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Research by Robert H. Davis, Ph.D.
The
Aloe leaf has polysaccharide in the
parenchymal cells which is used by
the plant for energy. Mucilage is a
different storage form. All
polysaccharides are not the same.
When mucilage is placed over a wound,
the wound remains moist and does not
drop as does dry wounds. Epidermal
and fibroblast growth factors come
from the mucilage and stimulate the
fibroblast directly for growth and
repair. The cells as a result
migrate within the wound in a proper
manner to increase wound healing.
The occlusive nature (cover) of
mucilage increases wound healing
from a mechanical and endocrine
viewpoint. Mucilage is also a good
anti-inflammatory agent. Some
polysaccharides are immune
stimulatory and this immune property
improves wound healing probably
through the macrophage. The big
polysaccharides appear to be immune
stimulatory whereas the smaller ones
have anti-inflammatory activity.
When an animal bites into the Aloe
leaf, a hole is made in the leaf so
that there is opportunity for the
gel fillet to leak to the outside.
However, this does not occur. The
mucilage in combination with the
Aloe gel hardens which seals the
hole. Mucilage always hardens and
acts as a container for the inner
gel fillet. The transformation which
occurs here is a sol-gel
transformation of mucilage. Aloe
vera tends to improve the
penetration of water whereas
mucilage tends to block the escape
of water from a wound. We have been
able to transfer the sol-gel
transformation of mucilage and Aloe
to an animal wound in which it
improves an incisional wound some
130%. If Aloe and mucilage are
placed between two sticks, it takes
some 1200 gms of force to pull the
sticks apart.
Wound healing
does not just require immune
stimulation by polysaccharides but
Aloes healing comes from growth
factors, amino acids, glycoproteins,
gibberellin, auxin and minerals such
as zinc as well as polysaccharides.
These biologically active agents
synergize to give us the miracle of
Aloe vera. Polysaccharide is not a
magic bullet in that these other
biological agents make major
contributions to the biological
activity of Aloe vera.
In the making of Aloe vera, two
major processing procedures are used
by the Aloe industry to give us Aloe
vera. The fillet method removes the
rind by a mechanical means and the
fillet is washed. The whole leaf
method grinds up the whole leaf and
removes the rind by filter. The
anthraquinones are removed by
charcoal. The amount of aloin left
is less than 5 parts per million.
This amount is not detectable by the
deification reflex. When the Aloe
vera is freeze dried for both the
fillet and whole leaf methods and
the powders are stored on the shelf
for eight years, no difference was
recorded in biological activity.
Both methods yield the expected
activity that was recorded in the
beginning. Processing of Aloe vera
is supposed to breakdown the
polysaccharide polymer (depolymerase
enzyme) into fragments that have
little or no activity. This may or
may not be true as we have not seen
the evidence. However, if it is true
in Aloe vera, to assume that the
smaller polymers resulting from
enzyme breakdown of the
polysaccharide do not have
biological activity is a presumption.
In fact, there are a number of small
ploymers that have great biological
activity and are immune stimulators
which are being sold successfully on
the open market. The breakdown of
the polysaccharide in Aloe by
enzymes must be presented and the
resulting polymers must be evaluated
across the board for biological
activities using the original Aloe
vera as the control test substance.
In all the work that has been done
with the polysaccharide, we have
never seen Aloe vera as the test
control to which the polysaccharide
is compared. These things must be
done before we claim that the
various polysaccharides are the
magic bullets. Are they much more
potent than the mother Aloe vera
from which they were extracted? This
must be shown by peer review.
Aloe vera contains a large
polysaccharide molecule which we
have called the conductor. This
molecule leads the many biologically
active substances into a symphony of
biological events to heal wounds,
reduce inflammation and eliminate
pain. The conductor molecule fits
into the fibroblasts, similar to a
lock and a key mechanism so as to
set up a cascade of important
biological events, supported by Aloe
substances which are part of the
orchestra. The polarity of water is
needed for the polysaccharide to
communicate with the active
substances to synergistically
achieve the maximum desired benefits.
We opposed
the theory that there is only one
active molecule (a polysaccharide)
responsible for all its beneficial
effect. We are convinced
that all the biologically active
substances in Aloe are necessary to
achieve the maximum-end- benefit.
Only Aloe can attach the entire
spectrum of human conditions because
specific synergisms are brought into
sharper focus. We have observed that
if the polysaccharide from Aloe is
washed extremely well - that is to
remove all agents from it, the
polysaccharide has very little
biological activity. In fact, what
is called polysaccharide is a
polysaccharide with active orchestra
members attached to it giving it
biological activity along the lines
we have discussed. If the
polysaccharide is prepared in
different ways, some activities may
be lost and others remain. The
“magic bullet” apparently requires a
communication with orchestra agents
to have its best influence.
Aloe vera is a biological vehicle
in that it acts as a physical or
physiological carrier for active
biological agents but, also adds
biological activity to the test
agent no matter what the
pharmacologic agent under
consideration is. In effect, it is a
physical carriage plus added Aloe
vera activity. This is the orchestra
of active substances surrounding the
polysaccharide conductor. Thus the
Aloe vera can add to the biological
activity of most test substances.
Substances can by synergized and put
into Aloe for a biological vehicle
effect. Can the conductor (the
polysaccharide) do this most
important biological vehicle effect
by itself without the surrounding
orchestra agents? I think not. It
needs the rest of the team. If it
can, it needs to be published as
data under peer review and not just
a “commercial blurb” put out to stir
up controversy. Aloe vera
contains water soluble compounds
such as amino acids, enzymes and
carbohydrates as well as oil soluble
compounds such as vitamins, sterols
and anthraquinones. Possibly,
pharmacologic agents of both
solubility’s can be placed in Aloe
and carried through the skin to
blood vessels. In an indirect way,
the biological agents in Aloe can
help the conductor (the
polysaccharide) produce the
biological response at the cell
receptor.
To suggest that the polysaccharide
works alone is presumptive and it is
unwise to call it the magic bullet.
The polysaccharide has biological
activity but not of the order
obtained by synergizing with the
surrounding biological compounds.
Aloe vera has been called a
modulator in that it brings
biological systems into balance.
Using the Gowda 50% ethanol
extraction procedure on Aloe vera,
we found that 78% of the anti-
inflammatory activity was present in
the supernatant. The wound healing
activity was present in the
precipitate with the polysaccharide
and other precipitated agents.
Nevertheless, in the supernatant
most of the anti- inflammatory
activity was present in the
supernatant without the presence of
the polysaccharide. Some of the
wound healing orchestra compounds
were precipitated with the
polysaccharide to help with the
wound healing activity. The
carrageenan-inflamed synovial pouch
response to Aloe vera confirms our
biological results based on the
Gowda experiment. The fibroblast
stimulation activity of Aloe vera
recorded in wound healing was
clearly observed. The fibroblast
response in the air pouch was not a
chronic inflammation but rather a
growth-repair response. Aloe
stimulates the fibroblast directly
to increase wound tensile strength.
It stimulates glucosamine to form
collagen and proteoglycan but zinc
and vitamin C must be present. Mast
cells of animals treated with
carrageenan were found in connective
tissue and pouch fluid. They were
particularly increased in the inner
being of the air pouch as a result
of the inflammation. Aloe vera
reduced the inflammation and the
pouch was vascularity but at the
same time Aloe vera increased the
pouch wall weight. This increase in
air pouch punch biopsy weight by
Aloe represents a healing and repair
response. Aloe stimulates directly
growth and repair by directly
stimulating fibroblasts. Aloe vera
has no anti-fibrosis effect but
stimulates the fibroblast for growth
and repair as seen in wound healing.
Both of these studies clearly
demonstrate that Aloe vera inhibits
inflammation and stimulates wound
healing at the same time which is
the miracle of Aloe. We have not
seen data to show that the magic
bullet (the polysaccharide) can do
this. In fact, this wonderful dual
biological characteristic appears to
be exclusive for Aloe vera.
The polysaccharide is an immune
stimulator which increases the
immune response to an antigen. La
Badie has shown that Aloe vera can
act as an adjuvant to enhance the
immune response to an antigen. He
found that there are two
functionally and chemically distinct
immunomodulatory compounds in the
gel of Aloe vera. One fraction could
enhance antibody formation and
another could inhibit antibody
formation such that La Badie called
Aloe vera an immune modulator. Davis
and La Badie showed that the Aloe
vera can inhibit and stimulate
phagocytosis as well as “mop up”
oxygen radicals. Aloe vera acts as
an immune stimulator on wound
healing and an immune inhibitor on
inflammation. Aloe vera can prevent
and regress the autoimmune condition
of adjuvant inducted arthritis. This
condition involves both antibody and
cellular immunity. Aloe vera can
inhibit the infiltration of
polymorphonuclear leukocytes into a
site of irritiation. This represents
a block on leukotrienes.
Under-nourished individuals have
impaired immune responses which may
be co- factors in the
immunodeficient virus infection.
This makes people more susceptible
to viral infection. The many
nutritional components in Aloe vera
may help the infected individual
fight off a disease as a co-factor
as well as play a role in regulating
the immune system (cell mediated
immunity). No single component such
as the polysaccharide can do the
complete job. A treatment of many
compounds as seen in Aloe vera would
seem to be more beneficial for a
multi- factorial syndrome. The
global AIDS problem may be out of
control because there is no
treatment. If the polysaccharide can
contribute in this area, possibly,
Aloe vera can even make a better
contribution because it is
multifaceted. Aloe vera has 200
biologically active agents as well
as polysaccharide to act as a
biological vehicle and a treatment
possibility.
Yagi presented data on the
isolation of a glycoprotein (Aloe
glycoprotein) which has
bradykinin-degrading activity and a
proteolytic activity against
bradykinin. The Aloe glycoprotein
has hemagglutinating and
cytoagglutinating activity. It has
mitogenic activity for lymphocytes.
This glycoprotein is called Aloctin
A. This glycoprotein has strong
anti-tumor activity whose activity
varies with the dose at microgram
amounts. Aloctin A is non toxic and
at very small doses causes complete
regression of tumors. Like the
polysaccharide, the glycoportein
appears to have an anti-tumor effect
based on cell division and immune
system response. Thus, the
polysaccharide is not the only magic
bullet, glycoprotein is another one.
In fact,
Aloe vera has many magic bullets
such as gibberellin, auxin, sterols
and chromones to mention a few.
All of these compounds are found
around the polysaccharide in the
orchestra.
The penetration of topical agents
through the skin may be influenced
by the drug, the vehicle and the
skin. Little attention has been
given to the influence of Aloe vera
and mucilage on the penetration
through the skin. The stratum
corneum acts as a barrier to drug
penetration through the skin but
also acts as a reservoir for
molecules when a drug is applied on
the skin. When hydrocortisone is
applied to the skin, 99% fails to
penetrate the skin stratum corneum
and is wasted. Placing
hydrocortisone in Aloe vera enhances
the penetration and adds to the
biological activity of
hydrocortisone. Aloe vera increases
the penetration of skin by water
hydration, occlusiveness and by
increasing compound solubil-ity.
Aloe vera increases the penetration
through the skin whereas the
polysaccharide mucilage acts as an
occlusive seal forming a firm cover
to keep moisture in the skin. Aloe
can aid water soluble and insoluble
compounds as a biological carrier so
that it can be a good carrier for
all kinds of drugs as well as
contributing Aloe activity to the
drug it carries. Can Aloe
polysaccharides alone aid in skin
penetration and add its biological
activity to an agent it carries? We
think it can not by itself. It needs
the orchestra environment of
biologically active compounds to
complete the task. The properties of
a large polysaccharide are
completely different from those of a
small polysaccharide. What is said
of the smaller one can not be
attributed to the larger one. In any
event, we need to see the data to
prove that the magic bullet - the
polysaccharaide - can act in a
fashion similar to Aloe vera. The
FDA must see the data recorded in
“commercial blurbs” backing up all
the claims made by people who say
“If you don’t have our
polysaccharide, you don’t have
active Aloe vera.”
This is not
true based on scientific evidence.
These claims are false and are made
by people motivated by money and not
by evidence.
Gibberellin is a growth factor
found in Aloe plants that has
anti-inflammatory and wound healing
activity in laboratory animals. It
does this in normal and diabetic
animals. Gibberellin’s wound healing
activity is related to its ability
to stimulate protein synthesis as
well as the RNA-DNA cellular systems.
It stimulates wound healing (open
and incisional wounds) in a
dose-response manner. Aloe vera and
gibberellin can stimulate
fibroblasts directly to form
collagen and proteoglycans for wound
healing. We also feel that Aloe vera
(or gibberellin) can stimulate or
modulate the macrophage to produce
the traditional growth factors which
stimulate fibroblasts. It appears
that Aloe vera or gibberellin can do
the same thing as proposed by the
polysaccharide. Because of the
contribution of other agents, they
probably do a better job on open and
incisional wounds. However, studies
need to be designed to show this.
Aloe vera and gibberellin are
anti-inflammatory even in the
diabetic. They improve wound
healing, reduce edema and pain. Aloe
vera has an additive “vehicle
effect” with gibberellin on wound
tensile strength. Gibberellin blocks
hydrocortisone’s inhibition on wound
healing similar to Aloe vera.
Hydrocortisone inhibits wound
healing by blocking the formation of
connective tissue. This increases
the spread of infection. Aloe vera
and gibberellin counteracts these
detrimental effects of steriods.
Gibberellin and Aloe vera block the
steriod inhibition on wound tensile
strength. Aloe vera contains three
sterols that have good
anti-inflammatory activity. They
exhibit anti-inflammation in a
dose-response fashion and may be a
major contributor to the
anti-inflammation in Aloe. Aloe vera
blocks a wide variety of irritants
that act by different biochemical
pathways. However, it has no chronic
anti-inflammatory activity because
it stimulates the fibroblast for
wound healing. However, we wonder if
it aids the hydrocortisone’s chronic
anti-inflammatory activity since
Aloe vera prevents and regresses
adjuvant induced arthritis. Aloe
vera acts as a biological vehicle
for aspirin and it synergizes with
its analgesic and anti- inflammatory
activity.
Summarizing the main effects of
Aloe vera, we must conclude that
gibberellin, sterols, chromones,
aspirin like compounds and auxins
are magic bullets in Aloe vera.
Mucilage improves wound healing,
glycoprotein is anabolic and
produces both anti-cancer effects
and immune system responses that are
anti-tumor. Both of these must be
considered magic bullets as well as
the polysaccharide found in the
parenchyma cells of the Aloe leaf.
Is it wise to precipitate the
polysaccharide with alcohol and
throw out all these wonderful
biological agents? Is it wise to say
that only the polysaccharide is
worthwhile when you are aware of
this data? I think not. It is
exceptable to isolate the various
compounds and evaluate them by
themselves. However, do not run down
Aloe vera from which they came. The
data presented here refutes the
concept that “If Aloe vera doesn’t
have a certain polysaccharide, its
not Aloe vera.” It rejects the
concept that only the polysaccharide
is active and important in Aloe
vera.
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