Biomedicine & Pharmacotherapy 84 (2016) 759772

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Review

Therapeutic effects of Aloe spp. in traditional and modern medicine: A

review
Maryam Akaberia , Zahra Sobhanib , Behjat Javadib , Amirhossein Sahebkarc,d ,
Seyed Ahmad Emamia,b,*
a
Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
b
Department of Traditional Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
c
Neurogenic Inammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
d
Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

A R T I C L E I N F O A B S T R A C T

Article history:
Received 29 June 2016 Traditional medicine is a useful guide in medical sciences. In the Islamic Iranian traditional medicine, the
Received in revised form 24 September 2016 medicinal properties of many plants have been mentioned that could be exploited in drug discovery. We
Accepted 24 September 2016 aimed to explore the nature and properties of Aloe spp. As described in some major Islamic traditional
texts including Ferdows al-Hekmah l-Tibbe (The Paradise of Wisdom in Medicine), Al-Hawi l-Tibb
Keywords: (Comprehensive Book of Medicine), Kamel al-Sanaat al-Tibbyyah (Complete Book of the Medical Art), Al-
Islamic traditional medicine Qanun l-Tibb (Canon of Medicine), Zakhireh Kharazmshahi (Treasure of Kharazmshah), and Makhzan
Aloe al-Adwiah (Drug Treasure), and assess the conformity of traditional medicine instructions with the
Drug discovery
ndings of modern pharmacological studies. Gastrointestinal activities, hepato-protective properties,
Xanthorrhoeaceae
benecial effects against skin problems such as wounds, injuries, and infective diseases are among the
most frequently mentioned properties of Aloe spp. Several activities of Aloe spp. described in traditional
medicine have been the subject of recent in vitro and in vivo studies as well as clinical trials. Owing to the
positive ndings, different preparations of Aloe spp. are now present in pharmaceutical markets such as
Aloe cosmetic products. On the other hand, there are many traditional therapeutic effects of Aloe spp.
which have not been studied and require conrmatory experimental or clinical investigations. It is hoped
that the present study could stimulate further research on the unexplored aspects of the medicinal
properties of Aloe spp.
2016 Elsevier Masson SAS. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 760
2. Nature of Aloe spp. described in ITM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
3. Botany of Aloe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
4. Phytochemicals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
5. Medicinal uses of Aloe spp. in ITM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
5.1. Liver and kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
5.2. Gastrointestinal system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
5.3. Upper respiratory tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 765
5.4. Reproductive (genital) organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 766
5.5. Central and peripheral nervous systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 766
5.6. Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 766
5.7. Eyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769

* Corresponding author at: Department of Traditional Pharmacy, School of

Pharmacy, Mashhad University of Medical Sciences, Mashhad 917751365, Iran.
E-mail addresses: sahebkara@mums.ac.ir (A. Sahebkar), emamia@mums.ac.ir
(S.A. Emami).

http://dx.doi.org/10.1016/j.biopha.2016.09.096
0753-3322/ 2016 Elsevier Masson SAS. All rights reserved.
760 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772

5.8. Joints and muscles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769

5.9. Hair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769
6. Toxicity and safety studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769
7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769
Conict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770

1. Introduction

Plants belonging to the genus Aloe have a long history of popular

and traditional use in the Islamic traditional medicine (ITM). It has
been used as a folk remedy for the treatment of a wide range of
illnesses, including skin problems and gastrointestinal disorders.
Hitherto, only few species of Aloe have been considered for
commercial and pharmaceutical uses, of which Aloe vera is
considered as the most widely studied and commercialized
species [13]. Aloe spp. has not only been used in traditional
medicine, but exhibited various pharmacological properties
according to the ndings of modern pharmacological studies.
Numerous in vitro and in vivo pharmacological studies as well as
clinical trials have conrmed the traditional uses of Aloe including
wound healing and anti-ulcer activities. These studies have also
indicated new properties such as anti-diabetic, hypoglycaemic,
anti-cancer, antimicrobial, antiviral, antihyperlipidemic and anti-
ulcer activities [4].
The use of plants as medicines or food stuff dates back several
millennia. Nowadays, various strategies are being used to nd new
and effective drugs from natural sources. To this end, investigating
folk and traditional medicine systems, such as Islamic traditional
medicine (ITM), is a rational strategy owing to their antiquity and
long-term history of human use. In ITM, a considerable attention
has been paid to the qualities of individual herbs. The general and
specic properties of each herb such as its nature, natural habitat,
energy pattern, effects, indications, duration of action, relation-
ships to the body organs, toxicity and contraindications, dosage,
types of preparations, and antidotes are discussed in ITM [5]. In the
Islamic school, expert scientists like al-Majusi (Haly Abbas), ar-
Rhazi (Rhazes) and Ibn-Sina (Avicenna) could establish notable
developments. In the present study, we aimed to summarize the
information about Aloe spp. described in major ITM texts. As a
secondary aim, we tried to assess the conformity of ITM
instructions with the ndings obtained from modern pharmaco-
logical studies. The names of books that were explored for this
Fig. 1. An illustration of A. vera as the most studied species in the genus Aloe.
review are listed in Table 1.

Table 1
Information regarding major ITM books that described medicinal effects of Aloe.

Author Living period Book Language

Ahwazi Arjni, AA. 930994 C.E Kamel al-Sinaah al-Tibbiyah Arabic
Akhawayni Bukhari, RA. 10th century Hidayat-al-Mutaallimin al-Tibbe Persian
Antaki, DO. 15351599 C.E. Tadhkirat Oli al-Albb wa al-Jme le al-Ajb al-Ujb Arabic
Ansri, AH. ?1403 C.E. Ekhtiyrt Badii Persian
Aqili Khorasani, MH. 18th century Makhzan al-Adwiah Persian
Biruni, MA. 9731048 C.E. Al-Saydanah Arabic
Ghasani, AM. 15471611 C.E. Hadiqat al-Azhr Mhiyyat al-ushb wa al-uqqr Arabic
Herawi, AR. 10th century Al-Abniyah an Haqyeq al-Adwiah Persian
Husseini Tonekaboni, MM. 17th century Tohfah al- Momenin Persian
Ibn Al-Baytr, AA. 11931248 C.E. Al-Jmee le Mofrad t al-Adwiah wa al-Aghziah Arabic
Ibn Nas Qarshi 1210-1288 C.E. Al
Shamel al-Tibbe Arabic
Ibn Sina, HA. 9801037 C.E. Al-Qnun al-Tibbe Arabic
Jorjni, SI. 10421136 C.E. Zakhireh Khrazmshhi Persian
Jorjni, SI. 10421136 C.E. Al-Aghrz al-Tibbiah wa al-Mabhethi al-Aliiah Persian
Razi, MZ. 865925 C.E. Al-Hwi al-Tibbe Arabic
Tabari, MA. 773861 C.E. Ferdows al-Hekmah l-Tibbe Arabic
Torkamni YO. 12221294 C.E. al-Motamad al-Adwiyah al-Mofradah Arabic
 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772 761

Table 2
The main phytochemicals of Aloe spp.

Phytochemical Class Components Ref.

Anthraquinones Aloe-emodin, aloesaponarin, chrysophanol, desoxyerythrolaccin, 1,5-dihydroxy-3-hydroxy methylanthraquinone, [3234]
helminthosporin, 7-hydroxyaloe emodin, isoxanthorin) laccaic acid D methyl ester, nataloe emodin and its ester nataloe
emodin-8-methyl ester, aloechrysone, aloesaponol, asphodelin, bianthracene
O-glycosides: aloe emodin-11-O-rhamnoside, nataloe emodin-2-O-glucoside, aloesaponol-6-O-glucoside, aloesaponol-8-
O-glucoside, aloesaponol-O-methyl-4-O-glucoside, elgonicardine
Anthrones Aloin A and B (collectively called aloin and also often referred to as barbaloin), 5-hydroxyaloin A, 7-hydroxyaloin, 10- [3537]
hydroxyaloin B, 5-hydroxyaloin A 60 -O-acetate, 7-hydroxyaloin-60 -O-monoacetate, 10-hydroxyaloin-6-O-acetate,
homonataloin, nataloin, aloinoside, barbendol, aloe-emodinanthrone, chrysophanolanthrone, aloe emodin-10-C-
rhamnoside, 8-O-methyl-7-hydroxyaloin, 60 -O-cinnamoyl-8-O-methyl-7-hydroxyaloin, 60 -O-p-coumaroyl-7-
hydroxyaloin, 7-hydroxyaloin-40 ,60 -O- diacetate, 60 -O-cinnamoyl-5-hydroxyaloin A, microstigmin A, deacetyllittoraloin,
littoraloin, littoraloside, microdontin, homonataloside
Chromones Aloesin A-F, iso-aloeresin A & D, 7-O-methylaloesin, 7-O-methylaloesinol, 7-Omethylaloeresin A, 8-[C-B-D-[2-O-(E)- [35,37
cinnamoyl]glucopyranosyl]-2-[(R)- 2-hydroxypropyl]-7-methoxy-5-methylchromone, 8
C-glycosyl-7-Omethylaloediol, 39]
C-Glycosyl-7-O-methyl-S-aloesol, 2-acetonyl-7- hydroxy-8-(2-furanonyl)-7-hydroxy-5-methylchromone, 7-Hydroxy-2,5-
dimethylchromone, 20 -p-O-methlcoumaroylaloesin
Coumarins Feralolide and dihydroisocoumarin glycoside [39]
Pyrans and pyrones Bisbenzopyran, aloenin, aloenin aglycone, aloenin acetal, aloenin B, aloe-200 -p-O-coumaroyl ester, [34,38,40]
Alkaloids N-methyltryamine, O,N-dimethyltryamine, g -coniceine, coniine [41]
Benzene, naphthalene and Protocatechuic acid, methyl-p-coumarate, pluridone, isoeleutherol, isoeleutherol-5-O-glucoside, feroxidin, feroxidin A, [41]
furan derivatives feroxidin B, plicataloside, 5-OH-3-methylnaphto[2,3-c]furan-4(1H)-one, 3-methylnaphto[2,3-c]furan-4(9H)-one, 3-
methylnaphto[2,3-c] furan-4,9-dione
Flavonoids Naringenin, dihydroisorhamnetin, apigenin, isovitexin, isorhamnetin, daidzenin, genistein [39]
Sterols Cholesterol, campesterol, b-sitosterol, lupeol
Carbohydrates Pure mannan, acetylated mannan, acetylated glucomannan, glucogalactomannan, galactan, galactogalacturan, [4244]
arabinogalactan, Galacto glucoarabinomannan, pectic, substance, xylan, cellulose, acemannan, maloyl glucans, manose,
glucose, fucose, galactose, L-rhamnose, aldopentose
Enzymes Alkaline phosphatase, amylase, sscarboxy- peptidase, cyclooxidase, cyclooxygenase, lipase, oxidase, phosphoenolpyruvate [34]
carboxylase, superoxide dismutase
Inorganic compounds Calcium, chlorine, chromium, copper, iron, magnesium, manganese potassium, phosphorous, sodium, zinc [34]
Proteins Lectins, lectin-like substance [4548]
Vitamins B1, B2, B6, B12, C, E, b-carotene, choline, folic acid,a-tocopherol [34]
Miscellaneous Arachidonic acid,g-linolenic acid, triglicerides, triterpenoid, gibberillin, lignins, potassium sorbate, salicylic acid, uric acid

2. Nature of Aloe spp. described in ITM
Avicenna has described Aloe as follows: It is a red-yellow dried
juice obtained from different species of Aloe. It is of three varieties:
(a) Scotarian, (b) Arabian, and (c) Samanjani. Its best variety is
Scotarian with the smell of myrrh and the color of saffron. It is clear,
brittle and free from pebbles. The Arabian variety is comparatively
less yellow, lighter and not so shining. Nevertheless, it is harder
and more viscous. Samanjani variety is inferior in quality,
putrefactive in nature, heavy, light yellow in color, and less bright.
Whenever the color of Aloe changes to black it means that its
properties have decreased [6].
In all of the studied literature (Table 1), the temperament of Aloe
is described as hot and dry. In most of the studied books, Aloe is
mentioned as a strong laxative (for bile, yellow bile, and phlegm),
desiccant, fattening, soporic, warmer, relaxant, resolvent (mohal-
lel), detergent (jalli), bitter, and astringent (qabez) agent [618].
Razi and several other scientists believed that unwashed Aloe is a
much stronger laxative and washing could diminish some of its
properties [19].

3. Botany of Aloe

Aloe is a large genus with 446 species [20] that belongs to the
Xanthorrhoeaceae. A. vera (L.) Burm. f., also known as Aloe
barbadensis Mill., is the most studied species in this genus (Fig. 1)
[21]. Aloe spp. grows wildly in the tropical climates around the
world particularly South Africa, Madagascar, Arabia and the Canary
Islands. They are cultivated mainly for medicinal and decorative
purposes [20].

4. Phytochemicals

Several constituents from various phytochemical classes such

Fig. 2. A cross section illustration of Aloe leaf; A: epidermis or the outer rind
consists of multiple layers interspersed with chloroplasts; B: the outer leaf pulp
consists of vascular bundles; C: mesophyll or the inner leaf pulp consists of
parenchyma cells storing the leaf gel which contains anthraquinones, anthrones,
chromones, alkaloids, pyrans and pyrones, and coumarins [49].
as alkaloids, anthrones, chromones, avonoids, glyocoproteins,
naphthalenes and pyrones have been isolated from different Aloe
spp. (Table 2) [22]. Aloin, aloesin, aloenin, aloeresin, aloe-emodin
and chrysophanol are some examples of such bioactive com-
pounds [22]. Although many biological investigations have been
performed to reveal the active constituents of Aloe spp., it is still
762 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772

As shown in Table 3, there have been many pharmacological

studies investigating the hepato-protective effects of Aloe spp.
particularly A. vera (Table 3). In most of the performed studies,
anti-inammatory and anti-oxidative activities of Aloe have been
proposed as the main mechanisms of action followed by the anti-
brosis [52] and lipid-modifying [53] activities.
In addition to A. vera, hepato-protective activity has also been
reported for other species of the Aloe genus including A.
arborescens. In a recent systematic review covering all literature
from 1976 to 2015, preparations of A. arborescens, were reported to
be mostly active in the treatment of liver diseases particularly
cancers [23].
In addition, in some of the reviewed ITM books, it is mentioned
that the medications prepared from Aloe spp. were prescribed for
the treatment of kidney diseases [10,11,18]. Although the number
of pharmacological investigations for determining the nephropro-
tective activity of Aloe is not as much as those for hepatoprotective
effects, it seems that Aloe spp. could be regarded as potential
remedies for kidney diseases (Table 3). However, more supportive
and detailed studies are required to conrm this potential
therapeutic application.

5.2. Gastrointestinal system

Fig. 3. Activity sites of Aloe preparations according to the Islamic Traditional One of the important and most cited applications of Aloe in ITM
Medicine books.
is its use in gastrointestinal problems. Aloe was thought to be
useful for the stomach; its preparations were prescribed for
not yet completely clear which compounds are responsible for the
cleansing (purgation) of the stomach from excreta (harmful
various observed pharmacological properties. However, polysac-
humors), and for the treatment of various disorders of this organ
charide and glycoprotein (lectin) fractions of Aloe spp. have been
[717,19,51]. In fact, Aloe was used as a strong laxative for cleaning
reported to possess considerable bioactivity [23,24]. Currently, two
the stomach from the superuous bilious and phlegmatic matters,
products of Aloe spp., mainly from A. vera, are produced and used:
infections and noxious humors [19,8]. In several studied ITM
Aloe gel which is derived from the succulent leaves of the plant, and
books, oral administration of Aloe with lukewarm water is
a bitter and yellow latex called aloe juice that is obtained from the
prescribed as a laxative and cleansing agent for the stomach
peripheral bundle sheath cells. Aloe gel is widely used in cosmetics,
[7,17,51]. Razi, in his book (Alhawi), together with several other
medicinal products and food supplements, and polysaccharides
scientists such as Jorjani and Ibn al-Baytar recommended Aloe
are its major constituents. Linear chains of glucose and mannose
preparations as the best remedy for the treatment of stomach
molecules, ranging in size from a few to several thousands of
disorders [7,17,19,51], because it prevents spoiling of food in the
residues, form the polysaccharides. Due to the predominance of
stomach. For this purpose, a few pills of Aloe were suggested to be
mannose to glucose, these polysaccharides are referred to as
taken in the morning and evening. Another mentioned effect of
polymannans. About 98.5% of the pulp and 99.5% of the gel or
Aloe in ITM books is restoration of the lost appetite [6].
mucilage content is water, the remaining 0.51.0% ingredients
Suggested dosage form of Aloe for the treatment of stomach
include over 75 various compounds such as polysaccharides,
problems was usually powder; Ibn al-Baytar believed that a
anthraquinones/anthrones, carbohydrates, chromones, phenolic
preparation made with pulverized Aloe is more effective in
compounds, minerals, enzymes, water-soluble and fat-soluble
cleaning the stomach because of increased contact surface and
vitamins, minerals, proteins and organic acids (Fig. 2) [24,25]. The
afnity to the stomach villus, and higher remaining time in the
presence of compounds produced via the isoprenoid pathway such
organ [7].
as carotenoids, steroids, terpenes and phytosterols has also been
In addition to laxative properties, Aloe could strengthen the
reported in this genus [2629]. Alkaloids, especially the ones
stomach and was traditionally used as a carminative and appetizer
belonging to the hemlock class, have been reported in some toxic
agent [7,10,19]. It has also been suggested for relieving the stomach
species such as A. sabaea [30,31].
pain [18].
Benecial and therapeutic effects of Aloe on the intestinal tract
5. Medicinal uses of Aloe spp. in ITM
are well accepted in ITM. Diseases such as hemorrhoids,
helminthic infections, atus, and anal ssure have been treated
In the present study, the properties of Aloe spp. are categorized
by different preparations of these plants [68,10,18,19]. Razi has
according to the organs or systems in the body on which they exert
written in Alhawi: dissolving Aloe in sweet wine is a good remedy
their effects (Fig. 3).
for hemorrhoids and anal ssure and stops the bleeding of
hemorrhoids [19].
5.1. Liver and kidney
Another important medicinal use of Aloe in intestinal diseases is
treating constipation and cleansing the intestinal tract, effects that
In several ITM books, Aloe is described as a hepato-protective
are frequently mentioned in ITM texts [7,19,51]. Administration of
agent because of its strong laxative and bile purgative effects
some Aloe pills together with honey or wine twice a day acts as a
[6,7,9,1117,50]. It is suggested that Aloe can treat obstructions of
purgative [6]. Aloe was also used to treat intestinal swelling and
the liver and jaundice, and is a liver cleansing agent [8,10,17,19,51].
inammation. For this latter purpose, it should be soaked in water
According to Jorjani, a mixture of Aloe with pure honey is a laxative
and then applied on the area [8].
of bile and treats jaundice [17,51].
 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772 763

Table 3
Hepatoprotective and nephroprotective activities of Aloe in in vitro and in vivo studies.

Activity/disease Aloe spp. Active constituents/ Study design Results Ref.

Preparations
Acetaminophen and A. vera A standardized blend comprised of Mouse model; 250400 mg/ An effective hepatic-detoxication agent for the [54]
carbon three extracts including, Aloe extracts kg; 48, 24, and 2 h before protection from liver damage
tetrachloride induction and 6 h after
induced acute liver induction
toxicities
Acetaminophen- A. vera Gel Mouse model; 150 mg/kg; It could attenuate hepatitis through the [55]
induced hepatitis orally improvement of liver histopathology by decreased
oxidative stress, reduced liver injury, and restored
hepatic GSH
Chronic alcohol- A. vera Aloe polysaccharides Mouse model; 10 and 30 mg/ A potent protective agent through antioxidant [56]
induced kg; intragastrically; twice a activity and the ability to accelerate lipolysis and
hepatotoxicity day for 11 weeks inhibit inammatory response
Ethanol-induced A. vera Gel extract Mouse model; pre-treatment Prevention of fatty liver by suppressing the mRNA [53]
hepatic lipid with 1 mg/kg/day for one expression of lipogenic genes in the liver
accumulation week
Diabetes-induced A. vera Ethanol extract Streptozotocin induced Decrease the histology of liver and kidney [57]
hepatic and renal diabetic rats; orally; 300 mg/
injuries kg for 30 days
Carbon A. vera Aqueous extract of Aloe in combination Rat model; 60 mg/kg for Improving the liver enzyme activities, antioxidant [58]
tetrachloride- with Azadirachta indica and Moringa 36 days blood parameters, and the liver histopathological
induced oleifera extracts picture
hepatotoxicity
Alcohol-induced A. vera Phytosterol lophenol and cycloartanol Rat model, 1 ml of each Decrease the expression levels of hepatic genes [59]
hepatic damage solution of Aloe sterols (25 mg/ encoding gluconeogenic enzymes (G6 Pase,
kg/day) once a day for 44; oral PEPCK), lipogenic enzymes (ACC, FAS), and SREBP-
administration 1
Alloxan-induced A. Aqueous gel extract Rat model; a daily dose of This extract could protect pancreatic beta cells [60]
Hepatic injury arborescens 300 mg/kg for 3 weeks; oral from damage by modulating key hepatic enzymes
administration
Radiation-induced A. Vera Aqueous leaf extract Mouse model; 1000 mg/kg for Increase the glutathione, acid phosphatase and [61]
Hepatic damage 15 consecutive days; oral alkaline phosphatase accompanied by a decline in
administration lipid peroxidation
Hepatic cholesterol A. vera 1% freeze-dried Aloe let; 1% Charcoal- Rat model, oral administration Prevent lipid peroxidation; [62]
and oxidative processed, freeze-dried Aloe let; a Reduce levels of hepatic phosphatidylcholine
status charcoal-processed freeze-dried, whole hydroperoxide;
leaf Aloe (0.02%) Enhance superoxide dismutase and catalase
activity
Acetaminophen- A. vera Gel Mouse model; 150 mg/kg Decrease oxidative stress, reduced liver injury, and [55]
induced hepatitis orally restored hepatic GSH
Hepatic brosis A. Aloe with honey and distillate Rat models, orally, May have immunomodulatory effects and lower [63]
arborescens, the brogenic process in the liver
Gentamicin-induced A. vera Ethanol extract of leaves Rat model; a dose of 20 ml/kg/ Prevent elevation of the biochemical indicators of [64]
nephrotoxicity day orally nephrotoxicity and signicantly reduce
histopathological scores
Gentamicin-induced A. vera Aqueous extract Rat model; 300 mg/kg orally Signicant protection of the renal cells and [65]
tubular toxicity for 10 days reduction in the severity of tubular damage
Gentamicin and A. Aqueous leaf extract Rat model; pretreatment with Attenuate elevations in the serum creatinine, total [66]
Cisplatin-induced barbadensis 100200 mg/kg/d 1 h before protein and blood urea nitrogen levels and no
nephrotoxicity each dose of the treatment related effect on uric acid and ions, and
Nephrotoxicants attenuated the gentamicin-induced
tubulonephrosis

Although Aloe was known as a good remedy for the treatment of
hemorrhoids and anal disorders, it was prohibited in some cases.
Aloe opens the rectal veins through its deobstuent activity and
some ITM scientists believed that in extreme cold and heat, Aloe
preparations were not only not benecial for the treatment of
hemorrhoids and anal ssure, but also were harmful [7,51]. They
believed that in hot and cold seasons, treatment with Aloe causes
excessive bleeding and worsens hemorrhoids due to opening the
anal veins [7]. Avicenna believed that administration of Aloe in cold
seasons may cause hemorrhagic diarrhea [6].
In ITM, Aloe was often used in combination with other
correctives for the treatment of intestinal diseases particularly
rectal problems. Ibn al-Baytar has written in his book (Al-Jamee Le-
Mofradaat al- Adwiah val- Aghziyah): Aloe should not be used as a
simple drug for the treatment of anal disorders because its
temperament is dry in second grade. On the other hand, anus is an
organ full of nerves with dry temperament. Therefore, the dryness
of Aloe causes extreme dryness in the anus and may lead to
injuries [7]. For this reason, Aloe was prescribed in combination
with other medicinal plants such as rose, Terminalia citrina Roxb,
Commiphora mukul Engl, and Pistacia lentiscus L. as correctives and
antidotes. Antaki has mentioned that administration of Aloe
together with Allium roseum L. and slough (skin of snake) is useful
for the treatment of hemorrhoids [10].
Clinical and experimental studies have shown that administra-
tion of Aloe preparations is useful for a wide range of gastrointes-
tinal problems (Tables 4 and 10). Aloe extract and a number of its
compounds have been shown to ameliorate inammation and
764 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772

Table 4
Gastrointestinal protective activities of Aloe in in vitro and in vivo studies.

Activity/ Aloe Active constituents/ Study design Results Ref.

disease spp. preparations
Colitis A. Crude extract Chicken model; 100 mg/kg orally Signicant improvement in the clinical and histopathological severity [70]
vera of the colitis
Colitis A. Aloe components Rat model; 0.005%, 0.05%, and 0.1% aloin Amelioration in the intestinal inammatory responses; aloesin was [71]
vera
including, aloin, aloesin and aloesin diets, 0.5%, 1%, and 2% aloe-gel the most potent inhibitor
and aloe-gel diets for 1 week
Ulcerative A. Aqueous extract Rat model; 200 mg/kg treatment for Reduction in the severity of symptoms of ulcerative colitis [72]
colitis vera 8 days histopathology
Constipation A. Aqueous extract Rat model; 50, 100 and 200 mg/kg/day for A potent laxative agent [73]
ferox 7 days
Intestinal A. Gel supercritical CO2 Mouse model; 3.75 and 12.5 mg/kg oral Reduction in large-sized intestinal polyps and ameliorated reduction [74]
polyp vera extract containing ve administration daily for 7 weeks in plasma HMW adiponectin levels
formation phytosterols
Irritable A. A mixture of Aloe and Rat model, 50: 50 at doses of 150, 300 or A potential remedy [75]
bowel vera Matricaria recutita 450 mg/kg, intragastrically by gavage for
syndrome 7 days
Prebiotic A. Aloe mucilage In vitro fermentation using intestinal A bioactive ingredient in the formulation of novel functional foods [76]
activity vera containing microbiota from six healthy donors as the
polysaccharides inoculum
Peptic ulcer A. Aloe juice in Rat model; 20.0 ml/kg for 22 days Content of haemoglobin and RBC and WBC counts were brought back [77]
vera combination with to normalcy after the treatment. The plant juices are having efciency
papaya fruit juice in the gastroprotective activity
Peptic ulcer A. Aloe powder mixed Rat model, 200 mg/kg, orally Signicant anti-ulcer activity [78]
vera with gum acacia

Table 5
Upper respiratory protective activities of Aloe in in vitro and in vivo studies.

Activity/ Aloe spp. Active constituents/ Study design Results Ref.

disease Preparations
Infections of A. Bioaron C1, an herbal In vitro: a broad panel of Effective against the orthomyxoviridae, inuenza A and inuenza [80]
the upper arborescens medicinal product consisting of viruses involved in upper B, viruses and non-enveloped RNA viruses belonging to the family
respiratory an aqueous extract of Aloe respiratory tract infections of picornaviridae; No antiviral activity against adenovirus; poorly
tract active against syncytial virus and parainuenza virus belonging to
the paramyxoviridae
Cigarette A. vera Aloe gel extract Mouse model; 500 mg/kg A potential agent for modulating cigarette induced changes in the [81]
induced daily for seven weeks pulmonary tissue
pulmonary
tissue injury
Adult Aloe polysaccharide and In vitro: Leukocytes from Effective through improvement peripheral phagocytosis [79]
bronchial glycoprotein fractions peripheral blood of patients
asthma
Oral wound A. vera Hydroalcoholic extract of Aloe Rat model; topical No signicant difference was observed in treated and untreated [82]
healing administration twice a day for groups
14 consecutive day

improve clinical and histopathological symptoms of colitis in
animal models. Moreover, a combinational herbal preparation
containing Aloe has been reported to improve irritable bowel
syndrome symptoms in rats. Signicant anti-ulcer and gastro-
protective activity were also observed after administration of
compound preparations containing Aloe. Interestingly, as frequent-
ly mentioned in ITM texts, aqueous extract of Aloe exhibits a potent
laxative activity. In addition to the activities reported in Tables 3
and 10, Aloe is thought to be a potential agent in the treatment of
gastrointestinal cancers [6769]. Despite special emphasis of ITM
on the anti-hemorrhoid effects of Aloe, pharmacological data
supporting this activity are scarce.

Table 6
Protective activities of Aloe on genital organs in in vitro and in vivo studies.

Activity Aloe Active constituents/ Study design Results Ref.

Sexually transmitted
infections: Herpes simplex
virus type 1 and 2
Herpes simplex virus type 2
spp. preparations
A. Aqueous extracts from Aloe and In vitro: Vero African green monkey cell A useful treatment for sexually [83]
ferox Withania somnifera, together with cultures; 1000 mg/ml for extracts and 62 mg/ transmitted infections
aloin ml for aloin
A. A crude hot glycerine extract In vitro: Vero (African green monkey kidney) A good candidate as a natural source [84]
vera cell line for antiviral drug development against
HSV-2
 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772 765

Table 7
Protective activities of Aloe on central and peripheral nervous systems in in vitro and in vivo studies.

Activity/disease Spp. Preparation Study design Result Ref.

Sedative and A. vera Aqueous extract Rat model; 50, 100, 200 mg/kg The extract showed sedative-hypnotic effects on both functional [92]
hypnotic effects intraperitoneal injection and electrical activities of the brain
Analgesic activity A. perryi Ethanolic extract Mouse & rat model; 100 and 250 mg/ No central morphine-like analgesic activity, signicant peripheral [93]
of leaves juice kg orally analgesic action
Parkinson's disease A. vera Aqueous extract Mouse model; 200 and 400 mg/kg, p. A potential anti-parkinson effect in mice; signicant anti- [90]
of Aloe gel o. oxidative effect in the striatal region of the brain, minimal
neuronal destruction
Memory A. vera A leaf gel extract Mouse model; 200 and 400 mg/kg, p. Increase learning and memory, decrease depression [85]
improvement and o.
anti-depression
Epilepsy A. vera Aqueous extract Mouse model, 100, 200 and 400 mg/ Signicant anticonvulsant and anti-oxidant activity [91]
of Aloe leaf kg p.o
powder
Learning and A. vera Aloe-emodin Mouse model A signicant improvement in the learning and memory ability [86]
memory functions
Cerebral ischemia Aloe Rat model; 60 mg/kg for 7 days by A protective effect on cerebral ischemia via inhibiting caspase-3 [94]
and reperfusion polysaccharides gavage expression
injury
Neuroprotective A. vera Aloe extract In vitro: rat pheochromocytoma Improvement in the mitochondrial damage; protection the [87]
activity (PC12) cells and rat brain, 1 and 10 mg structure and function of mitochondria in rat brain
x L(-1)
Cognitive decits Aloe-emodin Mouse model; 25, 50 and 100 mg/kg A signicant improvement in cognitive decit [88]
p.o. daily for 15 days
Alzheimer's disease A. Aloe extract In vitro: IMR32, a neuroblastoma A potent agent [89]
arborescens human cellular line
Ischemia A. vera Gel Rat model; 30 mg/kg/day via gastric A neuroprotective agent against sciatic nerve ischemia/ [95]
Reperfusion injury gavage for 1 month reperfusion injury via antioxidant and anti-inammatory
of sciatic nerve properties

5.3. Upper respiratory tract
The benecial properties of Aloe for the treatment of respiratory
diseases especially asthma have been described by many ITM
scientists such as Ibn al-Baytar, Hakim Momen, Antaki, and Aqili
Alavi [7,912,14,15,18]. They prescribed Aloe for the treatment of
lung bleeding and cleansing the lungs and throat from harmful
humors [7,11,1719]. Ibn al-Baytar has mentioned that repeated
inhalation of the burned Aloe smoke is one of the best remedies for
the treatment of asthma [7]. Aloe was also prescribed for mouth,
nose, tongue, and gum diseases [7,18,19]. Polysaccharides and
glycoprotein fractions of Aloe have been found to improve
peripheral phagocytosis in the blood of patients with bronchial
asthma [79], thus supporting ITM uses of Aloe as an effective anti-
asthmatic remedy. Aloe also exhibits antiviral activities against a
number of viruses involved in upper respiratory tract infections in

Table 8
Skin protective activities of Aloe in in vitro and in vivo studies.

Activity/ Spp. Preparation Study design Result Ref.

disease
Wound A. vera Aloe pulp Rat model A signicant improvement healing in the burning wounds [102]
healing
Wound A. vera Mannose rich Aloe polysaccharides Rat model; topical The extract could improve wound healing through induction of [103]
healing administration 25 and 50 mg MMP-3 and TIMP-2 gene expression
daily for 30 days
Antibacterial A. vera Aloe essential oil extract In vitro: multi-drug resistance Signicant anti-staphylococcal activity [96]
activity Staphylococcus
aureus specimen isolated
from patients with skin
infections; 0.8 gm/100 ml
Antibacterial A. vera Aloe essential oil extract Mouse model, for 7 days Remarkable anti-staphylococcal activity [96]
activity
Atopic A. vera Gel Mouse model; topical Although both gels could inhibit the cutaneous inammatory [104]
dermatitis and A. administration; for 10 responses, the gel of A. ferox was more potent; they may be an
ferox consecutive days alternative to antihistamines and topical corticosteroids
Burn wound A. vera Aloe emodin from Aloe in Mouse mode; 1, 100 and A signicant increase in wound healing activity; increase in the [97]
healing combination with resveratrol 500 ng/ml for 7 days levels of IL-1b
Skin wound A. vera Mannose rich Aloe polysaccharides Rat model; 25 mg and 50 mg Positive effects on the regulation of extracellular matrix [105]
repair for 30 day
Wound A. Raw mucilaginous gel and two gel Rat model; 500 mg once daily A potential wound-healing and anti-inammatory agent [98]
healing littoralis formulations prepared from the for 24 days
raw mucilaginous gel
Wound A. vera Aloe gel Rat model; 50% and 96.4% A signicant increase in collagen content [106]
healing preparations of gel
766 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772

Table 9
Eye protective activities of Aloe in in vitro and in vivo studies.

Activity/disease Spp. Preparation Study design Result Ref.

Re-epithelialization of A. Aloe gel eye drops Rat model; a single drop (0.05 ml) to the Enhanced corneal re-epithelialization; reduced [107]
corneal alkali burn vera central cornea of the injured eye four times inammatory response
daily for 3 days
Histomorphometric A. Gel extract Rat model; 400 mg/kg for 12 and 16 weeks, Long-term treatment of the gel extract could affect the [109]
alterations in the vera once daily degenerated retina and the thickness of different layers
diabetic retina of diabetic retina
Anti-inammatory A. Ethanol, ethyl acetate and In vitro: culture of human 10.014 pRSV-T Ethanol and ethyl acetate extracts may be used to treat [110]
activity on corneal vera heptane extracts of Aloe corneal cells inammations and other ailments of external parts of
cells the eye such as the cornea
Ultraviolet light A. A binary solution of Aloin The phenolic chromophores pertaining to aloin have UV [111]
absorption vera and polysaccharide rich light protective activity
extracts
Apoptosis of retinal Aloe-emodin In vitro: primary cultures of corneal Aloe-emodin can suppress NMDA-induced apoptosis of [108]
ganglion cells epithelial cells; 0.02 mg/ml retinal ganglion cells through regulation of ERK
phosphorylation
Corneal wound A. Aloe gel solution In vitro: primary cultures of corneal Benecial in healing of supercial corneal wounds to [112]
closure vera epithelial cells, 0.02 mg/ml help decrease
brosis and speed epithelialization

vitro [80]. Moreover, Aloe gel extract could recover cigarette-
induced changes in the pulmonary tissue [81]. Further pharmaco-
logical investigations and clinical trials will improve our under-
standing of the protective respiratory activities of Aloe and its
components along with pharmacokinetic, dosage and toxicity
aspects of this plant (Table 5).
5.4. Reproductive (genital) organs
Aloe has also been reported to be useful for the treatment of
male and female genito-urinary system diseases particularly
genital ulcers and lesions [7,8,11,17,19]. For this purpose, Aloe is
rst dissolved in water and then applied on the organ skin [19].
Interestingly, Aloe extract has been found to exhibit antiviral
effects against Herpex simplex virus type 1 and 2 [83,84], a nding
that supports its traditional application in the treatment of genital
ulcers and infections (Table 6).
5.5. Central and peripheral nervous systems
In most of the ITM books that were investigated, Aloe was
believed to be useful for cleaning the brain from waste humors
including yellow bile, phlegm, and infections, as well as for
warming the brain. ITM scientists believed that Aloe is a desiccant
agent for washing out the extra moisture of the brain and nerves
[69,1119]. Due to this property, different ailments of the brain
were treated with Aloe preparations. Aloe was used for the
treatment of melancholy, schizophrenia, obsession, insanity and
headache, and also for enhancing the intelligence, strengthening
the memory, and disturbed sleep [7,11,18]. Topical administration
of Aloe by rubbing on frontal and temporal areas was thought to
alleviate headache; for this purpose, Jorjani and Razi prescribed it
in combination with vinegar and rose oil. The hypnotic properties
of Aloe have also been mentioned in some texts [18]. Due to its
effects on warming the brain, Aloe was suggested as a good remedy
to stop catarrh [7]. Ibn al-Baytar has written: putting Aloe along
with salt and natron on the anterior part of the head stops catarrh.
Table 7 shows the pharmacological activities of Aloe on central and
peripheral nervous systems. As shown in Table 7, Aloe extracts and
their components have numerous CNS activities such as hypnotic,
peripheral analgesic and neuroprotective activities. Moreover,
many pharmacological studies have reported improvements in
learning, memory and cognitive function and Alzheimer disease
following administration of Aloe extracts as indicated in ITM
textbooks [8589]. A potential anti-Parkinson's activity has also
been reported for Aloe gel in mice [90]. Moreover, aqueous extract
of Aloe leaf powder exhibited anticonvulsant properties in mice
[91]. Aloe-emodin and Aloe polysaccharides seem to be the main
neuroactive principles of Aloe which deserve further investigations
in order to develop new CNS protective agents for the treatment of
a wide spectrum of CNS ailments.
5.6. Skin
Aloe preparations were used for an extensive range of skin
disorders ranging from infectious problems to allergic reactions.
Aloe was often prescribed for the treatment of different types of
wounds and injuries including deep injuries, malignant lesions,
corroding ulcers, bruises etc. As mentioned, not only Aloe
preparations were not only used for the treatment of microbial

Table 10
Hair protective activities of Aloe in in vitro and in vivo studies.

Activity Spp. Preparation Study Result Ref.

design
Hair growth A. A mixture of hydrophilic substances of Aloe gel and Rat model The mixture in nano-size globules of water in oil and oil in water [113]
promotion vera semipolar substances of Apium graveolens microemulsions lead to pilosebaceous targeting and optimize the growth
ethanolic extract promotion activities
Hair A. Aloe fresh and processed juice Different Both preparations were photo protective however the fresh juice was [114]
protective vera Asian hair more effective
effect type
against UV
 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772 767

Table 11
Clinical trials related to reported properties of Aloe in ITM.

No. Activity/disease Aloe spp. Active Study design Dose Participants Description Ref.
constituents/
preparations
1 Cesarean wound healing A. vera Gel A randomized Ninety women; mean Positive effects of dressing with [119]
controlled age: 27.56  4.20 A. vera gel
clinical trial
2 Radiation induced A. vera A A self- From week 4 to Sixty patients; mean The prophylactic use of A. vera [120]
dermatitis commercially- controlled week 2 of age: 52 years; 67% reduces the intensity of
available lotion clinical trial radiotherapy and women; twice a day irradiation-induced dermatitis
then at weeks 2 for 2 weeks
and 4 after
radiotherapy
3 Chronic skin lesions A. vera A. vera/olive oil A randomized Twice daily for 6 Sixty seven Iranian As effective as betamethasone [121]
following sulfur cream double-blind weeks chemical warfare- 0.1%
mustard exposure clinical trial injured veterans
4 Mild to moderate plaque A. vera Cream A randomized, Eight weeks Eighty patients May be more effective than 0.1% [122]
psoriasis comparative, triamcinolone acetonide
double-blind
5 Anti-irritant effect A. vera Gel Concentrations of Fifteen patients over An effect in the recovery of skin [123]
10, 20, 50, and 18 years barriers and erythema induced
100% for 24 h by irritant such as sodium lauryl
sulfate at high concentrations
6 Diaper dermatitis in A. vera Aloe cream (in A randomized Three times a day Sixty-six infants with A safe and effective treatment [100]
children and infants combination and double- for 10 days diaper dermatitis with no adverse effects
with Calendula blind trial (aged 3 years)
ofcinalis
ointment)
7 Radiation-induced skin A. vera Quality-tested Three-Arm For 1, 2, and 4 Two hundred and No improvement in the [124]
injury Aloe extract Randomized weeks forty eight patients symptoms or reduction in the
Phase III Trial with breast cancer skin reaction severity
8 Slight to moderate A. vera A commercial, A randomized Twice a day for 4 Forty-one patients Modest activity [125]
psoriasis vulgaris preserved gel double-blind, weeks with stable plaque
placebo- psoriasis
controlled
study
9 Dry skin conditions A. vera Aloe sterols A randomized, Five tablets per day Fifty eight Japanese Stimulation of collagen and [126]
(cycloartenol double-blind, each containing women aged 40 hyaluronic acid production by
and lophenol) placebo- 40 mg Aloe sterols, years human dermal broblasts
controlled trial orally for 8 weeks
10 Psoriasis vulgaris A. vera Aloe extract A placebo- Topically, 3 times a Sixty patients (mean A safe and alternative treatment [127]
0.5% in a controlled, day for 5 25.6) to cure patients suffering from
hydrophilic double-blind consecutive days psoriasis without adverse effects
cream study
11 Skin damage by A. vera Aloe A prospective For one year One hundred and None [128]
radiation polysaccharides self-control eighty ve newly
study diagnosed
nasopharyngeal
carcinoma patients
12 Scabies A. vera Crude gel An open, non- Daily for 4 weeks Thirty patients As effective as benzyl benzoate [129]
comparative
study
13 Acne vulgaris A. vera Aloe topical gel A randomized, For 8-week Sixty subjects with signicant improvement in mild [130]
(50%) with double-blind, mild to moderate to moderate acne vulgaris
tretinoin and prospective acne vulgaris
vehicle trial
14 Chronic anal ssure A. vera Topical cream A prospective Three times per Aged 2070 years Statistically signicant [131]
pain, wound healing and containing 0.5% double blind day for 6 weeks differences in chronic anal
hemorrhaging upon Aloe juice clinical trial ssure pain, hemorrhaging upon
defection powder defection and wound healing
(p < 0.0001)
15 Posthemorrhoidectomy A. vera Cream A randomized, Three times per Forty-nine patients Effective in reducing [132]
pain and wound healing blind, placebo- day for 4 weeks postoperative pain both on
control study after resting and during defecation,
hemorrhoidectomy healing time
16 Refractory irritable A. vera Aloe juice A trial Thirty ml twice Thirty three patients Reduce abdominal pain/ [133]
bowel syndrome daily for 8 week with constipation- discomfort and decrease
predominated atulence, but unable to
refractoryirritable improve urgency and frequency
bowel syndrome as well as consistency of stool
17 Ulcerative colitis A. vera Aloe gel A randomized, One hundred ml Forty ve evaluable Reduction in the histological [134]
double-blind, twice daily for 4 hospital out-patients disease activity without no
placebo- weeks signicant adverse effect
controlled trial
18 Irritable bowel A. Aloe extract A randomized, Tablets containing Sixty eight adults A promising treatment for this [135]
syndrome barbadensis double-blind, 250 mg Aloe extract aged 1865 years purpose
placebo- twice a day
controlled trial
768 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772

Table 11 (Continued)
No. Activity/disease Aloe spp. Active Study design Dose Participants Description Ref.
constituents/
preparations
19 Gingivitis A. vera A commercially A randomized For 6, 12, and 24 Ninety patients Signicant improvement in [136]
available controlled weeks diagnosed with gingival and plaque index scores
dentifrice clinical trial chronic generalized as well as microbiologic counts
containing A. gingivitis; aged 25 to compared with placebo
vera 40 years dentifrice
20 Oral lichen planus A. vera Aloe A randomized For 4 weeks Forty six patients Effective as much as [137]
Mouthwash double- triamcinolone acetonide 0.1%
blinded
clinical trial
21 Oral sub-mucous A. vera Gel Preliminary Five g, topical, Twenty study Reduction in the burning [138]
brosis study three times daily subjects with oral sensation and
for 3 months sub-mucous brosis improvement in mouth opening
thereby
22 Plaque and gingivitis A. vera A dentifrice A randomized, Three times a day, Fifteen male and 15 There was a signicant reduction [139]
containing Aloe parallel and during a 30-day female, aged 35 to 43 on plaque and gingivitis in both
double-blind period years control and Aloe group, but no
clinical trial statistically signicant activity
(p > 0.01)
23 Plaque and gingivitis A. vera A toothpaste A randomized, For three 6-month Fifteen subjects A statistically and clinically [140]
containing high double-blind, periods signicant reduction of about
concentrations intra- 20% of the plaque and gingivitis
of Aloe individual and indices at the end but no
controlled differences between the A. vera
clinical study and the control toothpaste
24 Burning mouth A. vera Tongue Prospective, Three times a day Seventy ve patients The concomitant prescription of [141]
syndrome protector and randomized, for 3 months with burning mouth tongue protector and Aloe is
0.5 ml A. vera double-blind, syndrome effective for treating patients
clinical
evaluation
25 Oral aphthous A. vera Acemannan, a 0.5% acemannan in One hundred and A signicant activity but not as [142]
ulceration polysaccharide Carbopol1 934P NF eighty subjects with much as 0.1% triamcinolone
extracted from (Lubrizol recurrent aphthous acetonide
A. vera Corporation, USA), ulceration and 100
3 times a day for healthy subjects as a
7 days control group
26 Acute viral hepatitis A. vera Juice A prospective, twenty ml BD One hundred and ten A statistically signicant [143]
randomized, orally, 6 weeks male and female (p < 0.001) decrease in Serum
open, parallel patients of age group bilirubin, serum Alanine
group, between 15- 65 years transaminase, serum Aspartate
interventional transaminase and serum
study Alkaline phosphatase levels
27 Hepatic periportal A. vera High molecular Oral Forty patients and A signicant amelioration in [144]
brosis weight administration; Fifteen healthy brosis, decrease in
fractions 0.15 gm/d, for 12 volunteers as a inammation, decrease in the
consecutive weeks control group activities of the liver enzymes, a
signicant reduction in the MDA
levels, decrease in the hepatic
glutathione content, a signicant
reduction in the brosis markers
28 Hepatoprotective A. vera Extracts Clinical Intraperitoneal Effective in lowering the [117]
activity practice administration; elevated sGPT in subjects
1015 ml/kg/d, ip x suffering chronic hepatitis with
4 positive HBsAg
29 Anti-brotic effects A. vera High molecular Clinical Patients with HCV, This activity could be attributed [52]
weight practice HBV and bilharziasis to the ability to attenuate
fractions oxidative stress, and enhance the
collagenolytic activity
30 Wound healing of A. vera Ointment A randomized Every 8 h for 5 days, 74 primiparous A signicant activity observed [145]
episiotomy control trial topical women
31 Vulval lichen planus A. vera Gel Randomized, For 8 weeks Thirty-four female A safe and effective treatment [146]
double-blind, patients for patients with vulval lichen
placebo- planus without side effects
controlled trial
32 Genital herpes in men A. vera A hydrophilic A placebo- Three times daily Sixty patients aged An alternative, reliable and [147]
cream controlled for 5 consecutive 1840 years (mean effective treatment to cure the
containing 0.5% double-blind days, topical 23.6), with culture- rst episodes of genital herpes in
Aloe extract study conrmed diagnosis men
of herpes simplex
genitalis
33 Alzheimer Aloe An open-label Four teaspoons per Adults diagnosed Clinically-signicant [148]
polymannose trial day for 12 months with alzheimer improvement
multinutrient disease
complex
35 Ocular surface A. vera Eye drops Human study, Three times daily [149]
squamous neoplasia case report for 3 months
 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772
Table 11 (Continued)
No. Activity/disease Aloe spp. Active Study design
constituents/
preparations
and parasitic skin disorders such as scabies, herpes simplex, and
Saint Anthonys re, but also they were administered for allergic
skin problems including urticaria and itching [6,814,17,18,50,51].
Aloe was also used as a moisturizing agent on the skin of hands and
face [19]. According to the studied texts, ITM scientists believed
that Aloe could exert its benecial effects on skin disorders through
drying the skin and preventing proliferation and spreading of
lesions.
The effects of Aloe on skin and its wound healing activity have
been studied extremely in modern medicine (Tables 8 and 10).
Anti-microbial, antioxidant, and anti-inammatory activities are
among the main mechanisms through which Aloe exerts its skin
protective activities [96101].
5.7. Eyes
The benets of Aloe preparations, particularly as kohl, for the
treatment of ocular problems have been reported in all ITM books
studied [710,1219,51]. It is useful in ocular ulcers, pain, swelling
and irritation of the canthus. It also dries up the moisture of the
canthus [6]. Treatment of ocular wounds, stopping ocular bleeding,
washing out harmful infectious moisture of the eyes, strengthen-
ing the eyesight, treatment of cataracts, and improving the
thickness of eyelids are other properties of Aloe mentioned in
ITM books. Aloe was also used for the treatment of belpharitis
which is an ailment of retina [10]. The combination of Aloe with
honey is a good remedy for bruises around the eyes [19].
In an experimental study, administration of an eye drop
containing Aloe gel enhanced corneal re-epithelialization in rats
with injured eyes [107]. Aloe-emodin could suppress NMDA-
induced apoptosis of retinal ganglion cells suggesting its possible
role in the treatment of glaucoma [108] (Table 9).
5.8. Joints and muscles
Aloe possesses anti-inammatory properties and used to cure
joint problems such as arthralgia [6]. In addition, it was used in
medications for the therapy of fatigue, bruises, joint dislocation,
gout, and fractures [7,913,15,1719]. No exploratory study has yet
been performed to verify the traditional applications of Aloe in the
treatment of joint problems.
5.9. Hair
One of the mentioned effects of Aloe in ITM is its potent activity
on hair growth and treatment of microbial diseases of the hair. Aloe
was used for the prevention of hair loss, hair strengthening,
blackening of the hair, removing dandruff, and lice removal [6
8,1017]. It was also used as a therapy for different types of alopecia
including alopecia areata and favus. Several preparations of Aloe
were used for the mentioned purposes. For instance, washing hair
with Aloe and wine or Ruta graveolens L. was prescribed for the
treatment of hair loss, hair strengthening, hair growth, and
prevention of hair graying [10,19].
One of the most frequent uses of Aloe in modern medicine is its
application in cosmetic products such as night creams, soaps,
shampoos, suntan lotions, and cleansers. There are various
769
Dose Participants Description Ref.
The patient remained tumor free
for 6 years without additional
topical medications
preparations and products from Aloe for beauty and health of
hair in the pharmaceutical markets. Pharmacological studies have
revealed that administration of nano-size globules of micro-
emulsions containing a mixture of hydrophilic substances of Aloe
gel and semipolar substances of Apium graveolens ethanolic extract
improves hair growth in vivo [113].
6. Toxicity and safety studies
Although natural products and plants are a good candidate to
cure human diseases, it should be considered that they are not as
safe as the public thinks, and may cause problems in long-term use.
Aloe is not an exception in this regard. Some species of this genus
such as A. ferox are potentially toxic. Generally, Aloe is considered
as an almost safe remedy in ITM. Nevertheless, toxicity of Aloe on
liver has been mentioned by several ITM scientists. For instance,
Ibn Sina has declared that although Aloe can open obstructions of
the liver, it can be harmful at high doses or in long-term use [6].
This toxicity has been conrmed in some investigations including
human studies [115,116]. For example, a 21-year-old woman taking
30 ml of A. vera gel extract powder twice a day for approximately
one month was diagnosed with acute toxic hepatitis [117]. In
another study, a 57-yr-old woman taking Aloe tablets (containing
250 mg of an extract of A. arborescens and 28.5 mg of an extract of A.
vera), a 62-yr-old woman taking Aloe powder (containing 420 mg
of an extract of A. vera) for about 3 months, and a 55-yr-old woman
taking Aloe extracts for about 5 months were diagnosed with Aloe-
induced hepatotoxicity [115]. However, some in vitro and in vivo
investigations have rejected side effects of A. vera on the liver [118].
This conict may be due to investigating different preparations of
Aloe, different parts used, or various study models. Hence, further
studies are necessary to verify the potential adverse effects of Aloe
on the liver (Table 11).
7. Conclusion
Systems of traditional medicine around the world play
important roles in discovering new drugs owing to the antiquity
of their instructions, practices, skills and knowledge, and the use of
their preparations and prescriptions over generations. ITM benets
from the instructions made by several renowned scientists, and is a
pioneer and effective school in medical sciences. Hence, exploring
ITM texts could be a valuable approach for detecting new
medicines. In the current study, the applications and benecial
properties of Aloe spp. was investigated in ITM books, and
conformity of the ndings with the results reported in modern
pharmacological studies was checked. Aloin, aloesin, polysacchar-
ides, aloe-emodin and Aloe essential oil are the most biologically
active ingredients of these species. Although many pharmacologi-
cal activities of Aloe spp. have been studied recently, conducting
additional studies, particularly clinical trials, is necessary to ll
existing gaps in our knowledge of various aspects of these species.
Conict of interest
None.
770 M. Akaberi et al. / Biomedicine & Pharmacotherapy 84 (2016) 759772
Acknowledgements
The authors wish to thank Mashhad University of Medical
Sciences.
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