aloe

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By H. , Ph.D.

An examination of the biological activity of steroids and synthetics

revealed that they are both active yet toxic. In the search for natural

substances, such as vitamins and amino acids, that have biological activity,

we serendipitously discovered that Aloe vera had many biologically active

compounds that had anti-inflammatory, wound healing, analgesic and

anti-arthritic activity.

Mannose and glucose are the most significant sugars found in the Aloe vera

gel, and they can be used to assay the activity of Aloe vera. The gel

contains important sterols which can have anti-inflammatory activity. Amino

acids such as tryptophane and phenylaianine reduce inflammation. Studies

have shown that vitamin C & B complex can maintain adrenalectomized animals,

and that minerals such as zinc are very important in wound healing.

Anthraquinones have good anti-inflammatory activity, but their activity is

usually obtained by working through an inflammation pattern. Salicylic acid

and aspirin are also highly biologically active.

The rind is the manufacturing plant for carbohydrates, fats, proteins and

vitamins. These Aloe vera constituents are transported throughout the leaf

by the phloem, and other materials are brought up from the roots by way of

the xylem. These two mechanisms aid in transporting the Aloe vera under the

influence of the wind. Mucilage was once thought to take part in this

transport process, but researchers now feel that it acts as a container for

the gel fillet or the storage of Aloe vera.

If one takes the liquid mucilage and freeze dries it, one finds that the

mucilage looks and acts like a bandage. It has occlusive “coverlike”

properties as well as biological activity. The topical anti-inflammatory

activity of mucilage at the 1% dosage is 3.8% in decreasing edema, whereas

at the 5% dose level, it is 33.7%.

A consideration of the sol-gel transformation becomes very evident as an

animal bites the Aloe leaf. The sol which is a colloidal system under the

influence of many factors can be converted into a colloidal gel. If this

system could be transported to the human wound, one would have an excellent

topical wound healing treatment.

In the Aloe leaf synthesis, carbon dioxide and water are converted to an

“active carbon that is used to make carbohydrates, lipids, protein and

vitamins. The Aloe vera cell, visible at a magnification of about 40,000, is

surrounded by a cell wall, has a large nucleus and two cell membranes the

cytoplasm of which manufacturers mucopolysaccharide. The mucopolysaccharide

is stored within the lumen of the cell.

Aloe vera could prevent adjuvant arthritis 72%, and cause a regression of 22

to 26% at a dosage of 150 mg/kg per day. In another experiment, we proved

that Aloe vera was effective in reducing inflammation over a broad spectrum

of irritants in experimental animals. The percent inhibition by Aloe vera

ranged from 76.9% against gelatin to 22.7% against dextran. In evaluating

vitamin C’s influence on localized adjuvant arthritis, we found that it

could reduce edema 80%, inhibit PMN infiltration, and decrease the pain

induced by the adjuvant arthritis. However, there was no influence on the

paw temperature. Anthranilic acid, a metabolite of tryptophane, could

inhibit PMN infiltration as was evident in the peritoneal fluid of adjuvant

arthritic rats.

The topical treatment of adjuvant arthritis with combined Aloe, RNA and

vitamin C produced a 25.2% prevention inhibition and 45.1% regression

inhibition at a dosage of 1.5% concentration of each.

Phenylaianine synergized with hydrocortisone acetate in reducing localized

edema. We also obtained a good vehicle response on anti-inflammatory

activity using Aloe vera for hydrocortisone acetate. The combination of Aloe

vera and hydrocortisone was definitely additive in nature. We observed the

vehicle effect of Aloe vera for hydrocortisone acetate on inhibiting the

infiltration of PMN’s as well as the topical application of the steroid.

Aloe vera is also a good vehicle for vitamin C and other important agents.

Tryptophane and phenylalanine had good local anti-inflammatory activity in

inhibiting PMN infiltration. In fact, the inhibition effect approaches that

of the steroid. While phenylalanine was able to inhibit granuioma tissue

weight in adrenalectomized Tanimals synergistically with cortisone,

tryptophane did not synergize with the steroid.

When we placed a cotton pellet under the skin of a rat we found that Aloe

vera was unable to inhibit the growth of granuloma tissue. Aloe vera had no

antifibrosis effect over a dosage range of 50 to 400 mg/kg administered for

12 days.

While Aloe vera had no chronic anti-inflammatory influence, we wondered if

it could inhibit the detrimental effects of the steroid on wound healing.

Aloe vera could inhibit edema in diabetic animals in a dose-response fashion

up to 80% over a dosage range from 10 to 100 mg/kg.

A similar response was obtained in diabetic animals by Aloe vera in

inhibiting the infiltration of PMN’S. Aloe vera definitely can block the

vasoactive substances responsible for inflammation, can constrict small

blood vessels, can block PMN filtration, as well as inhibit production of

oxygen radicals.

We evaluated the influence of mucilage in Aloe vera on skin penetration of

5% trypan blue over six hours. We found that Aloe vera at a 10% dose could

increase the trypan blue penetration 24%. However, 10% mucilage was

occlusive, that is it acts as a cover for wounds and blocks the penetration

of trypan blue. A combination of Aloe vera and mucilage revealed that the

mucilage could block the penetrating ability of Aloe vera. Mucilage acts as

a cover for wounds but does not increase the penetrability through the skin.

The effect of Aloe vera on skin fibroblasts was measured by Danhof in 1983

(Danhof 1987). He found that tritated thymidine uptake by skin fibroblasts

was increased in a dose-response fashion by Aloe vera. He also found that

the anthraquinones in the yellow sap killed the fibroblasts. This “killing

of fibroblasts” has potential as an anti-inflammatory assay if Aloe vera was

used to protect against this “killing effect.”

Years ago we felt that wounds should not be covered. However, we found that

dry wounds drop, and prevent the migration of cells and the influence of

wound healing growth factors. With Aloe vera acting as a cover, the wound

remains moist, and there is an excellent migration of epidermal and

fibroblast cells. So there is an increase in covered wound healing over that

of uncovered wounds. Aloe vera increased the wound healing over a dosage

range of 1 to 100 mg/kg in a dose-response fashion.

This was the first study that demonstrated that Aloe vera was effective in

animals.

Aloe vera is a modulator. It has an inhibitor system capable of blocking the

immune system observed in the adjuvant arthritic animal, and it can block

the mediators responsible for inflammation.

Aloe vera also has a stimulatory system in which it can increase antibody

production and stimulate wound healing by means of growth factors such as

gibberellin, auxin and mannose phosphate. The isolation of the wound healing

and anti-inflammatory activities using the 50% ethanol extraction of Aloe

vera revealed that the supernatant contained 78% of the anti-inflammatory

activity whereas the precipitate had only 32%. On the other hand, the

supernatant had 0% wound healing activity whereas the precipitate had 160%

wound healing activity in reference to the original Aloe vera. This 160%

value is likely due to the fact that the anti-inflammatory activity is

masking some of the wound healing effect seen in the original Aloe vera.

All of our studies seem to indicate that Aloe vera is both orally and

topically active on wound healing and inflammation even in the diabetic

animal. For example, studies show that Aloe vera can improve wound healing

in the diabetic in a clear cut dose-response fashion over a dosage of 1 to

100 mg/kg.

Gowda demonstrated that mannose phosphate is the significant constituent in

the 50% Aloe vera extract (Gowda 1979). At the same time, showed that

the mannose phosphate will bind to the insulin like growth factor receptor

( 1987). Willenberg’s study exhibited the anti-inflammatory activity

of mannose phosphate (Willenberg 1989). Its ability to improve wound healing

is evident.

The effect of mannose phosphate on topical croton-oil-induced inflammation

was dose-related. The plateau of the dose-response curve was seen, however,

at 25% inhibition. Glucose-6-phosphate had no effect and served as a

control. Mannose phosphate improved wound healing in a dose-response

straight-line fashion, but not response was seen with glucose-6-phosphate.

The mannose phosphate of Aloe vera activates the insulin like growth factor

receptor.

The “Aloe vera molecule” consists of a protein at one end and

mannose-6-phosphate at the other end. The polysaccharide chain contains one

glucose which is covalently linked to the protein with six mannose sugars

moving toward the insulin, like the growth factor receptor of the

fibroblast. The “Aloe vera molecule” can stimulate the fibroblast to

increase collagen and proteoglycans.

We feel that the protein part of the Aloe vera molecule acts to guide the

polysaccharide chain into the receptor. The mechanism of action of Aloe vera

at the present time seems to inhibit pain and inflammation, but also can, by

means of the growth factors, stimulate the fibroblast to increase wound

tensile strength.

We have developed a wound tensile strength assay in which the length of the

curve extends from day three to day ten. A dose-response relationship with

Aloe vera on wound tensile strength was obtained on a two-day treatment as

well as on a four-day treatment basis at doses of 50 to 300 mg/kg per day.

The slopes of both curves were similar. However, we have decided to use the

four-day treatment as the curve on which to best assay Aloe vera on wound

tensile strength. Gibberellin, a plant growth hormone, stimulated wound

healing in a dose-response straight-line fashion over a dosage range from 2

to 100 mg/kg. Auxin was also shown to have good biological activity.

Gibberellin could also block PMN infiltration even in diabetic animals up to

60%.

Aloe vera may have an additive or a synergistic relationship with over 100

compounds to produce biological activity. It is possible that Aloe vera acts

as a kind of conductor which produces music with an orchestra of many

biological active ingredients. It seems presumptuous for us to consider, or

even to postulate that any one substance is responsible for the biological

activity seen in the Aloe vera gel.

We made an air pouch in animals by administering 30 ml of air under the

skin. In seven days we administered 1% carrageenan into the pouch, and two

hours later we administered 10% Aloe vera to determine what effect Aloe vera

would have on the air pouch synovium.

We found that Aloe vera could stimulate the pouch wall weight by increasing

the number of fibroblasts. This agrees with previous findings that the

alcohol precipitate of Aloe had its greatest effect on wound healing by

stimulating the fibroblast. Aloe vera decreased by 60% the mass cell count

and wall vascularity.

The effect of Aloe vera on a 1% carrageenan-irritated simulated joint

synovium model proves conclusively that Aloe vera stimulates the

fibroblasts, as seen in the wound healing studies, and inhibits

inflammation, as evidenced by the decrease in vascularity and the reduction

in mass cell count.

We have shown that some of the constituents of Aloe vera have biological

activity similar to amino acids, vitamin C and growth factors like

gibberellin and Auxin. Some attention was given to how the Aloe leaf makes

and stores the gel. Mention was also made of the fact that we have seen what

we call the “Aloe vera Cell” in our laboratory at 40,000 magnification. In

addition we have shown that the “Aloe vera molecule” probably does not act

alone, but rather acts in either an additive or synergistic fashion with

some of the 100 constituents of the Aloe vera.

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REFERENCES

Danhof I 1987. Aloe Through the Ages, Volume 1. Omnimedicus Press.

Gowda D; Neelisiddaiah B; Anjaneyalo Y 1979. Structural studies of

Polysaccharides from Aloe vera Carbohydrate Research. 72:201.

, D; Edman JC; Strand-ring DN; Fried VA; MC; Roth RA; Rutter WJ

1987. Insulin-Like Growth Factor 11 Receptor as a Multifunctional Binding

Protein. Nature 329:301.

Willenburg DO; Parish CR; Cowden WB 1989. Phospho-sugars are Potent

Inhibitors of the Central Nervous System: Inflammation FASEB 3: 1968.