada bukti aktivitas karsinogenik Emodin ditemukan pada wanita B6C3F1 tikus bahkan
pada dosis tertinggi 1250 ppm.
Bukti untuk Aloe-Emodin photocarcinogenicity ditemukan pada C3H tikus setelah
pengobatan dikombinasikan dengan radiasi ultraviolet dan Aloe-Emodin dalam etanol
Vehi-Cle. [66] C3H/HeN tikus diperlakukan dengan Aloe-Emodin dalam 25% etanol
secara topikal tiga kali per minggu selama dua minggu dan terpapar 15 kJ/m2 UVB
(280-320 nm) radia-tion. Primer kulit yang mengandung melanin-tumor didiagnosis
dalam 50% – 67% dari UV-irradiated tikus diberikan Aloe-Emodin dalam kendaraan
etanol dan dalam 20% – 30% dari tikus yang diobati dengan kombinasi dari radiasi UV
dan etanol kendaraan, sedangkan tidak ada tumor kulit yang disebabkan oleh Aloe-
Emodin sendirian dengan tidak adanya radiasi UV.
3,3. efek klinis yang merugikan dari lateks pada manusia
Efek purgatif lidah lateks telah lama diakui dan telah digunakan secara empiris untuk
meringankan sembelit. Penulis medis yang paling awal untuk merekam penggunaan
terapi Aloe adalah Dioscorides, seorang dokter Yunani abad pertama A.D. [67] Subse-
quently, lidah lateks digunakan secara luas dalam persiapan pencahar herbal di
banyak coun-mencoba. Dengan demikian, sejumlah efek samping yang dihasilkan dari
menelan lateks telah dilaporkan dalam studi klinis. Penggunaan jangka panjang
dikaitkan dengan ketidakseimbangan elektrolit karena diare, sakit perut, muntah,
hipokalemia, pseudomelanosis Koli, dan pengembangan usus besar katarsis-usus
besar menjadi atonis dan melebar. Penggunaan jangka panjang obat pencahar
anthranoid mungkin berkorelasi dengan risiko terkena kanker usus besar. [68]
Sebuah kasus Aloe-induced Henoch-Schonlein purpura, yang idiopatik vaskulitis dari
pembuluh kecil, dilaporkan. Seorang 52 tahun pasien pria dari Pakistan disajikan
arthralgia parah, purpura teraba, dan sakit perut sepuluh hari setelah mengambil
beberapa jus diekstrak dari empat sampai lima leaflet dari Aloe Vera. Dua puluh empat
jam setelah konsumsi jus, pria mulai memiliki ruam di kakinya dan arthralgia ringan
dari pergelangan kaki. Gejala memburuk pada hari berikutnya, dan ia
mengembangkan menyebar, kolik, sakit perut. Ditandai nekrosis segmental dan
pembentukan bulan sabit ditunjukkan oleh biopsi ginjal. Disfungsi ginjal dan Nefritis
dianggap sebagai konsekuensi dari dosis besar Aloe. [69]
Seorang perempuan berusia 74 tahun disajikan dengan pigmentasi hitam yang
mendalam mengesankan dari seluruh usus besar setelah penggunaan kronis obat
pencahar anthraquinone selama beberapa dekade. Berbagai adenoma, yang
diklasifikasikan sebagai lesi prakanker, terdeteksi, tetapi tidak ada karsinoma
kolorektal ditemukan. [70] sebuah 18-tahun gadis Kaukasia, yang diperlakukan
dengan kombinasi pencahar yang mengandung 5 ml danthron oral di malam hari
untuk memperbaiki sembelit dari 14 bulan berusia 5 – 6 tahun, disajikan
Leiomiosarkoma usus kecil dengan penyebaran tersebar luas. [71] meskipun satu
kasus tidak dapat membuktikan hubungan kausatif antara danthron dan risiko terkena
kanker usus, para penulis menyimpulkan bahwa paparan lisan berkepanjangan
terhadap pencahar harus dihindari pada anak usia dini. Selain itu, wanita hamil
disarankan untuk tidak mengambil lateks lidah karena properti yang katarsis mungkin
mengakibatkan merangsang kontraksi rahim, sehingga meningkatkan risiko persalinan
prematur atau keguguran. Juga, ibu menyusui tidak harus mengambil obat pencahar
karena kemungkinan anthraquinones menyebabkan diare pada bayi. 3
4. Aloe Vera gel
4,1. komponen
Gel lidah buaya adalah zat jeli mucilaginous transparan-seperti yang terkandung
dalam sel parenkim dari pulp daun Aloe Vera segar, dengan hasil gel sekitar 70% (70
g gel/100 g pulp) dari pulp oleh ekstrusi mekanis. [72] gel memiliki kadar air yang
sangat tinggi (99% – 99.5%), dengan kandungan padatan larut yang tersisa
naik 0,5% – 1%, [73] dan kisaran tingkat keasaman gel (pH) 4,4 – 4,7. [74] pada dasar
yang kering, konstituen kimia terdiri dari 35% serat makanan (nonpati polisakarida
lignin), 27% gula larut, 24% abu, dan sebagian kecil lipid, protein, enzim, dan elemen
mineral. [7, 72] residu yang tidak larut dalam alkohol yang Diperoleh dari pecahan gel
lyophilized Aloe Vera memiliki kandungan karbohidrat yang tinggi (72%) termasuk
mannose, glukosa, dan asam uronik. Rantai linear dari molekul manusia β-1-4-Linked-
hidung dan glukosa membentuk polisakarida primer pada rasio 1 ∼ 22:1 dalam gel. [6,
7, 75 – 77] Kebanyakan penyelidik sepakat bahwa acemannan, sebuah glukomannan
acetylated, membentuk komponen aktif utama dari Aloe Vera gel mucilaginous, [72]
sementara yang lain melaporkan zat pektis sebagai polisakarida utama. [73]
perbedaan tersebut dianggap sebagai hasil dari perbedaan dalam spesies, musim
tahun, lokasi geografis, dan proses ekstraksi gel.
4,2. toksisitas, genotoxicity, dan karsinogenisitas
Efek toksik dari Aloe Vera gel telah dilaporkan hanya dalam beberapa studi. Ada
keragaman dalam hasil efek beracun yang diamati yang mungkin sebagian besar
karena perbedaan dalam isi gel yang sangat dipengaruhi oleh berbagai faktor
termasuk musim, lokasi, irigasi, waktu panen, dan, yang paling penting, kurangnya
standardisasi persiapan gel.
. . . toksisitas gel
Sitotoksisitas Aloe Vera gel telah dikonfirmasi dalam monolayers ayam fibroblas
berdasarkan pengamatan dari persimpangan interselular yang terganggu dan
pembentukan kesenjangan bebas sel dalam monolayers setelah pengobatan. [78] alat
uji cedera sel dilakukan dengan menggunakan tiga pecahan yang terisolasi dari daun
Aloe barbadensis, gel asli (mucilaginous parenchymous Tissue tergores dari daun
Aloe), gel murni (fraksi nondialyzable dari gel asli), dan fraksi bobot molekul rendah
(LMWF, bahan dialyzable). Pengenceran 1:10 gel asli dan LMWF dipromosikan
cedera sel yang sama, sementara gel murni berperilaku seperti kontrol pada
pengenceran yang sama. Kerusakan selular yang parah ini cukup berbeda untuk
dideteksi di bawah mikroskop. Oleh karena itu, diusulkan bahwa toksisitas terutama
disebabkan oleh LMWF dari gel karena karakteristik menguntungkan disarankan untuk
hasil dari komponen berat molekul tinggi. [78] setelah pengobatan 4 jam, bahan gel
Aloe Vera dehidrasi diinduksi tergantung sitotoksisitas dalam sel HeLa, dengan nilai
CC50 269,3 mg/ml. [21]
Aloe Vera gel diberikan dalam air minum untuk kelompok empat pria dan empat
Perempuan F344/N tikus dalam studi 14-hari yang dilakukan oleh NTP. [28] kualitas
gel dipantau oleh kandungan asam malic dan aloin A (barbaloin). Larutan air minum
0,5% – 3% Aloe Vera gel mengandung 1060 – 6360 μg asam Malat/g air, dan 5.6 –
33.3 μg aloin A/g air. Setelah paparan 14 hari, dosis yang terkait meningkat dalam
kadar glukosa urin perempuan tikus dan dosis terkait penurunan tren kadar serum
trigliserida, kolesterol, dan albumin diamati pada konsentrasi 1,5%
atau lebih besar pada tikus betina dan 3,0% pada tikus jantan. Ketika pria dewasa
Wistar tikus yang diberikan secara lisan dengan Aloe Vera gel ekstrak solusi (150 dan
300 mg/kg/hari) untuk 8 minggu, berat testis, testosteron serum, jumlah sperma, dan
sperma Fer-aktilitas secara signifikan menurun dibandingkan dengan kontrol tikus. [79]
dalam studi lain di Vivo menggunakan stabil komersial Aloe Vera gel dikonsumsi
sebagai minuman, tidak ada perubahan yang ditemukan dalam konsumsi pakan, berat
badan gain, dan tes kimia serum berikut 13-minggu paparan subkronis B6C3F1 tikus.
[80]
Setelah 5,5 bulan menelan mentah berkulit Aloe filet untuk pria F344 tikus, tidak ada
efek samping diamati pada berat badan, asupan makanan, waktu transit
gastrointestinal, atau patologi bruto pada konsentrasi Diet 1% atau 10% (sesuai
dengan dosis Aloe Vera gel ∼ 0,33 dan 3,3 g/kg BW/Day). [16, 81] hidup lama
konsumsi dosis rendah (1%) Filet lidah buaya tidak menyebabkan efek berbahaya
yang jelas atau perubahan yang merugikan pada tikus. [82]
. . . genotoxicity gel
Studi tentang efek biologis dari ekstrak pulp Aloe Vera pada Escherichia Koli-
kekurangan perbaikan mutan dan plasmid DNA mengungkapkan sifat genotoksik gel,
tetapi tidak cytotoxicity karena permeabilitas miskin melalui membran sel. The
Agarose gel Elektroforesis assay menunjukkan bahwa Aloe Vera pulp Extract
dihasilkan dosis tergantung tunggal-untai istirahat dalam DNA plasmid. [83] studi
keamanan in vitro dan in vivo menggunakan persiapan fillet daun batin Aloe Vera yang
sangat murni menunjukkan bahwa gel tersebut nonmutagenic dalam tes Ames, tes
aberasi kromosom, dan tes micronucleus sumsum tulang di vivo, berikut pemberian
oral pada dosis hingga 5 g/kg BW/hari untuk tikus untuk 90 hari [84] demikian pula, jus
gel komersial tidak menginduksi peningkatan yang signifikan dalam perbaikan SOS
DNA dalam Escherichia koli atau insersional di Salmonella TA100 [80]
. . . karsinogenisitas gel
Tidak ada data karsinogenicity yang tersedia untuk gel lidah buaya.
4,3. efek klinis yang merugikan dari gel pada manusia
Gel lidah buaya pertama kali digunakan secara klinis pada tahun 1930-an untuk
pengobatan luka bakar radiasi. [34] setelah itu, beberapa uji klinis Aloe Vera gel telah
dilakukan dalam pengobatan luka bakar, [85] lichen planus oral, [86] pasien
hiperlipidemia tipe 2 dia-betic, [87] dan stomatitis aphthous berulang. [88] hanya
beberapa efek samping kecil dilaporkan dalam studi ini, seperti ketidaknyamanan,
rasa sakit, dan perkembangan reaksi hipersensitif. Namun, eczematous Umum dan
dermatitis papular ditemukan pada pasien pria dalam menanggapi penggunaan oral
dan topikal Aloe Vera gel. [89] eritema pruriginous diamati pada kaki dan kelopak mata
wanita berusia 72 tahun setelah menerapkan jus daun Aloe Vera buatan sendiri di
atas kaki. [90] pemulihan yang sangat lambat dari dermatitis yang disebabkan oleh
persiapan Aloe Vera dilaporkan dalam empat kasus setelah dermabrasi dan
pengelupasan kimia. [91] tidak ada efek samping yang parah atau genicity carcino
telah dilaporkan dari menggunakan Aloe Vera gel.
5. perspektif
Lebih dari 300.000.000 orang di seluruh dunia mengkonsumsi suplemen diet dan
tanaman herbal, dan sekitar satu-setengah dari Amerika menggunakannya secara
teratur. [92] produk suplemen diet atau herbal diharapkan aman, efektif, dan
berkualitas sesuai. Namun, sifat kimia kompleks suplemen diet membuat sulit untuk
mengevaluasi efektivitas dan keamanan. Produk herbal sering menunjukkan
variabilitas yang besar dalam kualitas karena beberapa masalah termasuk otentikasi,
pemalsuan dan substitusi, dan faktor selama pertumbuhan, panen, dan pengolahan
Pascapanen. [93] otentikasi spesies tanaman yang digunakan untuk persiapan
suplemen diet herbal penting untuk jaminan keselamatan. Selain pendekatan
tradisional, penggunaan molekul/profil genetik dalam identifikasi perubahan molekuler
tertentu (sidik jari) dan dalam mengungkapkan tanda tangan yang menunjukkan
eksposur tetap menjanjikan namun masih sebagian besar pendekatan belum
dijelajahi. [94, 95]
Efek samping yang dilaporkan telah mengangkat keprihatinan risiko kesehatan
masyarakat mengenai konsentrasi, komposisi, dan kontaminan individu suplemen diet.
Suplemen diet herbal dan produk herbal lainnya telah diakui sebagai penyebab umum
cedera hati akibat obat. [96] laporan baru-baru ini menunjukkan bahwa suplemen
diet/herbal terlibat dalam 19% obat-induced kasus gagal hati akut, [97] karena
konsumen sering membeli produk ini secara online tanpa pengawasan dari penyedia
layanan kesehatan dan tidak menyadari obat-ramuan interaksi dan peringatan yang
sesuai. Total 1179 bahasa Inggris, produk herbal situs terkait (termasuk eceran dan
nonretail website) yang diperiksa dan hanya
∼ 10% dari mereka dianjurkan konsultasi dengan perawatan kesehatan profesional.
Selain itu, hanya sekitar 8% pengecer internet yang memberikan informasi tentang
potensi efek samping, interaksi obat, dan tindakan pencegahan dasar lainnya; dan
kurang dari 3% dikutip referensi ilmiah untuk klaim mereka. [98]
Tanaman lidah mengandung beberapa konstituen dengan potensi bermanfaat dan
aktivitas Toksikologi. Tiga persiapan yang berbeda yang berasal dari Aloe Vera (yaitu,
ekstrak daun seluruh, Aloe Vera gel, dan Aloe Vera Latex) telah digunakan sebagai
obat topikal dan oral terapi. Gel ini terutama digunakan secara topikal untuk luka dan
masalah kulit, serta diambil secara lisan untuk pengobatan ulkus gastrointestinal dan
dia-betes. [9] lateks diatur sebagai obat oleh FDA untuk meringankan sembelit dan
ekstrak seluruh daun mungkin memiliki aktivitas antibakteri/virus dan antikanker. [5]
Aloe Vera tampaknya aman ketika digunakan sebagai penyedap makanan [16]; dan
bahan polisakarida yang berasal dari gel bagian dalam adalah nonsitotoksik
sebagaimana dievaluasi oleh panel ahli tinjauan bahan kosmetik. [3] Namun, karena
cytotoxicity, mutagenicity, dan karsinogenisitas anthraquinones, sangat penting untuk
memantau isi dari senyawa fenolik ini dalam ekstrak daun seluruh lidah buaya dan
lateks. [5, 24] International Aloe Science Council standar menunjukkan bahwa konten
yang diizinkan maksimum aloin Aloe bahan turunan untuk konsumsi oral kurang dari
10 ppm (bagian per mil-singa); untuk penggunaan nonmedical batas yang disarankan
adalah 50 ppm atau lebih rendah. [3, 99]
Menurut analisis data terpadu multinasional yang dilakukan oleh kesehatan IMS
(Danbury, CT), perkiraan penjualan global produk Aloe telah mencapai US
$351.000.000. [16] karena meningkatnya popularitas dan pemanfaatan tanaman lidah,

dalam studi mendalam diperlukan untuk menyelidiki efek samping, interaksi obat
konvensional, dan kemungkinan efek toksik dan karsinogenik dari persiapan Aloe,
terutama setelah penggunaan jangka panjang dari produk ini.
Pengakuan
Kami berterima kasih kepada Drs. Robert H. Heflich, Page B. McKinzie, dan Vasily N.
Dobrovolsky untuk membantu mereka saran dan komentar. Informasi dalam materi ini
bukan merupakan penyebaran informasi formal oleh administrasi makanan dan obat
AS dan tidak mewakili posisi atau kebijakan agensi.

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Aloe Vera – A Review of Toxicity and Adverse Clinical Effects

Article in Journal of Environmental Science and Health Part C · March 2016

Xiaoqing Guo Nan Mei

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ISSN: 1059-0501 (Print) 1532-4095 (Online) Journal homepage: http://www.tandfonline.com/loi/lesc20

Aloe vera: A review of toxicity and adverse clinical

Xiaoqing Guo & Nan Mei

Accepted author version posted online: 17

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Download by: [FDA Library] Date: 11 May 2016, At: 04:11

Aloe vera: A review of toxicity and adverse clinical eﬀects

ciated with diarrhea, hypokalemia, pseudomelanosis coli, kid-

Aloe All  

as a high-priority candidate for a carcinogenicity study under the National Toxicol-

2. Aloe vera whole leaf extract

2.2 Toxicity, genotoxicity, and carcinogenicity

and administered intraperitoneally to adult albino mice at an initial dose of 400 to

which is one-fifth of the pharmacologically active dose, for a period of 3 months.[23]

... Genotoxicity of the whole leaf extract

extract showing a positive response at lower concentrations than the decolorized

... Carcinogenicity of the whole leaf extract

2.3. Adverse clinical effects of the whole leaf extract in humans

3. Aloe vera latex or exudate

3.2. Toxicity, genotoxicity, and carcinogenicity

... Toxicity of the latex

promyelocytic leukemia HL-60 cells.[49] During the apoptosis process induced

sis. UP780, a standardized composition of aloe chromone aloesin formulated with

... Genotoxicity of the latex

... Carcinogenicity of the latex

3.3. Adverse clinical effects of the latex in humans

4. Aloe vera gel

up 0.5%–1%,[73] and a range of gel acidity (pH) of 4.4–4.7.[74] On a dry matter

4.2. Toxicity, genotoxicity, and carcinogenicity

... Toxicity of the gel

... Genotoxicity of the gel

... Carcinogenicity of the gel

4.3. Adverse clinical effects of the gel in humans

[31] Yokohira M, Matsuda Y, Suzuki S, Hosokawa K, Yamakawa K, Hashimoto N, Saoo K, Nabae

[51] Popadic D, Savic E, Ramic Z, Djordjevic V, Trajkovic V, Medenica L, Popadic S. Aloe-

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Aloe Vera – review toksisitas dan efek klinis yang merugikan

2. Aloe Vera ekstrak seluruh daun

. . . karsinogenicity dari ekstrak daun seluruh

. . . karsinogenicity dari ekstrak daun seluruh

. . . karsinogenicity dari ekstrak daun seluruh

. . . karsinogenicity dari ekstrak daun seluruh

3,2. toksisitas, genotoxicity, dan karsinogenisitas

4. Aloe Vera gel

$351.000.000. [16] karena meningkatnya popularitas dan pemanfaatan tanaman lidah,

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