The Exudate Compounds of Aloe and their likely Benefits in Gel or Whole Leaf Extract

The compounds in Aloe vera Exudate are often regarded as undesirable on account of their strong laxative action. Hence measures are usually taken to minimise the levels of these compounds in Aloe vera Gels and Juices that are intended for general health purposes. Such products do not generally cause any unwanted laxative effects. However, do any small traces of these compounds which remain in the products actually contribute positively to the biomedical activities of Aloe vera Gels and Juices? Do some individual members of this group of compounds perhaps lack any laxative effect at all and only contribute desirable, health-giving effects? These questions are discussed in this Newsletter.

Aloe Vera Exudate Compounds

The amazing array of active compounds in Aloe vera Exudate, are composed of phenols, including anthroquinones, anthrones and chromones, and are generally regarded as undesirable on account of their strong laxative action. Hence, definite measures are usually taken to minimize the levels of these compounds in Aloe vera Gels and Juices that are intended for general health purposes. In such products the precautions taken generally ensure that the user will not experience unwanted laxative effects. However, the interesting questions now arise as to whether (a) some small traces of these compounds which remain may actually be contributing positively to the important BioMedical activities of Aloe vera Gels and Juices (b) some individual members of this group of compounds, which may be similar to known laxative compounds, may lack any laxative effect at all and only contribute desirable, health-giving effects. We begin by considering further the nature of the compounds contained in this important but controversial fraction of Aloe.

The Phenolic Substances of the Exudate

All the names which have been given to this Fraction of Aloe are unsatisfactory. It is constructive to compare and contrast these alternative names. The name "Exudate Fraction" is really unsatisfactory because the actual leaf exudate seems bound to contain, in addition to the group of substances with which it is specifically associated, many of the non-phenolic substances which are also present in the rest of the leaf. The objection is therefore that this name fails to define specifically the range of substances concerned.

"Anthraquinone Fraction" is also unsatisfactory because the phenolic compounds present in the Exudate fall into a number of different classes of which "anthraquinones" are only one. As indicated above the others are anthrones and chromones. "Aloin Fraction" is even more unsatisfactory because substances termed "aloin" form just a sub-class of the anthraquinone fraction. Therefore, this name is even more narrow and specific than the previous one. This author therefore favours the use of the term "phenolic fraction", a term which effectively demarcates these substances from other classes of compounds.

Uses of Aloe Phenolics in the Ancient World

It appears likely that much, or even most, of the use of Aloe that is recorded from the Ancient World employed the Exudate and therefore depended principally upon the phenolic fraction. One reason for that was clearly that the Exudate was easy to collect without any special technology. Another was that the Aloe used was not necessarily Aloe vera - e.g. Socotrine Aloes, Aloe perryi, was almost certainly used. Any Aloe which did not produce a central "fillet" which could be cut out and separated from the rind, could only be used to obtain preparations which would have the Exudate Fraction present. The principle biomedical effects of Aloe known in the Ancient World appear to have been as follows.

1. cathartic, meaning a laxative
2. stomachic, meaning a medicine to improve stomach function
3. emmenagogic, meaning a promoter of menstrual flow
4. antihelmitic, meaning a worming preparation

The Ability of Phenolic Components to Contribute to the Overall BioMedical Actions of Aloe

Anti-Microbial Effects

Mostly it is the earlier research which focused attention upon the direct microbe-killing effects of the phenolic fraction. These effects seem to be clearly established. This anti-microbial action is clearly due to a cytotoxic action (i.e. a "toxic to cells" effect) from the relatively aggressive biochemicals such as aloin. In this respect the action of these substances would be much like any other bactericidal or disinfectant agent. One cannot be sure to what extent the bacterial cells are actually killed or just inhibited from growth and multiplication, but either way, the development of a run-away infection is avoided. References to this work have been included in Issue 9 of these Newsletters. However, the ability to kill micro-organisms is not what users of Aloe usually want. A disinfectant action is not what is required. Besides, this property originates from the biologically aggressive properties of the Aloe phenols and is associated with their toxic and laxative actions.

This action should be carefully distinguished from the immunostimulant effects of Aloe which help the body to reject infections by increasing the activities of the immune system. This action is more associated with the carbohydrate fraction of Aloe but it is even possible that some component or components of the phenolic fraction also act upon the immune system.

Do beneficial traces of some individual members of the Phenolic Fraction remain in Gel and Whole Leaf Extracts?

The literature contains many references to the Phenolic Fraction producing BioMedical effects in addition to the anti-microbial effects. Some papers refer to the likelihood that Aloe Gel does contain some minor quantities of phenolic compounds, such as barbaloin and aloe-emodin, at concentrations where they are devoid of over-stimulatory, chemically aggressive properties. Aloe Gel naturally contains only low levels of phenolics (which are mostly concentrated in the rind of the leaf). Therefore, it may not be necessary to process Gel for removal of the phenolics when this natural level can be kept sufficiently low. During commercial processing of Aloes, it is virtually impossible to prevent some contamination of the Gel with just a little of the exudate fraction which mainly resides in the rind. To keep it as low as possible, and so avoid the need for a carbon filtration step, the Gel is often hand-filleted.

Opinion differs as to whether the exudate components in the Gel should be seen just as an unwanted contaminant (because of the undesirable laxative action of aloin) or whether they should be welcomed in the tiny quantities in which they occur, for their positive effect in enhancing the effectiveness of the main leaf components. One pair of authors suggest that there may be a specific synergy between trace quantities of exudate compounds and the polysaccharide fraction of the Gel, i.e. (Heggers & Robson 1983, in "Nennemann, J., (Ed) "Traumatic Injury, Infection and other Immunological Sequelae" University Park Press, Baltimore pp 79-102.)

How Phenolic "Contaminants" may affect the BioMedical Properties of both Gel and Whole Leaf Extract

As mentioned, there is the likelihood of accidentally mixing into the Gel minor amounts of exudate whilst cutting and processing the leaf. Where this happens it raises the level of phenolics in the Gel well above the very low levels which this tissue naturally contains. This is best minimized by hand-cutting the Gel. When one comes to consider the Whole Leaf process, this is likely to involve a rather different final mix of phenolic trace contaminants from the Gel process. In the Whole Leaf process you have the initial extraction of Gel and rind together, giving a first extract which is rich in phenolics, followed by the removal of the phenolic components by carbon filtration. To whatever extent that this process is incomplete, the low concentrations of phenolic compounds which remain are likely to be of a composition characteristic of the carbon filtration process. Hence one would expect the Gel and the Carbon-treated Whole Leaf Extract to each bear their own individual "fingerprints" of phenolic substances at low concentrations. The detailed pattern of any residual phenolic components left under these conditions is, indeed, likely to be rather different from the Gel process, and may have different merits.

Such differences may or may not be shown to definitely favour the use of Whole Leaf Extracts rather than Gel for some BioMedical purposes but not others. More work needs to be done to find out and to quantify any such effects and to associate them with particular phenolic components.

Evidence for the Specific Efficacy of some Rind Components

Rowe T., Lovell. B., & Parks, L. (1941), in "Further Observations On The Use Of Aloe Vera Leaf In The Treatment Of 3rd Degree X-Ray Reactions" J. Amer. Pharm. Assoc. 30 266-269, concluded that an important component of the healing substances passes from the rind of the leaf into the Gel on standing. This conclusion was based upon the fact that, of their rats that were subjected to radiation burns, 100% healed faster when treated with the rind, compared to 64% that were treated with the Gel. They were forced to consider what healing substance or substances could be present in the rind which was or were absent from the Gel. They obtained different ratios of effectiveness between rind and Gel depending upon the time during which the rind and Gel were left in contact.

While this old work provides us with no more than an indication, the observations are quite compatible with the idea of a low molecular weight component (which could be a phenolic one) passing from rind to Gel in tiny quantities, but nonetheless having a synergistic effect with the other active components of the Gel, to produce markedly enhanced activity. It has to be stressed, however, that these ideas about exudate compounds in the Gel or Whole Leaf Extract have not yet been proven.

The possible involvement of components of the phenolic fraction in the immuno-stimulant action has been found by monitoring the processing of Whole Leaf Aloe. If Whole Leaf Extract is tested for immuno-stimulant activity before carbon filtration, it is found to be very highly active. About one third to half of that activity is then lost during the carbon filtration step. It is tempting to conclude that this is due to the removal of immuno-active phenols. However, full proof of this is awaited from future work, because carbon filtration probably does remove some components other than just the phenolics.

Further evidence can be found by considering individual medical conditions in which phenolic constituents, whole exudate, or phenolic "contaminants" in a Gel or Whole Leaf Extract have been shown to have (or contribute to) efficacy.

Skin Conditions

Dermatitis in dogs had been investigated in several papers and found to be helped very significantly by preparations of Aloe containing the phenolics. In the study of skin disease in humans, there are several papers to cite, such as;

Cole H.N. & Chen K.K. (1943) "Aloe vera in Oriental Dermatology", Archives of Dermatology and Syphilology 47 250.

Anton, R. & Haag-Berrurier, M. (1980) "Therapeutic Use of Natural Anthraquinones for other than Laxative Action" Pharmacology 20 (Suppl 1) 104-112 also discuss the use of anthraquinones from various plant sources in the treatment of conditions such as psoriasis.

However, the usefulness of gel in psoriasis or related conditions does not appear to have been clearly established, but the literature suggests that if Aloe has efficacy at all in that connection, this may be due to the phenolic fraction or residual traces of it. Treating a specific named skin disease is very different from using Aloe for general skin improvement, which is a recognised use for Aloe. Hence, when trying the use of Aloe for skin conditions, either Aloe Gel or Whole Leaf Extract, one should perhaps aim to use preparations containing more than usual amounts of phenolics.

In the very different matter of leg ulcers, the paper by Zawahry et al (1973) still appears to stand as the most interesting and, indeed, promising publication about Aloe in surface disease, (even though more than just the skin is involved).

"The Use Of Aloe In Treating Leg Ulcers And Dermatoses" (1973) El Zawahry, M., Hegazy, M., Helal, M. Int. J. Dermatology 12 68-73.

Burns

Early studies by Crewe (1939) had related to burns and had used the phenolic fraction in the form of powdered Curacao Aloes (which is Aloe vera). The fact that the phenolics appeared to be effective in this context is especially interesting because it seems to imply that an anti-inflammatory, healing, or possibly even immunostimulant effect might be involved.

Heggers and Robson (1983) also take up that point. They suggested that the effect was due to anthraquinones and related compounds, such as aloin and aloe-emodin, present in the Gel, acting as "false substrate inhibitors", blocking synthesis of the prostaglandin hormones. This means that they are combining with the enzymes to prevent them from catalysing prostaglandin formation.

Peptic Ulcer

In work done by Blitz and colleagues in Florida (1963) 12 patients with peptic ulcer were selected and Aloe vera gel was the sole source of treatment. Extremely positive healing effects were seen and patients recovered well, as detailed in Issue 3. From that work alone there would be no reason to think that the phenolic fraction is involved in the beneficial action. However, in Japanese work on peptic ulcer at least one component of the phenolic fraction was recognised as being important. The Japanese work, done between 1970 and 1978, is significant insofar as it identifies in several papers that a factor in Aloe which diminishes stomach secretion is the phenol, aloenin. They obtained this from Aloe arborescens. Aloenin is one of the individual components of the phenolic fraction. It is a phenolic compound of the type called by chemists a "quinonoid phenylpyrone".

Aloenin And Aloe-Ulcin From A Arborescens Inhibit Gastric Secretion. (1970) Yamamoto I. J. Med. Soc. Toho Jpn. 17 361.

"Aloenin, a New Bitter Glucoside from Aloe Species" (1972) Suga, T., Hirata, T., & Odan, M.. Chem. Letters, Chem. Soc. Jpn., 547-550.

The fact that aloenin has this property means that it would have an action not unlike that of a drug such as cimetidine, which has a huge usage as a chemical drug for the treatment of peptic ulcer by suppression of stomach secretion and, as a natural product, might conceivably replace it after sufficient testing. These Japanese findings show that, once again, a component of the phenolic fraction of an Aloe species seems to have an important biomedical effect. It will be of interest to find out whether this effect on peptic ulcer is synergistic (synergy is working together to produce a greater effect) with the action of the non-phenolic Aloe components. If it were to be so it would raise once again, the question of using a combined treatment in which Aloe Gel would be enriched with aloenin, either in one and the same product, or in complementary products. However, most reports of aloenin related to the species arborescens, not vera.

Tumours

The first definite reference to an anti-cancer effect of Aloe which this author has found is dated 1969 in a paper by Soeda of Japan.

Extract Of Cape Aloes Inhibited Sarcoma 180 And Ehrlich Ascites Tumours. Soeda, M. (1969) J. Med. Soc. Jpn. 16 365.

There was a further such reference by other authors from Japan in 1972. These were reports on the use of Aloe to treat animals with tumours, and showed that the tumours were inhibited. Papers appeared by Yagi et al (1977), Suzuki (1979), Imanishi et al (1981), Yoshimoto et al (1987) and Imanishi (1993). This work has been considered in Issue 6 of these Newsletters.

This work all concerned animal tumours and was carried out either by treating animals that were carrying tumours and demonstrating inhibition of the tumours, or by studying the immunological aspects of the problem, for example, by looking at the activation of the animals T-lymphocytes of the type which would have the job of tackling the tumour cells.

Some of these papers were primarily concerned with isolating and studying fractions of the polysaccharide from Aloe and finding out which ones exhibited anti-tumour effects. One interesting aspect of the above is that the work of Soeda (1969) was carried out using Cape aloes (Aloe ferox) and preparations of Cape Aloes usually contain or consist of the phenolic fraction. Much of the other work used Aloe arborescens and the work is generally carried out with Whole Leaf Extracts. There is once again room for speculation that components of the phenolic fraction may have some contributory role in the BioMedical activity.

However, very often the material used in the studies was a separated fraction isolated from an original Whole Leaf Extract and composed either of polysaccharide or glycoprotein. In these cases it is more probable that the phenolic components were largely or wholly removed and that the activity then being measured resided in these higher molecular weight biomolecules.

Arthritis

Human Clinical studies on Aloe in arthritis are lacking. Animal work by Professor Davis and co-workers, of the Pennsylvania College of Podiatric Medicine, Philadelphia, U.S.A. (1985), (1986) has provided some positive results, but used either phenolic from Aloe, or whole homogenised Aloe, demonstrating anti-arthritic effect. Hence, in both these papers, phenolic fraction was either the medicine used, or the entire leaf, containing the phenolic fraction, was present.

Hence, once again, the prospect that individual components of the phenolic fraction may be needed for some of Aloe's BioMedical properties, in this case arthritis, raises its head. It is an issue which will require full consideration. Such evidence that we have certainly contains the strong suggestion of a role for Aloe in arthritis, but the presence of these phenolic components may, indeed, be required. This position with regard to arthritis is of particular interest because it suggests that the key BioMedical effects of Aloe are involved - especially the anti-inflammatory and perhaps the immunostimulant effects.

Inflammation

One major component of the arthritic condition is inflammation. In the hands of Davis, Agnew & Shapiro (1986), an animal model of arthritis responded positively to Aloe phenolics, in particular, anthraquinone. Hence it is reasonable to consider whether the phenolics do contribute generally to Aloe's anti-inflammatory action. Recently, there have been several reports of readily isolated low molecular weight anti-inflammatory substances in Aloe vera and these have been undergoing tests in a number of companies. These may include phenolic active principles.

"Antiarthritic Activity of Anthraquinones Found in Aloe for Podiatric Medicine" Davis, R.H., Agnew, P.S. & Shapiro, E. J. (1986) Am Pod. Med. Assoc. 76 (2) 61-66

Non-Insulin Dependent Diabetes

Whilst this subject has been treated in Issue 7 in respect of the action of Aloe as a whole, some references suggest or imply in their presentation that phenolic components may be involved. These include;

"Aloe vera: A Natural Approach for Treating Wounds, Edema and Pain in Diabetes" (1988) Davis, R.H., Leitner, M.G., & Russo, J.M. J. of the American Podiatric Medical Assoc. 78 (2) 60-68.

"Aloe Vera and Gibberellin. Anti-Inflammatory Activity in Diabetes." (1989) Davis RH & Maro NP J Am Podiatr Med Assoc Jan 79 (1) 24-26

Another paper which is enormously encouraging towards the idea that aloes are an effective remedy against noninsulin dependent diabetes, and in which it was very clear that the Phenolics were specifically involved is;

"On the Mechanism of the Hypoglycaemic Effect of a Plant Extract." (1985) Al-Awadi FM, Khattar MA & Gumaa KA Diabetologia Jul 28 (7) 432-4

Some surprise arises because the source of the Aloe material being used was "bitter aloes", otherwise known as "drug aloes", and these names represent the Exudate. Without a doubt more trials, and, in particular, a larger trial, preferably organised on a double-blind basis, are needed to clearly establish aloes as an effective remedy and also to establish just what part the phenolics are playing. This matter should not be left in abeyance because of its potential importance. If the Aloe material used is, indeed, effective against NIDD, then we need to know which subfraction of the phenolic fraction is responsible. We do not know at the present time. Indeed, one cannot be completely sure that the effect is caused by an anthraquinone or phenolic component at all, since the sap of the plant - otherwise called the exudate - whilst it is a concentrate of anthraquinones and phenolics, also contains some of the same components which are in the gel or "de-aloinized".