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Review - Aloe Vera
Review - Aloe Vera
Abstract.
Aloe vera is a plant that has been historically used in many cultures all around the world
for the treatment of a wide variety of health problems; moreover, in present day, this plant
is used in a lot of products of common that range from foods to cosmetics. However, for a
long time, it wasn’t known the scientific basis for the medicinal properties attributed to
Aloe vera. In recent years, efforts have been made in order to establish the identity of the
compounds of Aloe vera that are responsible for all of its medicinal properties. In this work,
information of several of these research articles is compiled with the purpose of illustrating
the most important biologically active compounds that are found in Aloe vera, with their
respective biological activities; proving the effectiveness of this plant as a powerful
medicinal agent.
Contents
Page
1. Introduction 2
2. Botanical information 2
2.1. Taxonomy 2
2.2. Plant description 3
3. Isolated metabolites and activity 3
3.1. Carbohydrates 3
3.2. Phenolic compunds 6
3.3. Phytosterols 8
3.4. Enzymes 9
3.2. Minerals 9
4. Traditional and medicinal Applications 10
6. Conclusions 11
7. Bibliography 11
1. Introduction.
A variety of medicinal plants exist in the world; amongst them, are Aloe plants, which have
had a long history of providing an array of health benefits and are one of the most used
herbal remedies around the world. Over 400 Aloe species exist, but the most known and
most used one is Aloe vera (A. vera) (Guo & Mei, 2016) and it likely is the most used
medicinal plant in present day (Sánchez-machado, López-cervantes, Sendón, & Sanches-,
2017).
In ancient Egypt, A. vera was known as the “plant of immortality”, and it has been used as
a traditional medicine in many cultures, including Arabic, Chinese, Egyptian, Greek,
Indian, Japanese, Korean and Roman, for over two thousand years, mainly for the treatment
of skin problems such as wounds, burns or psoriasis, as well as to treat constipation, ulcers
and lupus erythematosus disease (Guo & Mei, 2016). This plant is native to south and east
Africa, around the superior Nile river around Sudan; it was subsequently introduced to
north Africa y into the Mediterranean region (Sahu, Giri, Singh, Pandey, & Gupta, 2013).
It is currently found all around the world, but it grows mostly in tropical areas (Maan et al.,
2018).
These uses given to A. vera have been verified in recent times by science, having found
over 200 bioactive compounds in different parts of the plant, including amino acids, sugars,
enzymes, vitamins, minerals, saponins, anthraquinones, lignin and salicylic acid (Maan et
al., 2018). Acoording to the World Health Organization (WHO), medicinal plants are the
best source for the obtention of a wide variety of medicines (Sahu et al., 2013), which is
why it results very interesting to understand which are the compounds responsible for the
biological activity of A. vera and apply them in medicine. The purpose of these review is
to summarize which are the most important bioactive compounds in the plant of A. vera,
as well as their corresponding biological ativity.
2. Botanical information
2.1 Taxonomy
Aloe vera (L.) Burm. F is the scientific of the plant, but another accepted and used scientific
name is Aloe barbadensis Mill. It belongs to the Aloeceae family (table 1), which is related
to the lily family, including garlic and onion, plants that are well known for their chemical
properties.
3.1 Carbohydrates:
Acemannan (figure 1) is a storage polysaccharide located inside the protoplast of the
parenchyma cells of A. vera gel. It is mainly composed of a main chain of β1-4 partially
acetylated mannose (>60%) and glucose (approximately 20%) with galactose side chains,
bound to mannose units by β1-6 bonds. Acetylation occurs in a 1:1 rate o higher, at C2, C3
or C6 positions (Minjares-Fuentes & Femenia, 2019).
Kumar & Tiku extracted acemannan from A. vera by separating the gel from the rind and
the latex; it was then washed with tap and centrifuged at 10000g, the supernatant was
centrifuged again at 38000g, and acemannan was obtained by precipitation with three times
its volume in ethanol and centrifugation, obtaining a yield of 171±25mg. Acemannan was
quantified in this extract using the anthrone method, finding that it accounted for 51,4%,
which is This compound was studied for its immumonodulatory activity, finding that it
induced proliferation of mother hematopoietic cells, which produces an increase in the
amount of lymphocytes (a type of blood cell). Treatment with acemannan increases
Biolocally Active Compounds of Aloe vera: A review
4
lymphocyte count after radiation exposure; this indicates that acemanan protects against
hematopoietic lesions induced by radiation, or that it can induce hematopoiesis. It was also
found that acemannan increases levels of the cytokines interleukin-1 (IL-1) and tumor
necrosis factor-alpha (TNF-α), which results in radiation resistance. This protective effect
is also due to the decrease in the inflammatory cytokine interleukin-6 (IL-6). There was a
decrease in NO levels, indicating that acemannan induced cytokines are not causing
inflammation. Finally, treatment with acemannan on radiation exposed mice significatively
increased survival, both in its pre-radiation and post-radiation exposure application. These
results are specially important for people with cancer who have been trated with
radiotherapy , because this kind of radiation causes a decrease in lymphocytes (Kumar &
Tiku, 2016).
Acemannan Glucomannan
Figure 1. Structure of biologically active carbohydrates from Aloe vera
Acemannan also has an important activity in the induction of wounded tissue repair, which
might be because of its acetylated mannose units (Minjares-Fuentes & Femenia, 2019).
Chokboribal et al. extracted acemannan from A. vera following the same method employed
by Kumar & Tiku, but it was characterized using 1H Nuclear Magnetic Resonance (1H
NMR), Size-exclusion High Performance Liquid Chromatography (HPLC) and Fourier
Transform Infrared Spectroscopy (FTIR). These authors found that the tissue repair activity
of A. vera is owed to an increase in the expression of vascular endotelial growth factor or
VEGF, a protein that acts an angiogenic factor, meaning, it stimulates the formation of
blood vessels from already existing vasculature. Aditionally, acemannan increases the
expression of type I collagen, the most abundant protein in the body, it is found in the skins,
tendons, cornea, blood vessel walls, being very important in the scarring process. This
compound aids in the incorporation thymidine to new cells and the proliferation of human
gingival fibroblasts, which are responsible of the synthesis of extracellular matrix
compounds such as connective tissue, more specifically, elastin (Chokboribal et al., 2015).
Stuart et al. investigated the antifungical activity of commercially obtained acemannan
(Carrington laboratories); exposition of phagocytes to acemannan causes an increase in the
level of phagocytosis against the fungus Candida albicans (candidacidal activity). An
increase of phagocytosis was found, which was dependent on time and the dose of
acemannan, in a way that, an incubation time of one hour results in the death of 98% of the
fungus. This effect isn’t specific for this type of fungus, given that experiments against
Escherichia coli also showed similar results (Stuart et al., 1997).
Acemannan content in A. vera has been determined in different studies, which results are
shown in table 2, along with the method used for this purpose.
(isobarbaloin), which have similar chemical properties. It is found exclusively in the latex
of the leaves; it is the compound that a bitter taste to most of Aloe vera based drug. Aloin
A is the pharmacological compound extracted form Aloe species. Another compound that
belongs to the group of anthraquinones is aloe-emodin. The structure of anthraquinones is
observed in figure 2. The other important group of phenolic compounds in Aloe vera
corresponds to chromones, which are derivatives of benzopyran with a substituted keto
group in the pyran ring, this group includes isoaloeresin and aloesin.
Aloe-emodin
Aloin
Isoaloeresin Aloesin
Figure 2. Biologically active phenolic compounds from A. vera.
Lee et al. identified several metabolites from A. vera leaves; samples were extracted with
methanol and subjected to centrifugation. This extract was then dried completely and
derivatized for gas chromatography−ion trap−mass spectrometry (GC-IT-MS) analysis and
re-dissolved in methanol for ultra performance liquid chromatography−quadrupole−time
of flight−mass spectrometry (UPLC-Q-TOF-MS) analysis. Several compounds were
identified in the extract; but only three of them were studied for their antioxidant activity.
Both aloin A and aloin B, as well as aloeresin have antioxidant activity against ABTS and
DPPH radicals. Which can be caused by its phenolic group; among these compounds, aloin
presented the highest antioxidant activity (S. Lee et al., 2012).
El-Shemy et al. performed a Supercritical Fluid Extractiom (SFE) on A. vera rind and latex
using carbon dioxide and further purified using HPLC. Extracted aloin, aloe-emodin and
isoaloeresin were found to prevent the formation of tumors by means of the modulation of
the activity levels of antioxidant and detoxification enzymes. This was tested in vitro with
three lines of cancer cells: acute myeloid leukemia (AML), acute lymphoblastic leukemia
(ALL) and Ehrkich ascites carcinoma (EACC). Finding a level of cytotoxicity dependent
Biolocally Active Compounds of Aloe vera: A review
7
(Gulia,
Sharma,
Methanol/water
Sarkar,
Aloin 0,0106 mg/g dissolution, C18 HPLC
Upadhyay,
SPE
& Shitandi,
2010)
Aloin 1,499 mg/g Ethanol
(Y. S. Lee
Aloe- extraction, HPLC
0,00552 mg/g et al., 2011)
emodin centrifugation
3.3 Phytosterols
Phytosterols are compounds found in plants that are analogous to cholesterol in animals.
Some bioactive phytosterols have been found in Aloe vera, their structure is shown in figure
3.
Cycloartanol
24.methylene cycloartanol
Lophenol
24-methyl-lophenol 24-ethyl-lophenol
Tanaka et al. extracted and elucidated the structure of five A. vera phytosterols; for this
purpose, dried A. vera gel was extracted with chloroform/methanol mixture, this extract
was then successively fractionated using column chromatography until pure components
were found in the following contents in A. vera gel: cycloartanol 10,9 mg/kg, 24-
methylene-cycloartanol 9,4 mg/kg, lophenol 4,2 mg/kg, 24-methyl-lophenol 5,9 mg/kg and
24-ethyñ-lophenol 0,2 mg/kg. All of these phytosterols were proven effective in fighting
diabetes, this is, they have hypoglycemic activity, they reduce glycosylated hemoglobin
levels and they increase sensibility to insulin, these results were evaluated in vivo, using
Biolocally Active Compounds of Aloe vera: A review
9
type 2 diabetic mice. Unlike other phytosterols, such as β-sitosterol, these compounds did
not diminish blood cholesterol levels (Tanaka et al., 2006).
More recently, Misawa et al. isolated cycloartanol and lophenol using the same method as
Tanaka et al., and tested their capacity to ameliorate obesity related symptoms. It was found
that these compounds induce the expression of glycolytic enzymes and reduce the
expression of gluconeogenic enzymes. Both of these phytosterols are also capable of
reducing weight gain, specifically, they reduce gain in visceral fat in diabetic mice; which
is probably due to increased expression of lipolytic enzymes as well as suppression of
lipogenic enzymes. Finally, these sterols also exhibited the capacity to reduce serum and
hepatic triglyceride and non-sterified fatty acid levels; while also reducing hepatic total
cholesterol content, without significant changes in serum total cholesterol levels (Misawa
et al., 2012).
3.4 Enzymes
Ahmed and Hussain determined enzyme activity of whole and dried A. vera leaves. SOD
activity was measured by colorimetry as the photoreduction of nitroblue tetra zolium;
catalase activity was determined by change in absorbance of a H2O2 and enzyme extract;
similarly, peroxidase activity was determined at 470nm in a solution with H2O2 and
guaicol. The extract presented moderate, concentration dependent, activity of antioxidant
enzymes catalase and peroxidase, which perform the important function in biological
systems of scavenging reactive peroxide species. More importantly, the superoxide
dismutase active of Aloe vera leaves is very high; this enzyme functions in the
transformation of superoxide (O2-) radical into two less damaging species, hydrogen
peroxide and oxygen (Ahmed & Hussain, 2013). Results of this study are shown in table
4.
Table 4. Enzymatic activity of Aloe vera leaves
Extract concentration (mL extract/mL distilled water)
Constituents
1/10 1/20 1/30
Superoxide dismutase 2830.19 ± 37.09 1244.81 ± 70.4 802.14 ± 55.6
Catalase 2.8 ± 0.19 1.81 ± 0.02 1.56 ± 0.14
Peroxidase 3.72 ± 0.19 2.32 ± 0.11 1.46 ± 0.06
3.5 Minerals
Rajasekaran et al. obtained ashes from A vera gel by heating between 410°C and 440°C
overnight, and element composition (shown in table 3) was determined by digestion in
hydrochloric acid and atomic absorption spectroscopy. These ashes were tested for their
antidiabetic activity in type 1 diabetic rats. Results showed a recovery of weight loss due
to muscle protein breakdown, along with reduced blood urea and increased plasma
proteins; reduction in blood glucose, as well as glycosylated hemoglobin; and
normalization on the activity of hexokinase, glucose-6-phosphatase and fructose-1,6-
diphosphatase. Overall these results indicate normalization of protein and glucose
metabolism which becomes deranged in diabetic condition. The reason of these effects is
not entirely known, but it may be related to the involvement of some of these inorganic
elements in metabolism; such as the role of potassium and calcium in insulin release, the
insulinomimetic effect of zinc or the insulin binding properties of copper (Rajasekaran,
Sivagnanam, & Subramanian, 2005).
5. Conclusions.
Several studies regarding A. vera have taken place in the last decades; in an effort to
identify biologically active compounds present in it and understand how it exerts so many
medicinal properties. Several types of compounds have been identified; among which are
polysaccharides such as acemannan, glucomannan and aloeride; phenolic compounds such
as aloin, aloe-emodin, isoaloeresin and aloesin; phytosterols such as cycloartenol, 24-
methylene-cycloartanol, lophenol, 24-methyl-lophenol and 24-ethyl-lophenol; enzymes,
which are superoxide dismutase, catalase and peroxidase and finally, A. vera ashes,
composed of several metal ions. Isolation of these compounds and studies on their
biological activities have found that they are useful as antioxidants, antimicrobials, anti-
inflammatories, anti-cancer, anti-diabetic, anti-obesity, immunomodulators, amongst
others. All of these results indicate that A. vera is indeed a powerful plant with a variety of
medicinal uses as well as a potential source for different kinds of pharmaceutical
compounds.
6. Bibliografia
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Jettanacheawchankit, S., & Thunyakitpisal, P. (2015). Deacetylation affects the
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