Aloes and the immune system

2015

There is a moderate scientific literature on the immunological effects of extracts from plants of the genus Aloe. Unfortunately, it is difficult to assess the significance of many of these studies because of two problems. First, most studies have been undertaken using many different, poorly characterized, complex aloe extracts. Second, studies have been performed using several different Aloe species, making comparisons impossible. Although anecdotal reports describe a wide variety of both immunostimulating and immunosuppressive effects, controlled scientific studies have substantiated very few of these. Most studies that have been performed have focused on the clear mesophyll gel of the Aloe vera leaf and on its major storage carbohydrate, acetylated mannan (acemannan). Recently a unique pectin has been isolated from aloe mesophyll cell walls and appears to have unique and important properties. Some consistent properties have, however, been noted. Thus aloe gel extracts and partially purified acemannan preparations have mild anti-inflammatory activity and multiple possible pathways for this activity have been investigated. Aloe extracts also have some limited macrophage activating properties. These include the release of nitric oxide and the secretion of multiple cytokines. This macrophage activation may account for the effects of aloe extracts on wound healing, bone marrow stimulation, and their limited anti-cancer effects. Studies have also provided evidence to suggest that aloe extracts can influence apoptosis and lymphocyte function. The Madagascar species, Aloe vahombe(sic), has been claimed to possess a very wide array of beneficial activities, but this has not been independently confirmed.

Two features of the Aloe family make them somewhat unique in the field of medicinal plants. First, there is no agreement on which ailments they might cure and second, there is no agreement on the components within the aloe plant that may exert beneficial medicinal activity. Anecdotal reports describe a bewildering array of both immunostimulating and immunosuppressive effects. Few controlled studies have supported these claims and to this day, much uncertainty exists as to whether aloe extracts actually have significant beneficial activity. The controlled studies that have been undertaken have tended, unfortunately, to use complex mixtures or partially purified components which makes comparative analysis difficult. Nevertheless, they have tended to support a very limited range of effects on the cells of the immune system. Indeed, the recognized effects of aloe extracts appear primarily to affect innate immune mechanisms such as inflammation, rather than acquired immunity. They also tend to be quantitatively minor in nature. Nevertheless, taken as a whole, they may well account for the ‘good press’ that aloes have received over the years and for the continuing interest in the use of aloe extracts as immunomodulating and anti-inflammatory agents.

Although there are more than 400 Aloe species recognized, one plant, Aloe vera (L.) Burm. f., dominates both the commercial aloe market and the research literature. (This species is sometimes referred to by the extinct name, Aloe barbadensis Miller) Other Aloe species that have been extensively examined, especially in Asia, include Aloe arborescens Miller, and A. saponaria (Ait.)Haw. Such limited comparative studies that have been undertaken have shown that the biochemical composition of extracts from different Aloe species varies widely. As a result, biological responses obtained with material from one species, cannot automatically be ascribed to others. Nor have any studies been undertaken to determine whether factors such as geographical location, soil quality, fertilization or plant genetics influence biological activity. It is widely believed that the treatment and storage of the harvested leaves prior to, and during, processing influences its biological activity, and although processing has been the subject of much rhetoric between competing suppliers, controlled studies have not been undertaken. The products still hover on the edge of scientific respectability.

Aloes are succulent plants with characteristic thick fleshy leaves. The outer rind contains the bitter yellow sap that originates in the bundle sheath cells and is used for its purgative effects. The center of these leaves consists of a clear mesophyll gel. The mucilaginous texture of the mesophyll gel ensures that it is intrinsically soothing. As a result it has been used to treat superficial dermal inflammation resulting from a wide variety of causes. The gel has been especially useful in the treatment of radiation burns ranging from sunburn to X-ray and radium burns. Despite the anecdotal nature of much of this work, results are generally positive and the gel is widely employed. Indeed, it is rare to find a commercial ‘soothing’ preparation that does not contain ‘Aloe vera’ as one of its components. It may also have some ill-defined antimicrobial properties.

Aloe extracts are commonly made from the whole leaf, or alternatively, from the clear mesophyll gel. The composition of these two extracts differs significantly since the thick photosynthetic rind contains many components not present within the mesophyll. Aloe vera leaves are, however, little different from other plants in their basic composition. They consist primarily of a carbohydrate mixture with some proteins and a host of minor components such as steroids, anthraquinones, flavonoids, and chromones, as well as enzymes such as carboxypeptidases, superoxide dismutase and glutathione peroxidase.

Their cell walls contain celluloses, hemicelluloses and pectins while their major storage carbohydrate is either an acetylated mannan or a glucomannan. There may be a significant number of proteins within the gel. These have not been well characterized. From an immunological viewpoint, the most important of these proteins are the lectins.

Aloe gel

The central gelatinous portion of the aloe leaf is a translucent structure consisting entirely of mesophyll cells. These cells contain few organelles, primarily leucoplasts, and are completely filled with a very large vacuole containing a concentrated aqueous solution of a mixture of complex carbohydrates, especially acetylated mannans, and some low molecular weight solutes, especially calcium malate. The cell walls have a typical structure containing both celluloses and pectins. When aloe leaves are harvested and processed, the mesophyll cells rupture and the acetylated mannan solution is released. Soluble pectins and cell wall hemicelluloses are also present in this carbohydrate solution. Leaf extracts containing this carbohydrate mixture influence both innate immune mechanisms such as inflammation and macrophage function, as well as specific acquired immunity. These carbohydrate solutions may also contain small but significant amounts of protein.

The precise carbohydrate content of the aloe leaf gel varies according to the time of day. Aloes, as desert plants, take up carbon dioxide during the night and store it temporarily as malic acid. During the following day they convert the malic acid to carbohydrates. Thus the leaf is high in malic acid at dawn but this level drops steadily and carbohydrates rise during the day. As a result, the time at which the leaves are harvested will significantly influence the composition of the gel.

Acemannan

Acemannan is the name given to the acetylated mannan isolated from Aloe vera (). The predominant storage carbohydrate of Aloe vera, it consists of long chain polydispersed β(1,4)-linked mannan polymers with random O-acetyl groups. Acemannan has been claimed to possess many, if not all of the important biological activities of the aloe pulp. However it has proven exceedingly difficult to separate acemannan from contaminating protein. Likewise there are other complex carbohydrates present in most acemannan preparations. As a result, it is by no means proven that acemannan alone posseses the biological activities ascribed to it. Another cautionary note should also be made with respect to endotoxin content. It is difficult to produce aloe carbohydrate solutions free of contaminating endotoxin. Early studies on this material contained small but significant quantities of bacterial endotoxin and it is possible that some of the biological activities ascribed to acemannan may have been endotoxin effects.

Pectins

Aloe vera cell walls contain a unique pectin. This low-methoxy pectin contains up to 90% glucuronic acid. As a result it has unusual biological properties, such as the ability to bind and stabilize certain mammalian growth factors. Its presence in crude acemannan preparations may explain, in part, why these preparations can accelerate wound healing under certain circumstances.

Other carbohydrates

Other complex carbohydrates may be present in aloe gel extracts in small amounts and some of these may exert significant biological activity. For example Pugh and his colleagues have identified a high molecular weight polysaccharide from Aloe vera (aloeride) that is a very potent macrophage activating agent. Its molecular weight may be as large as 7 million. It contains glucose, galactose, mannose and arabinose and it is as potent as bacterial endotoxin at activating nuclear factor (NF)-KB in human macrophages. Aloeride also induces the expression of the mRNAs encoding Il(interleukin)-1p and TNF (tumor necrosis factor)-α to levels equal to those observed in cells maximally activated by bacterial endotoxin. Thus, although aloeride constitutes only 0.015% of dry weight of aloe gel juice, its potency may fully account for the macrophage stimulating activity of this juice. Limited studies have been conducted on the carbohydrates of other Aloe species ().

Low Molecular weight components

While the leaf gel consists primarily of a complex carbohydrate mixture, the green plant rind contains many complex organic compounds such as chromones, flavonoids and anthraquinones. The precise composition varies greatly between aloe species. Some of these molecules, especially the chromones and flavonoids, can have significant anti-inflammatory activity or antiviral activity.

Aloes and the immune system: Specific activities

Aloes and the immune system: Conclusion

There is no doubt that extracts of aloe leaf gels can exert significant anti-inflammatory activity. At the same time similar gels can activate macrophages and perhaps other cells involved in the defense of the body. Unfortunately the aloe preparations used for these studies have tended to be complex, ill-defined mixtures and it is therefore difficult to elucidate the biochemical pathways involved.

 

 

Selections from the book: “Aloes. The genus Aloe”. Edited by Tom Reynolds. Series: “Medicinal and Aromatic Plants — Industrial Profiles”. 2004.