African Natural Plant Products - American Chemical Society

Chapter 9

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Biology and Chemistry of the Genus Aloe from Africa Adolfina R. Koroch, H. Rodolfo Juliani, James E. Simon New Use Agriculture and Natural Plant Products Program, School of Biological and Natural Resources, and the New Jersey Agricultural Experiment Station (NJAES), Rutgers, The State University of New Jersey, 59 Dudley Road, New Brunswick, NJ 08901-8520

Aloe is a medicinal plant that has been used since ancient times by cultures in many countries and continents for many of the same applications. Africa is blessed with a wide variety of Aloe spp. each used by the indigenous cultures. Fleshy leaves are the source of two of the main products, gel and latex, with both products showing distinct differences in their chemical composition. Chemical composition of gel consists mainly of water with carbohydrate polymers and a range of other organic and inorganic components. In contrast, the chemical composition of the latex includes many phenolic compounds such as anthraquinones and chromones. The objective of this paper is to review the the botany, chemistry and pharmacological properties of Aloes from Africa.

Introduction, Botany and Ecology Aloe’s has been used in folk medicine for over 2000 years, and remains today, an important component in the traditional medicine of many cultures (1, 2). In the past decades, the popular use and interest of aloe gel products for the food, cosmetic and pharmaceutical industries has dramatically increased (2, 3). Aloes belong to the Aloaceae family and comprise a large genus of over 300 sp (4, 5). The genus is native to Africa from the southern Cape in South Africa to about 15°N north to the southern parts of the Arabian Peninsula (4).

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In African Natural Plant Products: New Discoveries and Challenges in Chemistry and Quality; Juliani, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2010.


172 Aloes vary in size from 30 mm to over 15 m high and they are more or less succulent (Figure 1) (6, 7). Aloe species are found naturally growing primarily in mainland Africa, with the majority of species in southern Africa and on the eastern side of the African continent. The largest numbers of Aloe species are found along the moister central north-south mountain ranges of mainland Africa, and in the arid south and south-west of the Madagascar island. Some species are very widespread in distribution, such as A. buettneri (6), while others have a very restricted distribution. Newton (8) prepared a geographical distribution list of Aloe species including the total number of species and endemic species in different countries of Africa. Madagascar and the isolated Indian Ocean Islands are the ones with highest rate of endemism (100%). Aloes can grow in a wide range of habitats from forests to exposed rock surfaces, however, they are absent in moist lowland forest of mainland of Africa. The genus occupies a considerable altitudinal range from sea level up to about 3,500 meters above sea level. For example, A. dichotoma has been proposed as a candidate for studying climate change in the arid Desert and Nama Karoo biome in Namibia (9). In the wild, Aloes occur on a wide range of soil types and substrates. They can grow on dolomite, granite, gypsum and limestone (8). Garcia-Hernandez et al. (10) identified significant nutrient interactions of the Aloe crop growing in an irrigated calcareous desert soil. The phenotypic diversity within and between Aloe spp. is significant. Some Aloe plants have short stems that are completely hidden by the leaves. They are succulent plants with perennial, strong and fibrous roots and numerous leaves, carrying spines in their margin. The leaves can be arranged in rosettes and some species have underground bulb. Yet, other species have long stems being arborescent, shrubby, sprawling, climbing or pendulous. Arborescent species can reach 15 meters height and may be branched or unbranched. Flowers are produced on racemose inflorescences. Usually the racemes are erect, but in some cases they are oblique or more or less horizontal. In most cases the flowers are brightly colored and very conspicuous (6-8). Aloe juice has been used since ancient times in the treatment of several diseases as well as for cosmetic use by different cultures over history (11). It is likely that these diverse uses have been at least partially responsible for the spread of some of the Aloe onto different continents. Today, Aloe vera is considered to be the most popular and most widely internationally traded and the one most extensively researched (3). As observed with many other species including medicinal plants, the destructive harvest of some of the Aloe, its over-collection and the inadvertent destruction of plants from harvesting the leaf exudates as well as the loss of the plants habitat has led in some regions to the Aloe being threatened. Some Aloe species have been reported as endangered species (8). In vitro culture is a powerful tool that offers the possibility to produce thousands of genetically identical plants within a short time frame, thus providing one avenue of presering germplasm (12). A few Aloe species have been successfully propagated through tissue culture techniques. For instance, a rapid micropropagation protocol of endangered medicinal Aloe vera L var. chinensis (13) and A. polyphylla (14) have been reported. Also, in vitro regeneration of A.


173 arborescens via somatic embryogenesis from young inflorescences as source of starting material has been achieved (15).


Chemistry The chemistry of aloe has been studied for many years (2, 4, 16, 17). Aloe vera is extensively recognized for containing a number of unique organic phytochemicals that showed medicinal properties. Although there is a large number of Aloe species, only few of them are of economic importance (16, 18). Though this paper focuses on the Aloes of Africa, we will be reported selected findings of Aloe vera, as the information is more extensive and lessons can be gleaned from the biological understanding of that species. Most of the research has been focused on the commercial aloes including A. vera and A. ferox, the southern African aloe. Leaves of A. vera plants produce two major medicinal products: (i) a yellow latex, or exudate, mainly consisting of bioactive phenolic compounds such as anthraquinones and chromone (19-21) and (ii) a mucilaginous jelly from the parenchyma cells of the plants. The last one is known as “Aloe vera gel” (3, 17). The gel is mainly composed of water and mucilage containing a high content of polysaccharides. Enzymes such as oxidase, a catalase, and amylase have also been reported (3, 17, 22). Many of the beneficial effects of this plant have been attributed to the presence of polysaccharides. Acetylated mannan is the primary polysaccharide in the pulp (2, 22). The predominant monosaccharides in the pulp are manose and glucose, xylose, rahamnose, galactose, arabinose fructose and uronic acid (22). Besides leaves, roots are also a storage site for the accumulation of many interesting secondary metabolites such as anthraquinones, pre-anthraquinones, anthrones, chromones, alkaloids, flavonoids, coumarins. One of the main groups of phenolic constituents are anthraquinones, and these have been reported in roots of aloe (16, 24, 25), in leaf exudates of A. elgonica (26) and A. ferox (27). However, in one study, anthraquinone glycosides were not been detected in the root (16). Other group of phenolic constituents are the chromones. Using HPLC analysis, aloesin, aloin and aloeresin A have been identified in many Aloe species (4, 16, 24, 28, 29) (Figure 2). 7-O-methylaloeresin A has been reported in A. marlothii and A. ruperstris in leaf exudates (30). In addition, a number of chromones with different structures present in the gel of A. vera have been identified and reported (19, 20, 31). Also, 5-methylchromone derivates have been described from A. broomii, A. africana, and A. speciosa (32) (Figure 1). Aloeresin H (8-C-β-D-glucopyranosyl-7-hydroxy-5methylchromone) has been elucidated by degradation experiments combined with 1D and 2D NMR data from A.ferox (33) (Figure 1).



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Figure 1. A. ferox (left) and A. speciosa (right) from South Africa. OH

OH OH

HO O

OH

HO O H

OH O

HO

H

OH OH

O OH Aloin A

O

Aloesin OH

O

OH

HO O H

H

O

OMe O

OH

OH

Me

O

OH

O

OH

OH O

OH

OH Aloin B

OH

Aloenin

OH OH

Figure 2. Chemical structures of some components isolated from Aloe species.



175 Recently, Duri et al. (34) isolated from Kenyan commercial aloes two new compounds, 10-O-β-D-glucopyranosyl aloenin and 8-C−β-D-glucopyranosyl-7O-methyl-(R)-aloesol together with aloenin (phenylpyrone derivative), aloenin 29-p-coumaroyl ester, aloenin aglycone, orcinol and acetylorcinol. Anthrones are also an important group of components present in Aloe species, Aloin A and B collectively known as barbaloin are the most important bioactive phenolic component (16, 35, 36). Also, a number of oxanthrones have been reported occurring in different Aloe sp. 10-hydroxylaloin B 6’-O-acetate was isolated from A. claviflora (37), C-O-diglucosylated oxanthrone (also known as littoralside) from leaf exudates of A. littoralis (38), and 5 Hydroxyaloin was isolated from A. microstigma (39). Aloenin was isolated from A. arborescens and later reported in other Aloe sp (36, 40, 41). Dagne et al. (42) revealed the presence of 10-hydroxyaloin B and deacetyllittoraloin from leaf exudates of A. littoralis. Several methods are currently used to identify the secondary metabolites of aloe, such as Thin Layer Chromatography (TLC) (30, 43), High Performance Liquid Chromatography (HPLC) (44), High Performance Liquid Chromatography in combination with nuclear magnetic resonance spectroscopy (HPLC-NMR) (45), High-Speed Countercurrent Chromatography (HSCCC) combined with traditional pretreatment (46), Gas Chromatography/ Mass Spectrometry (CG/MS) (47, 48). Later, Karagianis et al, (45) showed the potential of using HPLC-NMR (High Performance Liquid Chromatography in combination with nuclear magnetic resonance spectroscopy,) in the structure elucidation of aloe metabolites without prior isolation. Flavonoids are widely distributed in many groups of plants. Viljoen et al., (49) showed that flavonoids occur as major compounds in 31 Aloe spp. out of the 380 studied. Four major flavonoids were detected in aloe: naringenin (flavanone), dihydroisorhamnetin (dihydroflavonol) and aspienin and isovitexin (flavones). Moreover, the distribution of the different flavonoids provides valuable chemotaxonomic evidence (49). Although aloe plants are known as medicinal plants, there are actually a few studies showing aloes to be poisonous (50). A few local species such as A.gillilandii, A. ballyi, A. ruspoliana, A. ibitiensis and A. deltoideodonta, among others, has been reported to contain toxic hemlock alkaloids especially γconiceine (51, 52). These compounds may be easily recognized because of their mousy smell. Further phytochemical investigations confirmed the presence of hemlock alkaloids in A. sabaea and also the presence of a new chlorinated amide, N-4’-chlorobutylbutyramide (53). In view of the potential implications of the presence of alkaloids, screening for alkaloids before recommending an aloe species as medicinal has been suggested (16). Although A. vera and A. ferox species are the most important commercial in the international markets, it is largely the presence of anthrones and polysaccharides content that determine the plants effectiveness for therapeutic activity. There are other Aloe species that could be promoted for similar purposes when those species contain one or both groups of bioactive compounds. The biological activities of the Aloe sp could be attributed to synergic actions of the components rather than from a single component (16).


176 Moreover, Aloe spp. endemic from Madagascar such as A. suzannae, A. helenae and A. vaotsanda contain unique flavonoids (16, 49).

Biological Activity Aloe plants have always been used for its medicinal and therapeutic properties (54), although there was not any clear understanding of the basis of such properties.


Antioxidant Activity Oxidation represents a crucial part of aerobic life and our metabolism. It consists in the transfer of electrons from one atom to another. Sometimes, the electron flow becomes uncoupled, generating thus free radicals. These molecules are unstable and very reactive with all biological molecules, producing in some cases irreversible damages or destruction in a variety of tissues. Oxidative damage plays an important role in many degenerative processes and diseases. Therefore, there is a strong interest in the search of natural antioxidant products from plants with low cytotoxicity. There are many mechanisms of antioxidant activity including scavenging free radicals, inhibiting the enzymes that produce free radical, or protecting the antioxidant defenses (55). Several authors have investigated the antioxidant components in A.vera products of the exudate. Yagi et al., (56) reported the DPPH radical and superoxide anion scavenging activity in seven aloesin derivatives. Later, Beppu et al., (57) reported the oxygen scavenging activity of the two phenolic compounds (2’-O-p-coumaroylaloesin and 2’-O-feruloylaloesin), preventing thus the destruction of the pancreatic islets. The antioxidant activity of aloeemodin depends also on scavenging hydroxyl radicals (58, 59). Moreover, it appears that the antioxidant or pro-oxidant activity of aloe-emodin is related to its concentration (60). In vitro studies have demonstrated that A. vera latex derived anthraquinones in presence to ultraviolet light A (UVA) exhibited significant photo-oxidative damage to both cellular RNA and DNA (61). Several studies on photostability and phototoxicity of A vera extracts indicate that in presence of UV light it can generate the formation of free radicals (62, 63). Polysaccharides that are mainly found in the gel are also a group of compounds that exhibit antioxidant activities. It was demonstrated that APS-1 (mainly composed b mannose glucose in ratio 18:5) was effective in scavenging superoxide anion radical (dose-dependant fashion), hydroxyl radical, suppressed conjugated diene formation from LDL oxidation induced by Cu+2, and exhibited a protective effect on hydrogen peroxide-induced injury in PC12 cells (64). Also Kardosova et al. (65) showed that in vitro experiments with acidic and neutral polysaccharides were able to prevent lipid peroxidation by scavenging hydroxyl radicals.


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Finally, it has been reported that the growth stage of the aloe plants play an important role in the composition of the active constituents and thus in the antioxidant activity (66). Strong antioxidant activity was observed from the components of the inner gel. For example, Wu et al. (64) were able to isolate the main polysaccharide of leaf (APS-1) which is basically composed by mannose and glucose (18:5). APS-1 exhibit significant free radical scavenging and antioxidant activity, and protective effects on hydrogen peroxide-induced injury in PC12 cells. Traditional uses of Malagasy Aloe sp (A. vahombe and A. divaricata) include as purgative (decoction of leaves, very bitter), the leaf juice is used to consolidate limb fractures and the plant is also known for its ocytoxic properties (67). Anti-inflammatory Activity Inflammation is a normal and complex reaction by the body to an injury. Aloe has been used in traditional medicine for its anti-inflammatory use. The aqueous and chloroform extracts of aloe inhibit the effect on carrageen induced edema. This effect was associated with an inhibitory action on the arachidonic acid pathway via cyclooxygenase (68). Aloe gel components were able to suppress bacterial induced pro-inflammatory production of cytokines (systematically elevated after a bacterial invasion), namely TNF-α and IL-β (69). Aloe vera was evaluated as topical anti-inflammatory agent, and cinnamoylC-glucosylchromone (isolated from the exudates) was able to reduce croton oilear inflammation at an activity level comparable to hydrocortisone (70). Speranza et al. (71) demonstrated that 5-methylchromone (aloesin I) from dried exudates from A. ferox was able to reduce the oedema response induced by croton oil in the mouse ear. Moreover, Yagi et al. (56) pointed out the activity of p-coumaroyl and feruloyl groups on the inhibition of the cyclooxygenase 2 and thrombosane A2 synthase by aloin derivates. Species with higher concentrations of flavonoids (e.g. A. pratensis, A. humilis and A. pretoriensis ) showed high anti-inflammatory activity with values similar to those plants that accumulate anthrones and chromones (A. wickensii) (72). Anti-diabetic Activity Diabetes mellitus is one of the world’s major diseases, and since ancient times many cultures have been using medicinal plants to control diabetes (73). Several reports have pointed out the beneficial effects of A. vera in controlling blood glucose. As such, A. vera has been cited as one of the seven most promising herbs or supplements to control blood glucose in blood (74). Aloe gel, rich in glucomannan has been reported to have hypoglycemic effects; however the mechanisms have not been elucidated (75). In addition, Aknimoludam et al. (76) postulated that aloe preparations not only reduce the plasma glucose levels, but also can be used as a prophylactic agent to prevent


178 the hyperglycemia. Okyar et al. (77) observed hyperglycemic activity in A. vera leaf extract and suggested the potential use on the treatment on non-insulin dependant diabetes mellitus.


Anti-cancer Activity Aloe-emodin (hydroxyanthraquinone) has been reported with a unique in vitro and in vivo antineural tumor activity with selective toxicity (78). Aloeemodin not only can behave as an anti-tumor agent, but also as anti-angiogenic compound. Angiogenesis is a complex process, and it is required both for cancer progression and metastasis. Under certain pro-angiogenic signal cells are activated and are involved formation and differentiation of blood vessels. It was also suggested, that it could be a candidate drug for photodynamic therapy (79). Other compounds, such as di (2-ethylhexylphthatate) have shown antileukaemic and antimutagenic effect and were extensively investigated by Lee and collaborators (43, 80). The effect of aloe polysaccharides on chemopreventive agent was examined on inhibition of formation of B[a]P-adducts DNA in vitro and in vivo (81, 82). Also, a mannose rich polysaccharide, PAC-I isolated from aloe has shown to have potent stimulatory activity on murine peritoneal macrophage. When PAC-I was administrated in vivo is capable of prolonging the survival of tumor bearing mice (83). Wound Healing Activity Of all the uses of aloe, one of the most popular is for the treatment of wounds and burns (2, 3). However, the complete composition of aloe components and the component responsible of wound healing is still being unraveled. Restoration of the tissue integrity is one of the fundamental processes during wound healing. The early stages of wound healing are characterized by laying down provisional matrix, follow by the formation of granulation tissue and synthesis of collagen and elastin. Collagen is the major protein of extracellular matrix and it is the predominant constituent of the final scar. Wounds treated with A. Vera not only increased the provisional matrix (84) but also the collagen content (85). Choi et al. (86) were able to isolate a glycoprotein fraction (5.5 kDa) that is involved in the wound healing effect of A. vera via cell proliferation and migration. This glycoprotein fraction was able to accelerate the wound healing on a monolayer of human keratinocytes and also to enhance wound healing in hairless mice with significant cell proliferation. There is cumulative evidence supporting the effectiveness of A. vera products in burn healings, radiation skin reactions, but further well designed trials with sufficient details of contents should be carry out (87, 88). In the wound healing process, infection also plays an important role. Aloe gel also exhibits antimicrobial, antifungal and anti-viral properties (89). The inner gel of aloe exhibited antimicrobial activity against Shigella flexneri and


179 Streptococcus pyogenes (90). The activity of three compounds (aloe-emodin, chrysophanol and aloin A) isolated from A. ferox have been shown to be effective against both Gram negative and Gram positive bacteria, demonstrating a broad spectrum potential of the plant as antimicrobial agent (91). Other Activities


Aloe-emodin and Aloin A has been studied as hypotensive agents. Aloeemodin aloe-emodin has emerged as a potent blood pressure reducing agent and caused 79% decline in blood pressure at a dose of 3 mg/kg in rats (92).

Conclusions The genus Aloe from Africa is highly diverse with hundreds of species, however, only a minor number of these diversity has been explored in search for new bioactive components. Many of them are being use extensively by traditional healers, suggesting that the genus can be the source of potential new compounds that are waiting to be discovered or commercialized. A. vera and A. ferox are two popular and well species that contain many unique constituents with biological activity and with application to the pharmaceutical, cosmetic, personal care products sectors as well as to the continued uses in traditional medicines.

Acknowledgements This work was conducted as part of our Partnership for Food and Industry in Natural Products (PFID/NP) project with funds from the Office of Economic Growth, Agriculture and Trade (EGAT/AG) of the USAID (Leader Contract Award No. AEG-A-00-04-00012-00) and with support from the USAID-Regional Center for Southern Africa. We thank Robert Hedlund, Larry Paulson, Carol Wilson and Jerry Brown, USAID Cognizant Technical Officers for each of the PFID/NP for their active involvement, support and encouragement. As our African research is implemented by and in concert with the ASNAPP network (www.asnapp.org) we thank the ASNAPP organization as well as the New Jersey Agricultural Experiment Station, Rutgers University who each provided support for this work. Lastly, we give particular thanks and recognition to those African small farmers, scientists, researchers and traders and healers who have always opened their doors to us.


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