Saccharides

Recent research on A. vera has focused on the glycoprotein, mucopolysaccharide, and polysaccharide constituents. Aloe contains the polysaccharides galactose, xylose, arabinose, and acetylated mannose. The latter, similar to guar and locust bean, has received considerable clinical research attention as an antiviral and immunopotentiating agent, especially in the treatment of acquired immunodeficiency syndrome (AIDS). Acemannan is a water-soluble, long-chain polydispersoid β(1,4)-linked mannan polymer interspersed with O-acetyl groups found mainly in aloe gel.⁶

Prostanoids

Several prostanoid compounds have been discovered in A. vera extracts.⁷ The conversion of essential fatty acids to prostanoids by the enzyme cyclooxygenase in a plant such as A. vera is rare. The major unsaturated fatty acid in the plant is γ-linolenic acid (C18:3), which can be converted to icosatrienoic acid, the precursor to prostaglandins of the 1 series. The 1 series prostaglandins are known to exert more favorable effects on inflammation, allergy, platelet aggregation, and wound healing. The presence of γ-linoleic acid or prostaglandins, or both, in a stable medium, along with inhibitors of thromboxane synthesis, may be another important chemical characteristic of aloe responsible for its antiinflammatory and wound-healing effects.

Superoxide Dismutase

Extracts from the parenchymatous leaf gel and the rind of aloe (A. barbadensis Miller) have been shown to contain seven electrophoretically identifiable superoxide dismutases (SODs). Two of these seven are mangano SODs, whereas the other five activities are cupro-zinc SODs.⁸

Other Constituents

Other biological active compounds found in A. vera include the following:

• A serine carboxypeptidase

Box 64-1 provides a partial listing of the remarkably diverse range of compounds isolated from A. vera.²^–⁵

History and Folk Use

A. vera has a storied history of use. Mesopotamian clay tablets dated 1750 BC indicate that A. vera was used for medicinal purposes. Egyptian records from 550 BC also mentioned aloe for infections of the skin. The ancient Greeks were also aware of aloe’s medicinal effects, since both Pliny (23-79 AD) and Dioscorides (first century AD) wrote of aloe’s ability to treat wounds and heal infections of the skin. A. vera is still widely used in many traditional systems of medicine. In India, for example, in addition to external applications, aloe (whole leaves, the exudate, and the fresh gel) is used as a cathartic, stomachic, and anthelmintic. A. vera has been adopted into their materia medicas by many cultures of the world.¹

In the United States, the history of aloe can be traced as far back as the United States Pharmacopoeia of 1820, where a number of aloe preparations were described. Most of these preparations were designed to take advantage of aloe’s laxative effects. By the early 1900s, more than 27 different aloe preparations were in popular use. In 1920, aloe began being cultivated for pharmaceutic use.⁴

A major development in the modern use of aloe occurred in 1935, when a group of physicians successfully used the fresh juice to treat a patient with facial burns due to radiographs.⁹ The relief offered by aloe in the topical treatment of burns, minor irritations, skin ulcers, and other skin disorders is a major reason why companies supplying dermatologic and cosmetic products have incorporated aloe into many of their formulations.

Although more and more of aloe’s medicinal effects are being confirmed, it is still predominantly administered without direct medical supervision. Therefore, the history and folk use of aloe are continuing to evolve.

Pharmacology

The pharmacology of aloe is surprisingly diverse—its laxative, immune potentiation, antimicrobial, and wound-healing activities help explain its wide-ranging folk and clinical applications.

Gastrointestinal Effects

Laxative Effects

Although physicians have prescribed the whole aloe leaf as a cathartic for more than 2000 years, it was not until 1851 that the active principle aloin was discovered.¹ In small doses, aloin acts as a tonic to the digestive system, giving tone to the intestinal muscle. At higher doses, it becomes a strong purgative. Its actions are most obvious on the large intestine, where it increases colonic secretions and peristaltic contractions. In combination with strychnine and belladonna, aloin became one of the most popular laxatives for chronic constipation for many years. Because aloin often causes painful contractions, other anthraquinone laxatives like cascara and senna are now much more popular.^10,¹¹

A substantial amount of research activity continues in an effort to understand the laxative effects of aloe. Research using the rat large intestine showed that the increase in water content of the large intestine induced by barbaloin preceded the stimulation of peristalsis, attended by diarrhea. Therefore, it was suggested that the increase in water content was a more important factor than the stimulation of peristalsis in the diarrhea induced by barbaloin.¹² Further studies by the same researchers suggested that aloe-emodin-9-anthrone (AE-anthrone) produced from barbaloin in the rat large intestine might be the actual chemical mediator of this effect. AE-anthrone not only caused an increase in the intestinal water content but also stimulated mucus secretion.¹³

Bowel Detoxification

In 1985, Bland ¹⁴ reported the effect of orally consumed A. vera juice on urinary indican, gastrointestinal pH, stool culture, and stool specific gravity in a semi-controlled study of 10 (5 men and 5 women) healthy human subjects.¹⁴ Urinary indican (see Chapter 30) is used as an indicator of the degree to which either dietary protein is malabsorbed or intestinal bacteria are engaged in putrefactive processes. After a full week of drinking 6 oz. of A. vera juice three times daily, urinary indican levels decreased one full unit. This suggests that regular A. vera juice consumption can lead to improved protein digestion and assimilation or reduced bacterial putrefaction, or both.

Inhibition of Gastric Acid Secretion

With Heidelberg gastric analysis, A. vera juice was shown to increase gastric pH by an average of 1.88 U. This supports the findings of other researchers that A. vera gel can inhibit the secretion of hydrochloric acid. The Heidelberg test also demonstrated that A. vera juice can slow down gastric emptying, possibly leading to improved digestion.

Six of the 10 subjects showed marked alterations in stool cultures after the week long study. This implies that A. vera juice may exert some bacteriostatic or fungistatic activity. In the four subjects with positive cultures for yeast, there was a reduction in the number of yeast colonies.

Stool specific gravity was reduced after the week of drinking A. vera juice. This implies improved water retention, yet none of the subjects complained of diarrhea or loose stools.

Immune-Enhancing and Antimicrobial Activity

Immunologic Effects

Antibacterial and Antifungal Activity

Aloe demonstrated activity against many common bacteria and fungi in several studies. In a detailed review of these studies, the researchers assayed the antimicrobial properties of an A. vera extract and reviewed the work of others.¹⁵^–¹⁷ Both mean inhibitory and mean lethal concentrations were determined and compared with silver sulfadiazine (SSD), a potent antiseptic used in the treatment of extensive burns. As shown in Table 64-1,¹⁹ the antimicrobial effects of A. vera compare quite favorably with those of SSD. A 60% A. vera extract was found to be bactericidal against Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia marcescens, Citrobacter spp., Enterobacter cloacae, Streptococcus pyogenes, and S. agalactiae. Concentrations of 70% aloe were bactericidal for Staphylococcus aureus, 80% for E. coli, and 90% for S. faecalis and Candida albicans. Organisms inhibited in other studies include Mycobacterium tuberculosis, Trichophyton spp., and Bacillus subtilis.^2,^4,⁵ The antimicrobial activity against common skin pathogens of A. vera gel in a cream base was shown to be slightly better than SSD in agar well diffusion studies.¹⁹

TABLE 64-1 Antimicrobial Effects of Aloe Vera Extract in Cream Base Compared with Silver Sulfadiazine in Agar (AgSD) Well (6-mm) Diffusion

ORGANISM	ALOE VERA	AgSD
Gram-negative
Escherichia coli	16	12
Enterobacter cloacae	14	12
Klebsiella pneumoniae	14	6
Pseudomonas aeruginosa	17	12
Gram-positive
Staphylococcus aureus	18	12
Streptococcus pyogenes	16	12
Streptococcus agalactiae	16	12
Streptococcus faecalis	6	11
Bacillus subtilis	19	14

Inhibition zones measured in millimeters.

Data from Robson MC, Heggers JP, Hagstrom WJ. J Burn Care Rehabil 1982;3:157-162.

Antiviral Effects

Acemannan (acetylated mannose) in injectable form has been approved for veterinary use in fibrosarcomas and feline leukemia. Its action in feline leukemia is quite impressive. Feline leukemia, like AIDS, is caused by a retrovirus (feline leukemia virus). The virus is so lethal that once cats develop clinical symptoms, they are usually euthanized. Typically more than 70% of cats die within 8 weeks of the onset of clinical signs. In a study of 44 cats with clinically confirmed feline leukemia, acemannan was injected (2 mg/kg) weekly for 6 weeks and the cats were reexamined 6 weeks after termination of treatment.¹⁸ At the end of the 12-week study, 71% of the cats were alive and in good health.

Acemannan demonstrated significant antiviral activity against several viruses, including feline AIDS, human immunodeficiency virus type 1 (HIV-1), influenza virus, and measles virus.²⁰^–²²

Immune Enhancement

Acemannan is a potent immunostimulant.^18,²³^–²⁵ Among the effects noted for acemannan are the enhancement of macrophage release of interleukin (IL)-1-α, cytokines, tumor necrosis factor, and nitric oxide release, as well as phagocytosis and nonspecific cytotoxicity. Acemannan also enhances T-cell function and interferon production, although these actions may also be due to enhanced macrophage function. Macrophage production of cytokines IL-6 and tumor necrosis factor-α were dependent on the dose of acemannan provided. These effects can be substantial. For example, in one study, acemannan was shown to enhance the macrophage respiratory burst (two-fold increase above the media controls), phagocytosis (45% compared with 25% in controls), and killing of C. albicans (38% killing of C. albicans compared with 0% to 5% killing in controls).²⁶