Accepted Manuscript

Aloe vera: ancient knowledge with new frontiers

Dalia I. Sánchez-Machado, Jaime López-Cervantes, Raquel Sendón, Ana Sanches-

Silva

PII: S0924-2244(16)30307-7
DOI: 10.1016/j.tifs.2016.12.005
Reference: TIFS 1937

To appear in: Trends in Food Science & Technology

Received Date: 22 July 2016

Revised Date: 25 November 2016
Accepted Date: 21 December 2016

Please cite this article as: Sánchez-Machado, D.I., López-Cervantes, J., Sendón, R., Sanches-Silva,
A., Aloe vera: ancient knowledge with new frontiers, Trends in Food Science & Technology (2017), doi:
10.1016/j.tifs.2016.12.005.

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 ACCEPTED MANUSCRIPT
Aloe vera:ancient knowledge with new frontiers

Dalia I. Sánchez-Machadoa; Jaime López-Cervantesa; Raquel Sendónb, Ana Sanches-

Silvac,d,*

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a
Instituto Tecnológico de Sonora, 5 de Febrero No. 818 sur, Apdo. 335, C.P. 85000 Ciudad

Obregón, Sonora, México

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b
Department of Analytical Chemistry, Nutrition and Food Science, University of Santiago de

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Compostela. Santiago de Compostela, Spain
c
Department of Food and Nutrition, National Institute of Health Dr. Ricardo Jorge, I.P., Av.

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Padre Cruz, 1649-016, Lisbon, Portugal;
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d
Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e

Agroambiente (ICETA) da Universidade do Porto, Praça Gomes Teixeira, Apartado 55142,

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4051-401, Porto, Portugal

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* Corresponding author

Ana Sanches Silva

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Department of Food and Nutrition

National Institute of Health Dr Ricardo Jorge

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Av. Padre Cruz | 1649-016 Lisboa | Portugal

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Tel.: (+351) 21 752 64 85

Fax: (+351) 21 750 81 53

e-mail: ana.silva@insa.min-saude.pt and anateress@gmail.com

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Abstract

Background: There are many plants with interesting pharmaceutical activities but Aloe

vera is probably the most applied medicinal plant worldwide. Since biblical times, aloe

has been used for its purgative effect, skin disorders healing and beauty treatments.

Scope and approach: For this study, an extensive review on Aloe vera was carried out,

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including its main uses, components (both nutrients and bioactives), biological

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activities, and applications. Future trends were also assessed.

Key findings and conclusions: Aloe possesses numerous activities including,

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anticancer, antioxidant, antimicrobial, antiallergic, anti-inflammatory,

immunomodulatory, hepatoprotective, antiulcer and antidiabetic. Some of these

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activities are due to the presence of polysaccharides (acemamman; glucomannan). A
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wide variety of commercial products based on Aloe vera are available on the market.
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However, the knowledge of the relationship between biological and therapeutic

properties and its components has to be clearly defined in order to know the exact
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mechanism of action to develop effective new products, namely pharmaceuticals. The

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knowledge of the factors that affect Aloe vera variability, such as processing conditions,

is also of great importance to be able to standardize the final products.

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Keywords: Aloe vera, composition, biological activities, processing effect..

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1. Introduction

Nowadays food, pharmaceutical and cosmetics industries look for new sources of

natural compounds with interesting properties (Carvalho-Costa et al., 2015; Ribeiro-

Santos et al., 2015). There are many plants with interesting pharmaceutical activities but

Aloe vera is probably the most applied medicinal plant worldwide. Since biblical times,

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aloe has been used for its purgative effect, skin disorders healing and beauty treatments.

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Numerous studies report that aloe leaf possesses numerous activities including,

anticancer, antioxidant, anti-inflammatory, immunomodulatory, hepatoprotective,

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antiulcer and antidiabetic (Reynolds & Dweck, 1999). Therefore, many times is called

the wonder plant. Many scientific documents have reported the application of Aloe vera

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in dermatology, to treat radiation-caused skin conditions and in gastroenterology or
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gynaecology as bactericidal, virucidal or fungicidal. The gel of the leaves is associated
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with many polysaccharides. In fact, more than 200 bioactive chemicals have been found

in Aloe vera gel (Ahlawat & Khatkar, 2011). The biological activities of aloe leaf
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extracts are more likely to be due a synergistic action of the compounds rather than a
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single compound (Hamman, 2008). The industry of the products derived from Aloe vera

(food products such as drinks with aloe, milk, ice cream, food supplements, gel
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preparations and ointments and cosmetic products such as creams, soaps, shampoos,

facial cleaners, lotions) is economically very important and it is increasing year by year.
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Therefore, the optimization of the processing (e.g. harvesting, handling, transportation,

grinding, heating, dehydration, gel expulsion, gel extraction, gel stabilization) is very

important to obtain more active and effective products and to avoid changes of

composition that may change physiological and pharmaceutical properties of Aloe vera

products (Ramachandra & Rao, 2008)

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Aloe vera gel and whole leaf extract have showed to improve the bioavailability of

vitamins. This opens a new application of Aloe vera, which can be used as excipient of

sustained-release tablet formulations (Vinson et al., 2005; Jani et al., 2007; Hamman,

2008).

The price of a product may be a guide to select a good aloe product, however the most

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important key to evaluate are the results obtained. Moreover, one can also search for the

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certification seal of the International Aloe Science Council (http://www.iasc.org/), an

international trade association of producers and marketers of Aloe vera, in the

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packaging or to look for the number of mucopolysaccharies of the product (the highest

therapeutic value is found between 10,000-20,000 mucopolysaccharies per liter) (Pal et

al., 2013).
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New products have also being developed from Aloe vera, an example are the edible
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coatings of aloe to preserve fruits such as table grape and cherry (Valverde et al., 2005;

Martínez-Romero et al., 2006; Serrano et al., 2006).

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This review aims to provide a systematic overview of the composition and main
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biological activities of Aloe vera. In addition, its main applications are also reviewed

and discussed. The assessment of future trends was also carried out.
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2. Brief history
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First historical findings regarding aloe date back to 2100 B.C. where it was mentioned

in a collection of Sumerian clay tablets. In 1552 B.C. it was mentioned as a laxative in

the Egyptian Papyrus Ebers (Manvitha & Bidya, 2014). Besides Egyptians, Roman,

Greek, Arab and Indian also recognized the healing properties of this plant (Joseph &

Raj, 2010). In fact, Discordes, a Greek physician has stated that aloe could treat

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wounds, heal skin infections, diminish hair loss and eliminate haemorrhoids in the book

De Materia Medica (Shelton, 1991).

In the 4th century B.C., Greeks found aloe in the island of Socotra in the Indian Ocean.

In fact, Alexander The Great was persuaded by his mentor Aristotle to capture this

island due to the supplies of aloe to heal his wounded soldiers. Aloe was used by

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Cleopatra (69-30 B.C.) and Nefertiti as part of their beauty treatments.

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In 1920 Aloe vera was first cultivated for pharmaceutical distribution (Shelton, 1991).

The commercial use of aloe gel started in the 50´s and in the 60´s a pharmacist called Dr

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Bill C. Coates in Dallas (Texas, USA) was succeeded in his goal of extracting the gel of

Aloe vera while preserving his healing properties. This stabilized gel opened new fields

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of application. Mexico is the main producer of Aloe vera worldwide (Pal et al., 2013).
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3. Botanical description, distribution and cultivation

According to the International Rules of Botanical Nomenclature, the scientific name for
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Aloe vera is Aloe barbadensis Mill. and Aloe vera (L.) Burm. F. is a synonym (Sahu et
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al., 2013). However it is known by other names (Aloe chinensis Bak, Aloe elongate

Murray, Aloe indica Royale, Aloe officinalis Forsk, Aloe perfoliata, Aloe rubescens DC,
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Aloe vera L. var. littoralis Konig ex Bak, Aloe vera L. var. chinensis Berger, Aloe

vulgaris Lam.) (Ahlawat & Khatkar, 2011).

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Taxonomically Aloe vera belongs to the Aloeaceae family (Table 1). This is related to

lily family including garlic and onion which is well known for their chemical properties

(Marchese et al., 2016). Aloe vera is a perennial, drought-resisting plant (resists more

than 7 years without water) with thick, tapered, green lance-shaped, juicy, basal, sharp

pointed and jagged and edged leaves (Joseph & Raj, 2010; Manvitha & Bidya, 2014).

The leaves join at the stem forming a rosette (Pal et al., 2013). It has a cactus
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appearance; therefore it is often mistakenly called “Desert Cacti”. It has also been called

medicine plant, burn plant, first aid plant, lily of the desert, elephant’s gall (Ahlawat &

Khatkar, 2011; Joseph & Raj, 2010). There are more than 350 species of Aloe, being

Aloe barbadensis Mill. and Aloe arborescens the most common (Eshun & He, 2013).

Chemically speaking, the general Aloe CAS number is 8001-97-6, whilst Aloe

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barbadensis extract has the CAS number 85507-69-3.

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Aloe name derives from “alloeh” in Arabic and “halal” in Hebrew, which means bitter

shiny substance. Most of the aloe plants are non-toxic but some are extremely toxic,

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containing a hemlock-like substance.

The plant grows in a large variety of climates including temperate and subtropical areas

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although is native of southern and eastern Africa along Nile in the Susan and then it was
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introduced in North Africa and Mediterranean countries (Sahu et al., 2013; Manvitha &
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Bidya, 2014). The plant cannot survive freezing temperatures. Each plant has normally

12 to 16 leaves (between 25-30 cm long, while the 3-10 cm across the base) weighing
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up to 1.5 kg when mature and with saw-like teeth along their margins (Ahlawat &
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Khatkar, 2011). It flowers from October to January and the long inflorescence has a

large number of small bright yellow or red flowers. Propagation is generally vegetative.
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Fruits develop from February to April (Manvitha & Bidya, 2014) and contain many

seeds (Sahu et al., 2013). The leaves are covered by a thick cuticle and successive
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leaves have fewer whitish spots and grey-greenish in colour (Ahlawat & Khatkar,

2011).

Aloe vera is not a demanding plant in terms of water, therefore for areas that face the

problem of droughts, the cultivation of aloe may be a good option because it is

economically appealing to the farmers (Manvitha & Bidya, 2014). However cultivation

of aloe demands skills and it is very labour intensive. In fact, leaves can be harvest after
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7-8 months after planting using a sharp knife. The year with highest yield is the second

but good yield can be achieved during 4 to 5 years. The life span is about 12 years

(Eshun & He, 2004; Ahlawat & Khatkar, 2011).

Generally, 3 to 4 leaves are pulled away from the plant stalk and cut at the white base.

Care has to be taken regarding to prevent the damage to the outer rind of the leaves and

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to maintain the seal at the base of the leaf in order to prevent microbial contamination

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(Manvitha & Bidya, 2014).

The leaves of Aloe vera are constituted by the rind (or skin) which is a thick epidermis

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covered with cuticle surrounding the mesophyll. This can be differentiated into

chlorenchyma cells and thinner walled cells that form the parenchyma (Ramachandra &

Rao, 2008).
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Flowers can also be dried after collection (generally between December and January).
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Aloe leaves are dried in shade and then, in sun before storage at refrigerated

temperatures or processing. When dried, Aloe vera is a black powder but when frozen it
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is a gelatinous substance.
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The aloe leaves secrete two exudates, one is produced by the pericyclic cells under the

cutinized epidermis of the leaves and it is a reddish-yellow juice, also called latex. The
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other exudate is produced by the thin-walled tubular cells in the inner central zone

(parenchyma) of the leaf and it is a transparent, slippery mucilage or gel, called A. vera
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gel (Joseph & Raj, 2010). This gel is clear, tasteless and odorless (Pal et al., 2013).

The first exudate is used as laxative while the gel is used to treat skin burns. The gel is

not laxative because it contains no anthraquinones but total leaf extracts may contain

them (Vogler & Ernst, 1999)

Eshun and He (2004) have distinct three portions in the Aloe vera leaves as: i) yellow

sap, constituted mainly of anthraquinones (1,8-dihydroxyanthraquinone derivatives and

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their glycosides. Aloin is a constituent of the anthraquinone complex); ii) internal gel or

the fillet; iii) the rind, composed of rinds, thorns, tips and bases. Ramachandra & Rao

(2008) have made an interesting review on the processing methods of Aloe vera

including the stabilization of the gel and the effect of heat on gel components. Martínez-

Romero et al. (2013) conducted a study to evaluate the effect of ultraviolet light in the

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aloin content of Aloe vera. The results revealed that aloin content increased over time in

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gel, rind and latex.

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4. Uses in folk medicine

It has been widely used empirically for the treatments of many disorders such as burns

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and wounds of ancient civilizations. Other uses include seborrheic dermatitis, thermal
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burns and sunburn, cystic acne, peptic ulcers, amputation stump ulcers, lacerations,
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colds, tuberculosis, gonorrhoea, asthma, dysentery and headaches. It has been used as

laxative and insect repellent (Shelton, 1991).

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The benefits for health include: improvement of immune system; wound healing;
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protection against X-rays skin damage; protection against lung cancer; protection

against intestinal problems; increasing high density lipoprotein; reducing low density
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lipoprotein; reducing glycemia in diabetics; treating genital herpes and psoriases.

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5. Nutrients and bioactive compounds composition

Many factors can affect the nutrients composition of Aloe vera such the species and

edaphoclimatic conditions (Henry, 1979). However factors like the age of the plant can

also influence its composition. Many studies report the composition of aloe in different

compounds, but none of the individual chemicals gives the results of aloe, indicating a

synergetic effect (Henry, 1979; Lakshmi & Rajalakshmi, 2011). Tables 2 and 3 resume
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the nutrients composition of Aloe vera. Femenia et al. (1999) has made a complete

characterisation of the different parts of Aloe vera plant, including rind, filet and gel.

Later on, the same group of research studied the influence of heat and dehydration on

the bioactive polysaccharide acemannan and cell wall polymers of Aloe vera.

Acemamman (acetylated gluconmanan) is a polysaccharide rich in mannose units

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located within protoplast of the parenchymatous cells that improves wound healing,

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modulates immune function and antiviral effects (Chandegara & Varshney, 2013).

Glucomannan is another polysaccharide that can be found in Aloe vera. This is a good

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moisturizer and it is used in cosmetics (Chandegara & Varshney, 2013).

The activity of aloe polysaccharides depends on the degree of acetylation, molecular

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weight, type of sugar and glycosidic branching. The polysaccharides structure can
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change depending on the growing conditions of Aloe vera. Chun-Hiu and co-workers
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(2007) reported the antioxidant activities of polysaccharides from Aloe vera.

Due to the high water content, Aloe vera gel is low caloric. In fact, considering one
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serving of 200 mL it contributes with less of 5 kcal (Rodríguez et al., 2010).

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Nutritional variation is due to the process that was subjected to gel and growing

conditions, soil, climate and other geographical conditions (Ramachandra and Srinivasa,
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2008).

Carbohydrates are the main components of aloe gel, the main carbohydrates in Aloe
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vera are shown in Table 4. The variability is due to Aloe vera products often implicating

some type of processing. This processing may cause irreversible modifications to

carbohydrates, affecting their original structure, which may promote important changes

in the physiological and pharmacological properties of these components (Femenia et

al., 2003).

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6. Biological activities

Till now several therapeutic indications are attributed to aloe, as healing properties and

beneficial effects on skin inflammation. Several in vivo and in vitro experiments

evidenced the anti-inflammatory, anti-arthritic and antibacterial activity.

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Moreover other biological activities (or healthy effects) are attributed to aloe such as

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anti-obesity, antidiabetic, anti-inflammatory, immune modulator, antioxidant and

anticancer. Some of them are related to specific compounds of aloe. Phytosterols of aloe

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can bind to cholesterol causing a hypolipidemic effect and have also showed a

hypoglycemic effect in diabetic mice (Pothuraju et al., 2016); while its anthraquinones

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are degraded to metabolites (aloe-emodin-9- anthrone and aloe-emodin) in intestine that
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are responsible for its laxative properties; but other therapeutic effects are not still
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correlated well with a specific components (Radha & Laxmipriya, 2015). Regarding the

glycemic control and prediabetes and type II diabetes although there are several
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published works suggesting this effect, more complete trials are still needed to clearly
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determine the benefit of aloe (Suksomboon et al., 2016).

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Wound healing and cell proliferation

Aloe vera is known as a healing plant and has been used in several cultures for the
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treatment of skin injuries (Hashemi et al., 2015). Glycoproteins and lectins have been

found to have cell proliferation activities (Winters et al., 1981; Danof et al., 1983;

Reynolds & Dweck, 1999). The attempt to isolate glycoproteins and lectins from Aloe

vera gel fractions has permitted the finding of cell proliferation activity. Early in vitro

assays tested a 29 kDa glycoprotein and found to enhance the proliferation of kidney

cells in hamsters and human dermal fibroblast (Yagi et al., 1997). Furthermore, in vitro
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and in vivo studies of the effects of a 5.5 kDa glycoprotein found enhancement of

keratinocyte proliferation, confirmed by accelerated closure of a scratch made on a

monolayer of human keratinocytes. This glycoprotein stimulated the formation of

epidermal tissue. The glycoprotein is linked to saccharides, 70 % of which is mannose

(Choi et al., 2001). Studies by Tarameshloo et al. (2012) suggested that Aloe vera can

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infiltrate into skin tissue and act on the wound healing process as a whole, exhibited as

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an increase in activity of biological factors involved in the repair process.

Acemannan, the major sugar residue, has been extensively investigated and proven to

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stimulate wound healing and hard tissue regeneration by inducing cell proliferation and

stimulating Vascular Endothelial Growth Factor (VEGF) and type I collagen synthesis

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(Chantarawaratit et al., 2014). VEGF is important in new blood vessel formation and
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for inducing endothelial cell proliferation and migration (Rossiter et al., 2004). Recent
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studies have demonstrated the importance of the acetyl groups in acemannan and their

connection with cell proliferation, finding a relationship between acemannan acetyl

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groups and the expression of VEGF and type I collagen. Deacetylated acemannan
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showed reduction in the expression of VEGF and type I collagen expression in

fibroblasts (Chokoboribal et al., 2015). Acemannan also stimulated fibroblasts present

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in wound granulation tissue and secretion of collagen (Xing et al., 2015).

Further studies have searched for the mechanism of acemannan in wound healing,
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results indicating that acemannan may induce cell proliferation by promoting cyclin-

dependent cell cycle progress. Studies in skin fibroblasts not only showed enhanced

proliferation by acemannan but also a change in the cell cycle progress from C1 phase

to S phase. It is thought that acemannan promotes cell proliferation via translational

regulation of cyclin D1, one of the major factors involved to induce the transition of G1

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to S phase. Exposure to the polysaccharide showed increased cyclin D1 protein

expression in a dose dependent manner (Xing et al., 2015).

A recent review focused on the treatment of psoriasis concluded that the studies

analysed are contradictory and only the cutaneous administration could be considered

safe (Miroddi et al., 2015).

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Intestinal absorption and purgative action

Aloe is also used as a laxative due to its ability to reduce intestinal absorption of water.

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Active anthraquinones such as aloin, aloe-emodin and emodin are linked to the

purgative action of aloe. Aloin can be metabolized by the colonic flora to reactive aloe-

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emodin, this last compound is responsible for the purgative activity of aloe.
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Probiotics originating from Aloe leaf (POAL), specifically Lactobacillus brevis has
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been isolated from naturally fermented aloe gel and have demonstrated to inhibit the

growth of harmful enteropathogens without restraining the growth of normal

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commensals in the gut (Kang et al., 2014).

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Aloe-emodin and emodin have been injected directly into the caecum to monitor their

purgative activities. Results found that aloe-emodin, emodin and rhein synergistically
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exerted a potentiating purgative effect on mice (Yagi & Yamauchi., 1999). Studies by

Suboj et al. (2012) conducted on isolated aloe-emodin found to inhibit colon cancer cell
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migration by reducing DNA binding activity of nuclear factor K-light-chain-enhancer of

activated B cells.

Beneke et al. (2013) investigated the effect of gel and whole leaf extracts from three

species of aloe on the modulation of drug efflux across rat intestinal tissues. Results

demonstrated an increase in drug permeability in the presence of Aloe vera gel and

whole leaf materials. Aloe vera did not inhibit drug efflux across the excised rat
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intestinal tissue; this is thought to be attributed to opening of tight junctions by Aloe

vera gel and precipitated polysaccharides. An in vitro study showed Aloe vera able to

reduce the transepithelial electrical resistance of the Caco-2 monolayer, linked to the

ability to open tight junctions between adjacent cells. These results also demonstrated

an enhanced transport of insulin across the cell monolayers (Chen et al., 2009).

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Antiallergic activity

Studies by Ro et al. (2000) isolated a 10 kDa glycoprotein found to reduce the release of

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histamine and promoted the synthesis and secretion of leukotrienes in activated lung

mast cells of guinea pig. The glycoprotein decreased dose-dependently protein kinase C

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and phospholipase C activities, inhibiting mass diacylglycerol and phospholipase A
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activity, blocking Ca++ influx during mast cell activation.
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Antiinflamatory and immunomodulatory effect

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Aloe vera can inhibit the inflammatory process by reduction of leukocytes adhesion as
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found by Duansak et al. (2009). The administration of aloe has been demonstrated to

result in an increase in phagocytic and proliferative activity by inhibiting the

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cycloocygenase pathways and reducing prostaglandin E2 production, which play a role

in inflammation (Im et al., 2005; Park et al., 2009).

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Transcription levels of albumin and tumor necrosis factor α-genes are involved in the

early phase of acute inflammatory response. In rats treated with aloe-emodin, there was

an observed abolishment of the transcription of the albumin gene. Tumor necrosis

factor-α was weakly detectable in protected livers after aloe-emodin administration.

Histological analysis showed a reduced inflammatory infiltration on lymphocytes and

Kuffer cells observed in rats treated with aloe-emodin (Arosio et al., 2000).
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Hepatoprotective activity

Anthraquinones can act as antioxidants and are involved in free-radical-mediated

reactions during the inflammatory response. Reactive oxygen species and free radical

reactions are involved in inflammatory response and can contribute to liver necrosis.

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Arosio et al. (2000) carried out in vivo studies on rats with CCl4 intoxication and

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administrating aloe-emodin to observe the hepatoprotective activity of the antraquinone.

The morphofunctional and molecular changes normally induced by CCl4 were reduced

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by aloe-emodin. The antraquinone is likely to protect against hepatocyte death and the

inflammatory response subsequent to lipid peroxidation.

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Phytosterols found in aloe, specifically iophenol and cycloartanol, have the ability to
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induce the downregulation of fatty acid synthesis and upregulate fatty acid oxidation in
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the liver, resulting in reduction in intra-abdominal fat and hyperlipidemia improvement.

The studies by Misawa et al. (2012) found an improvement in metabolic syndrome-

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related disorders and liver steatosis in Aloe-sterol treated fatty rats. The results also
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found aloe to suppress obesity-induced inflammatory response by reduction of cytokine

levels.
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Aloe vera gel can also prevent ethanol-induced fatty liver by suppressing RNA

expression of lipogenic genes in the liver. Aloe gel also showed a potential decrease in
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cholesterol levels and the risk of cardiovascular diseases (Kumar et al., 2013).

Antibacterial, antifungal, antiviral and antiprotozoal activity

In vitro studies have shown that Aloe vera displayed antimicrobial activity on Gram-

negative and Gram-positive isolates. Polysaccharides have been attributed to direct

bacterial activity through phagocytic leucosytes stimulation to destroy bacteria.

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Acemannan preparations were found to activate NF-kappa B directed luciferase

expression (Pugh et al., 2001). The activation of the transcription factor NK-kappa B

controls the expression of multiple genes in activated monocytes/macrophages (May &

Ghosh, 1998).

The gram-negative bacterium Heliobacter pylori can cause the development of gastritis,

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peptic ulcer, gastric adenocarcinoma and MALT lymphoma. Studies by Wang et al.,

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(1998) on the effect of aloe-emodin on the N-acetyltransferase activity in Heliobacter

pylori showed dose-dependent inhibition of the bacterium, a 90 % inhibition was

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achieved when using concentrations of 925 µM aloe-emodin. Other in vitro studies

conducted by Cellini et al. (2014) tested multiresistant strains of H. pylori on A. vera

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gel, showing inhibition of the bacterium when using concentrations of aloe no greater
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than 100 mg. The same group of researchers attributed the inhibition of H. pylori to the
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polysaccharides present in the gel exhibiting an antiadhesive effect.

Other studies conducted on a 14 kDa isolated protein have reported the protein to
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exhibit potent antifungal activity against different Candida species, specifically

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Candida paraprilosis, Candida krusei and Candida albicans. Sequencing showed the

isolate to be a lectin like protein. However the absence of hemaglutinating activity

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confirmed it to be an antifungal protein. The inflammatory response can occur by the

lipoxygenase (LOX) pathway, responsible for leukotriene (LT) synthesis or by the

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cyclooxygenase (COX) pathway, resulting in the production of prostaglandins (PG).

The aloe protein showed LOX and COX inhibitory activity, suggesting the protein can

be used to reduce LT and PG synthesis. The protein was also found to inhibit trypsin

showing protease inhibitory function (Das et al., 2011).

Studies have also suggested Aloe vera to possess antiviral activity preventing virus

adsorption, attachment or entry into the host cell. A study by Zandi and Rastian (2007)
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has shown Aloe vera gel to have antiviral activity against herpes simplex virus (HSV)

type 2 strains. The study was conducted on Vero cells with different concentrations of

aloe crude extract on the post attachment stages of the virus replication cycle. At a high

concentration the extract was shown to inhibit the performing of cytopathic effect due to

the HSV-2 replication in Vero cells. In addition, the anthraquinones present in aloe have

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been reported to exhibit antiviral activity and inhibitory mechanism against influenza A

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virus replication and virus induced cytopathic effect (Li et al., 2014).

Other studies have shown aloe to increase CD4 count, resulting in an improvement of

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the immune system, possible helping HIV infected individuals. It is thought that the

CD4 count increase can be attributed to the in vitro inhibition of HIV by acemannan or

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the immune-modulatory effects of aloe components (Olantuya et al., 2012). The results
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obtained form part of a preliminary study; there are still many hypothesis to be tested
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that can explain the Aloe vera activity against HIV.

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Anticancer activity
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Aloin has been proposed as a potential therapeutic option in cancer. Aloin treatment has

shown significant in vitro inhibition of VEGF-induced angiogenic response of human

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endothelial cells. Aloin has been found to inhibit tumor angiogenesis and growth by

signal transducer and activator of transcription 3 (STAT3) activation (Pan et al., 2013).
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Aloe-emodin, has been found to possess antiproliferation effects on some types of

cancer cells, inhibiting N-acetyl transferase activity and gene expression. This activity

plays a crucial role in the aryl amine carcinogens metabolism, found in human

malignant melanoma cells (Lin et al., 2005).

7. Effects of processing Aloe vera

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The use of Aloe vera products implicates some types of processing. Processing of Aloe

vera gel has become a big industry worldwide due to its multiple applications

(Ramachandra and Srinivasa, 2008). Aloe vera has innovated the food industry by being

introduced as a functional food for the preparation of conventional products as

beverages, milk or ice cream in addition to its use as an edible coating for fruits

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(Rodríguez-González et al., 2011; Benítez et al., 2015).

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Processing may cause irreversible changes to the original structure of the

polysaccharides and other compounds. The study of Femenia et al. (2003) investigated

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the effects of heat treatment and dehydration on bioactive compounds, the results show

the modification of acemannan. It was particularly significant when dehydration was

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above 60 °C. The importance of the physico-chemical changes detected in Aloe vera
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dehydrated parenchyma depended on the temperature used during the drying process.
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The bioactive polysaccharide acemannan underwent similar losses of mannosyl residues

when dehydration was performed between 30 and 60 °C, above the latter temperature
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losses increased significantly. Further, the structural modifications detected on the

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acemannan polymers could be responsible for the important changes observed in the

functional properties of dehydrated filets. Deacetylation and reduction of galactosyl

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residues might have influenced the interaction between mannose chains affecting their

binding capacity.
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Chang et al. (2006) evaluated the effect of heating on barbaloin and polysaccharides

from Aloe vera juice. The maximum stability the polysaccharides was reached at 70 °C

and increasing this temperature led to a decrease in barbaloin content.

Time, temperature and sanitation are necessary to preserve biological activities of aloe

and physical stability of the finished products. After harvest of Aloe vera leaf, the

mixture of acetylated glucomannans produce a viscous psedoplastic gel, but this

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consistency is lost shortly after extraction, showing that the biological activities related

to these compounds could be related with the viscoelastic behavior of gel.

In the study conducted by Rodríguez- González et al. (2011) physico-chemical

modifications promoted by pasteurization treatments were reported. Pasteurization

seemed to increase the yields in acemannan content, however this effect was probably

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due to the decrease in ethanol-soluble mannose for all treatments.

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Miranda et al. (2009) evaluated the influence of temperature on antioxidant capacity

and physical-chemical properties. The drying temperature exerted a clear influence on

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most of the quality parameters. A drying temperature of 80 and 90 °C resulted in

significant variation in add or loss of the physicochemical and nutritional properties of

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the gel. In fact at these temperatures an increased nutrient loss was observed. However,
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the content of crude fibre, Ca, and vitamin C were decreased in the rehydrated samples
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compared to fresh A. vera gel. .In addition, the antioxidant capacity of the gel was

decreased at these temperatures.

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8. Current applications and future trends

From the plant, different preparations are usually obtained, as Aloe vera gel (clear
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mucilaginous aqueous extract of the inner leaf pulp) and Aloe vera latex (located in the

vascular bundles, pericyclic tubules, in the outer leaf pulp adjacent to the thick rind),
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and they can be used as topical or oral therapeutic agents (Boudreau & Beland, 2006).

Aloe latex can be found as OTC laxative drug due to the presence of anthraquinones,

that include a laxative constituent called aloin (http://www.iasc.org/). In the case of

products for oral consumption aloin is less than 100 ppm while for topic use the limit,

accepted industry limit is 50 ppm.

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Leaves of Aloe vera can be used to prepare juice and then it can be converted in powder

or concentrated (http://www.iasc.org/).

It is a common thread in all works the lack of information about the exact part of the

plant used and the specie or species involved (Boudreau & Beland, 2006);

In an extensive review conducted on the safety of several aloe species, the concern

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about the anthraquinones that are present in the aloe derivatives come into view. But

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this study demonstrated that in several works carried out with aloe barbadensis extracts

that no phototoxicity was observed; based on this and in other data evaluated it is

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concluded that the aloe barbadensis extracts mentioned are safe as cosmetic ingredient

whereas for other species the data available are insufficient to allow the same

conclusion (Andersen, 2007).

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More research is required to achieve high quality products that meet the expectations of
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the consumers, as well as enhance the investment of farmers, although significant

progresses have been done on pre- and postharvest treatments to improve food quality.
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Some of these treatments include the use of edible coating with aloe gel incorporated to
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improve the shelf life of fruits.

Aloe vera was used to improve the quality of lowmeat beef burgers. Results indicated
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that the addition of Aloe vera contributed to some extent to decreased cooking loss and

diameter reduction in the burgers. Moreover, increased concentrations of Aloe vera led
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to improvements in the water absorption and texture of the burgers as well as their lipid

stability. It was found that Aloe vera acts as a hydrocolloid and improves the quality of

burgers (Soltanizadeh & Ghiasi-Esfahani, 2015).

Khoshgozaran-Abras et al. (2012) have successfully incorporated Aloe vera gel into

chitosan.

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Aloe vera gel was used as preharvest treatment to maintain postharvest table grape

quality (Castillo et al., 2010).

Aloe vera has also been used to improve the postharvest fruit quality of sweet cherry

(SP Patent Filed P200302937, Martínez-Romero et al., 2006), table grapes (SP Patent

P200302937, Valverde et al., 2005, Serrano et al., 2006;); apple slices (Chauhan et al.,

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2011), kiwifruit slices (Benítez et al., 2015) and blueberries (Vieira et al., 2016).

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According to the results of Benítez et al. (2015), Aloe vera was the best coating to both

extend the postharvest shelf life and maintain the sensory properties of the product

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along the storage period.

Conclusions
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Biological effects of Aloe have been extensively reviewed in the last two decades.
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During this period the scientific knowledge of this plant has exponentially increased at

the same time its therapeutic claims and the popular interest. In the past it was clear that
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aloe leaf gel has the ability for healing skin lesions although more studies were
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requested, but at present the mechanisms of action responsible for the different

biological effects of aloe are still far away of being completely clear.
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Very interesting applications of Aloe vera are being developed, such as its use as an

edible coating of fruits, which represents an effective and safe alternative to postharvest
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chemical treatments. However, in what regards to aloe applications, it is predictable that

new frontiers will open in near future, namely in the pharmaceutical industry due to the

knowledge of the exact mechanisms of action, effective doses and side effects of newer

pharmaceutical formulations based in aloe.

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Winters, WD, Benavides, R, & Clouse, WJ. (1981). Effects of aloe extracts on human

normal and tumor cells in vitro. Economic Botany, 35, 89-95.

Xing, W., Guo, W., Zou C.H., Fu, T.T., Li, X.Y., Zhu, M., Qui, J.H., Song, J., Dong,

C.H., Li, Z., Xiao, Y., Yuan, P.S., Huang, H., & Xu, X. (2015). Acemannan

accelerates cell proliferation and skin wound healing through AKT/mTOR

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signaling pathway. Journal of Dermatological Science, 79, 101-109.

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Yagi, A., Egusa, T., Arase, M, Tanabe, M., & Tsuji, H. (1997). Isolation and

characterization of the glycoprotein fraction with a proliferation promoting

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activity on human and hamster cells in vitro from Aloe vera gel. Planta Medica,

63, 18-21.

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Yagi, T, & Yamauchi, K. (1999). Synergistic Effect of Anthraquinones on the Purgative
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Activity of Rhein Anthrone in Mice. Journal of Pharmacy and Pharmacology, 51,
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93-95.
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Zandi, K., & Rastian, Z. (2007). Antiviral activity of Aloe vera against herpes simplex

virus type 2: An in vitro study. African Journal of Biotechnology, 6, 1770-1773.

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Table 1: Taxonomic classification of Aloe vera.

Rank Scientific Name and Common Name

Kingdom Plantae
Subkingdom Tracheobionta
Superdivision Spermatophyta
Division Magnoliophyta
Class Liliopsida

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Subclass Liliidae
Order Liliales
Family Aloaceae

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Genus Aloe L.
Species Aloe barbadensis Mill.or Aloe vera (L.) Burm. F.

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Table 2: Chemical composition of Aloe vera.

Nutrients Part of the plant Reference

Rind Fillet Gel
Water 90% 98% 99% Femenia et al., 1999

98% Bozzi et al., 2007

98.7-98.9% Rodríguez-González et al., 2011

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Total Lipids 2.7.%* 4.21%* 5.13%* Femenia et al., 1999

4%* Luta & McAnalley, 2005

Fatty acids

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C12:0 0.32 ppm* Nejatzadeh-Barandozi, 2013

C14:0 0.74 ppm*

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C16.1 1.32 ppm*
C18:2 n-6 102 ppm*
Sterols

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Sitoesterol 2.89% Bawankar et al., 2013

Stigmaesterol 2.1%
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Protein 6.33%* 7.26%* 8.92%* Femenia et al., 1999

Soluble sugars 11.2%* 16.5%* 26.8%* Femenia et al., 1999

17%%* Luta & McAnalley, 2005

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Polysaccharides 55%* Luta & McAnalley, 2005

633.7 µg/mg AIR Femenia et al., 2003

Dietary fibre 62.3%* 57.6%* 35.5%* Femenia et al., 1999

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Ash 13.5%* 15.4%* 23.6%* Femenia et al., 1999

Vitamins C (127.6/100g), E (0.25 Miranda et al., 2009

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mg/100g)
A, C, E, B1, niacin, B2, Ahlawat & Khatkar, 2011
choline, folic acid, B12
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* dry matter; AIR: Alcohol insoluble residues.

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Table 3. Mineral composition of Aloe vera.

Part of the plant

Compounds Reference
Whole/not mentioned Rind Fillet Gel
16%* Luta &McAnalley, 2005
Ca
460 ppm Henry, 1979
4.48%* 5.34%* 3.58%* Femenia et al., 1999

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3.58 g/100g Femenia et al., 1999
0.142 mg/ 2g ash Rajasekaran et al., 2005
Mg 93 ppm Henry, 1979

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1.22 ppm Femenia et al., 1999
0.157 mg/ 2g ash Rajasekaran et al., 2005

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0.90%* 0.76%* 1.22%* Femenia et al., 2000
Na 51 ppm Henry, 1979
3.66 g/100g Femenia et al., 1999

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0.162 mg/ 2g ash Rajasekaran et al., 2005
1.82%* 1.98%* 3.66%* Femenia et al., 2000
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K 85 ppm Henry, 1979
4.06 g/100g Femenia et al., 1999
1.84%* 3.06%* 4.06%* Femenia et al., 2000
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0.397 mg/ 2g ash Rajasekaran et al., 2005

P 0.02 g/100g Femenia et al., 1999
0.01%* 0.01%* 0.02%* Femenia et al., 2000
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Fe 3.9 ppm Henry, 1979

0.1 g/100g Femenia et al., 1999
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0.04%* 0.04%* 0.10%* Femenia et al., 2000

3.5 mg/ 2g ash Rajasekaran et al., 2005
Cu 0.47 ppm Henry, 1979
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0.06 g/100g Femenia et al., 1999

0.02%* 0.04%* 0.06%* Femenia et al., 2000
0.150 mg/ 2g ash Rajasekaran et al., 2005
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Zn 0.02 mg/100g Femenia et al., 1999

0.02%* 0.02%* 0.02%* Femenia et al., 2000
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0.378 mg/ 2g ash Rajasekaran et al., 2005

Al 22 ppm Henry, 1979
Zn 1 ppm Henry, 1979
Mn 0.59 ppm Henry, 1979
DMB- dry matter basis
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Table 4. Carbohydrate composition from Aloe vera.

Part of the plant

Compounds Liquid gel Gel fresh Gel juice Freeze dried Reference
(% total (mg/g DMB) (mol %) (mg sugar/mg DMB
sugars of aloe filets)
detected)

Mannose 62.9 - - - Ni et al., 2004

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- 92–106 - - Rodríguez-González et al., 2011

- - - 220.74 Femenia et al., 2003

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- - 15.1 - Nejatzadeh-Barandozi and
Enferadi, 2012

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Rhamnose - - - 0.33 Femenia et al., 2003

Arabinose - - - 0.62 Femenia et al., 2003

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Glucose 13.1 - - - Ni et al., 2004
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- - - 28.06 Femenia et al., 2003

- - 80 - Nejatzadeh-Barandozi and
Enferadi, 2012
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Galactose 1.5 - - - Ni et al., 2004

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- - - 12.02 Femenia et al., 2003

Acemannan - 113 – 139 - - Rodríguez-González et al., 2011

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Xilose - - - 1.57 Femenia et al., 2003

DMB- dry matter basis

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Highlights

- Botanical description, distribution and cultivation of Aloe vera are reviewed.

- Nutritional and bioactive compounds composition of Aloe vera is overviewed.

- Effects Aloe vera processing are addressed.

- Biological activities of Aloe vera are explored in detail.

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