By Robert H. Davis, Ph.D. 

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The Model For Aloe Vera  

The modern symphony orchestra combines instruments from strings, woodwinds, brass  and percussion to form an ensemble capable of beautiful musical expressions. Each of  these musical arrangements uniquely blends the sound of various instruments into one  given tone. As an orchestra tunes up, each instrument creates its own distinctive musical  notes. Out of this chaos comes the miracle of Mozart and the wonder of Beethoven.

One key element of the orchestra is the conductor. An outstanding conductor develops  an orchestra by a combining many aspects of musical training. His role is to understand  the potential contribution of each instrument and provide the leadership needed to create  a synergy of sounds. Although his position is important, the talented orchestra players are  the essential elements that must work together to produce the magic of a musical  symphony.

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How Aloe Vera Mimics The Orchestra 

     

“The Conductor-Orchestra concept” was  developed to better define the relationships that  exist among over 200 biologically active  compounds within Aloe vera (Figure 1). One of  these molecules, a polysaccharide, acts as the  conductor that leads a symphony composed of  these 200+ biologically active compounds. The  polysaccharide molecule consists of mannose  molecules joined by beta I-4 linkages to form a  chain. As the conductor, the polysaccharide  modulates the biological activity between  surrounding orchestra molecules to work  synergistically.

This conductor-orchestra relationship creates an infinite array of biological activities. The protein at one end of the polysaccharide helps  direct the mannose phosphate at the other end into the insulin-like growth factor receptor.  As part of the fibroblast, it produces collagen and proteoglycans to improve wound  healing. The Aloe vera molecule can also stimulate macrophages to produce a variety of  important biologically active substances. And it can recognize the receptors on other cell  surfaces as well as recognize the individual players within the orchestra. In addition, the  biological compounds indirectly help the conductor produce the biological response  occurring at the cell receptor. Altogether, the Aloe vera molecule leads an orchestra of  compounds working to produce a symphony of therapeutic effects. To suggest that the  conductor – the polysaccharide – works alone in this complex array of activity is  presumptive. Although there’s knowledge to gain from the isolation of biological  compounds and activities. It seems unwise to search for a “magic bullet.”

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What Is The Role Of Water In The Aloe Vera  Relationship  

The important question remains unanswered – How does the polysaccharide (the  conductor) communicate and relate to the 200 biologically active compounds in the  orchestra? Aloe is 99.5% water and 0.5% solids. The water is removed by tyophilization  but must be added again to recover the biological activities of Aloe vera. Water, although  a rather commonplace compound, is necessary for the activity of life. Water is not just a  solvent for organic molecules such as polysaccharides, but it plays a major role in the  relationship between the polysaccharide and the 200 active compounds in Aloe. The  interaction between the conductor and the orchestra arises from water’s polarity. The water molecules in Aloe vera have large oxygen atoms that draw electrons from two  hydrogen atoms, giving water a positive and negative charge at either end of the  molecule. This polarity enables water to dissolve active agents and to mold complex  molecules. The orchestra molecules as well as the conductor polysaccharide possess both  polar and non-polar parts. The polar parts react well with water whereas the non-polar or  hydrophobic parts avoid water. The polarity of water molecules aligns their negative ends  with the positive ends of other molecules. A chain of these polarized water molecules act  to connect the conductor polysaccharide with the orchestra molecules in Aloe vera. This  allows the conductor to communicate with the 200 orchestra compounds such as amino  acids, vitamins and sterols. Information is given to the conductor in a similar way to  influence the polysaccharides control over the orchestra.

The aloe plant is very water-dense, so it’s an ideal way to prevent or treat dehydration. Staying hydrated helps your body detox by providing a way for you to purge and flush out impurities. The juice also packs a hefty punch of nutrients that optimize your body’s organ output. ¹

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Standardization: The Aloe Vera Unit  

The conductor-orchestra theory has been adopted by key Aloe vera suppliers and new  manufacturing standards are being developed around this theory. A standardized “unit” of  Aloe vera should be established by the industry that samples a predetermined amount of  product for testing. This Aloe unit can then be tested and deliver a measurable biological chemical response. Other approaches to determine the activity of Aloe vera, such as  selectively testing only one, single component of this complex molecule, is unwarranted  and unscientific based on our current knowledge. Clearly, a “magic bullet” approach is  not valid. Science has proven that Aloe vera, in its natural composition, keeps the body in  a healthy physiological state. This does not mean that the study and fractionation of Aloe  vera is unimportant. Individual active components such as the polysaccharide may prove  very exciting for specific applications. However, the study of Aloe vera and its complete  compliment of components is necessary to fully understand the potential of Aloe vera.

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The Yin Yang Theory And Aloe  

The Yin Yang theory is used in eastern culture to indicate the active and passive  principles that bring balance to the universe. These two forces interact to bring all things  into existence. In a similar manner, Aloe vera moderates the balance of its own biological  systems. Aloe vera has an inhibitory system that blocks pain and inflammation as well as  a stimulatory system that improves growth and wound healing. Also, independent  laboratory testing of Aloe vera fractions has shown their activity to include modulation of  antibodies and cellular immunity. One example of the normalizing influence of Aloe vera  is its inhibition of the auto-immune condition demonstrated in adjuvant arthritis. Overall,  the beneficial effects of Aloe vera often result because two components act in such a way  (Yin Yang) to normalize the balance of activity.

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A Receptor For Aloe  Vera  

It has been well established that the  Insulin-like Growth Factor II (IGF II) and mannose-6-phosphate (M-6- P) bind to the same receptor on the

fibroblast (Figure 2). These two  ligands bind at separate binding  sites within the IGF-II/M-6-P  receptor. However, the exact effect  of these ligands binding to their  individual binding sites is still  unclear. One possible theory is that the binding of either ligand is capable of activating fibroblast proliferation. This would  indicate that free M-6-P is a growth substance capable of yielding the same response as  IGF-II. In Aloe, M-6-P is located at the end of the polysaccharide chain that fits into the

receptor. This may be important in understanding how Aloe heals wounds and inhibits  inflammation. It has been demonstrated that M-6-P improves wound healing in a straight  line, dose-response fashion when compared with controls. For example, Glucose-6- phosphate, when used as a control, does not activate the receptor in the fibroblast. The  binding site for this glucose is at the other end of the polysaccharide chain of Aloe and is  probably a weak to moderate covalent bond. Lack of response by this control indicates  that M-6-P is specific to the receptor. This may be important in understanding how Aloe  heals wounds and inhibits inflammation.

The receptor dynamics are part of the overall Aloe vera conductor-orchestra theory. One  exciting characteristic of this theory is that the conductor-orchestra unit has little or no  toxicity at very high gm/kg doses. Most of us working with Aloe vera have recorded no  toxicity. In fact, we feel that Aloe vera can modulate, reduce and may even eliminate  toxicity of other biological agents.

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Mechanism of  Action of Aloe  Vera: Wound  Healing 

The concept that the Aloe vera  molecule synergizes with plant  growth factors to repair and  produce growth, broadly  portrays the activity of Aloe  vera (Figure 3). Three

characteristics of growth factor  activity in Aloe are:

  1. Inhibition of pain &  inflammation  
  2. Stimulation of  fibroblasts to  functionally produce  collagen &  proteoglycans  
  3. Increased wound tensile strength  

The mechanism of Aloe’s inhibition of pain and inflammation will be detailed in  the next section, first we must understand how Aloe vera enhances wound  healing.

During the healing process, Aloe vera’s stimulation of the fibroblast produces  and adds new collagen to tissue. However, we should note that macrophages can  also secrete substances that can similarly stimulate fibroblasts. Whether the effect  is direct (from Aloe) or indirect (from microphages), new collagen forms between  the margins of wounds when Aloe is present. These collagen bonds are  responsible for increased tensile strength. Therefore, if the tensile strength  increases, it is assumed the collagen productions is increased by Aloe. This is a  different approach than the Danhof response of Aloe based on the uptake of  tritiated thymidine, which only represents an increase in fibroblasts number.  Whereas, we are demonstrating a functional increase in collagen and  proteoglycans through wound tensile strength.

When skin is injured, fibroblasts  migrate into the wound area to proliferate and produce collagen as well  as proteoglycans. Proteoglycans form the  ground substance in which collagen  fibers embed. This represents a  remodeling of connective tissue. Cells in  the wound area communicate with each  other by growth factors. Growth factors  in Aloe are attracted to the wound area  and bind to the fibroblast IGF receptor to  produce collagen and proteoglycans  which increase the tensile strength  (Figure 4).

Connective tissue is mainly composed of collagen, which makes up one third of our body protein. Also, connective  tissue contains large complex chains of modified sugars that form the framework  for collagen. These modified sugars hold water and give connective tissue  flexibility and resistance. In wound healing, collagen and proteoglycans repair  and remodel this connective tissue. To produce collagen for repair, glucose from  the diet is stimulated by Aloe vera and forms glucosamine within the fibroblast.  Then, in the presence of zinc and vitamin C, glucosamine forms procollagen. In  addition, procollagen can be formed directly from external amino acids. Next,  Aloe pushes the fibroblast to convert the secreted procollagen to collagen. The  glucosamine and procollagen form the “core protein” as a frame for connective  tissue. Also, they form hyaluronic acid as a frame for “link” proteins are essential  components for connective tissue. In addition, this connective tissue can double  and triple if the necessary sugars and amino acids are stimulated by Aloe vera in  the fibroblast.

This activity demonstrates how wound healing is enhanced when connective  tissue, subjected to mechanical forces and damages, repair themselves by the  Aloe-fibroblast stimulating influence to make collagen and proteoglycans. Aloe  vera acts as a mechanism to promote the active biological agents that heal  damaged tissue.

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Aloe Vera and Inflammation 

Inflammation is the response of living tissue to a damaging stimulus. It is a  defense mechanism against a traumatic insult. On a molecular basis, the  inflammatory process involves complex regulators, potentiators and mediators. A  uniform response occurs regardless of the nature of the irritant event, though the  inflammatory process may act as a double edge sword by also creating a threat to  an organism. Inflammation by be acute or chronic. The acute inflammation  response to a tissue insult involves the release of vasoactive substances. This  increases the permeability of capillaries so that fluid goes into interstitial tissue  and produces edema. Then, polymorphonuclear leukocytes (PMN’s) move out of  the capillaries and are attracted to the injury site by a mediator called leukotrienes.  The PMN’s increase their metabolism and oxygen consumption as they  phagocytize the trauma debris. However, the products resulting from this  increased metabolism contain oxygen radicals that attack the membrane lipids and  produce further inflammation. If the irritant remains under the skin, chronic  inflammatory response occurs. Connective tissue forms around the irritant and,  over a long period of time, attempts to push the trauma outside the body.  Lysozymes, products of these inflammatory cells, function in a manner to  modulate neutrophil (PMN) activity.

Topical steroids are usually applied to block acute and chronic inflammation but  their properties also retard wound healing. They decrease edema by reducing  capillary permeability, vasodilation and stabilizing lysosomal membranes.  Steroids can actually increase the spread of infection by inhibiting connective  tissue formation.

Aloe vera is also used to inhibit acute inflammation. But, unlike steroids, it  stimulates fibroblast growth to improve wound healing and block the spread of  infection. This is the miracle of Aloe.

Studies have shown that since only about 1% of steroids can penetrate the  stratum corneum of the skin, 99% is unavailable and wasted. Our data has shown  that Aloe vera can act as a vehicle for steroids – to improve absorption and act as  an efficient carrier. This is a significant economic consideration for Aloe vera.

The complexity of Aloe vera’s components makes the study of its anti inflammatory activity a difficult task. Aloe vera does not have a single  mechanism of action. Aloe vera contains amino acids such as phenylalanine and  tryptophane that have anti-inflammatory activity. The salicyclic acid in Aloe  prevents the biosynthesis of prostaglandins from arachidonic acid. This explains, in part, how Aloe reduces vasodilation and decreases the vascular effects of  histamine, serotonin and other mediators of inflammation. Since prostaglandins  play an integral role in regulating both inflammation and immune reactions, Aloe  vera can affect both of these systems by blocking prostaglandin synthesis. The  analgesic effect of Aloe vera is synergistic with aspirin. Since Aloe vera has both  stimulatory and inhibitory components. Aloe can modulate both immune and  inflammatory reactions. It can act as a stimulator of wound healing and antibody  production. Aloe can block prostaglandin and modulate the production of  lymphocytes and macrophage derived mediators (lymphokinins) including  interleukins and interferons.

Besides Aloe’s effects on inflammatory and immune reactions, it also acts as a  scavenger of free oxygen radicals produced by PMN’s. The vitamin C in Aloe  that inhibits inflammation picks up oxygen radicals to block the inflammatory  process. Vitamin E, a known antioxidant, is also a component of Aloe vera. These  biological effects of the orchestra work in collaboration with the conductor  (polysaccharide) to produce these valuable therapeutic effects.

Studies confirm that aloe vera juice has antiseptic, anti-inflammatory, and analgesic properties when applied topically. Applying to a burn or sunburn can alleviate pain and help the skin heal more quickly. Some people keep an aloe plant handy in the kitchen, a sort of living first aid kit. ²

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Aloe Vera Is a Biological Vehicle  

Compounds that are poorly absorbed through the stratum corneum of the skin  need a vehicle to aid them in penetration. Glucocorticoids and vitamin C are not  absorbed well and, as a result, most of the material is wasted when applied  topically. A vehicle must be found that solubilizes steroids and Vitamin C while  at the same time hydrates the stratum corneum. As previously mentioned. Aloe  vera’s anti-inflammatory, wound healing and analgesic properties make Aloe a  “biological vehicle” that helps to nullify the detrimental activity of  glucocorticoids but at the same time aids the penetration. Similarly, vitamin C is  not readily absorbed by the tissue. However, vitamin C has been shown to help in  the synthesis of collagen, since it may counterbalance the collagen breakdown to  reduce the development of autoantibodies. In certain diseases, such as rheumatoid  arthritis, the levels of vitamin C are low. Our data, thus far, suggests that Aloe  vera aids in the absorption of vitamin C and adds to its biological activity.  Although all the factors that control the absorption of vitamin C are not know,  previous studies show esterifying ascorbic acid increases the availability to tissues  so that the therapeutic dose can be reduced. In a similar manner, Aloe vera’s  activity as a biological vehicle to increase the absorption of vitamin C may be just  as possible.

Aloe vera can solubilize water soluble compounds as well as lipid soluble  substances. Also, it can hydrate the stratum corneum cell membranes to aid a  range of materials in penetrating the skin. The biological activity of Aloe can add  and even synergize with many agents in producing therapeutic effects so that we  call Aloe vera a “biological vehicle.”

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Summary  

Aloe vera contains polysaccharides that act as a conductor to direct biological  activities among an orchestra of various molecules. Many agents within Aloe  have been isolated, identified and demonstrated to synergize with one another over a large biological spectrum. A standard preparation of Aloe vera with a well defined unit for each biological activity is necessary for future research. The  conductor-orchestra theory opposes the idea that suggests that one molecule in  Aloe (a polysaccharide) is responsible for the beneficial effects and that the  standardization should be based on that polysaccharide. A greater understanding  between the conductor and orchestra is needed to better define how Aloe vera  synergizes its many activities. This understanding will change many  pharmacologic concepts in the future. The conductor-orchestra concept will be  practiced as the central format by which the Aloe industry will operate.

 

Dr. Robert Davis

Several years ago, Dr. Robert Davis of The University of Pennsylvania and a prominent Aloe expert, came to Dallas to share some astounding research. Dr. Davis found that Aloe Vera would increase wound healing by 121%. It did this by stimulating the fibro blast. Dr. Davis made this comment. “Aloe not only delivers nutrients to the body but it seems to have a zip code and knows where to deliver the nutrients.” (Remember that phrase: “Seems to have a zip code.”)

When people speak of an “active ingredient” in Aloe juice, they are usually referring to a group of long chain sugars formerly called Mucopolysaccharides and more recently referred to as Polysaccharides. While Polysaccharides undoubtedly have many amazing properties – they’ve been shown to be anti-inflammatory, anti-viral, immuno-stimulants, and more – they are just one portion of more than 200 Biologically Active Nutritional Components in Aloe. Davis developed a theory to explain the interaction between all these constituents. According to Davis, the Polysaccharide is the “Conductor” that modulates the activities of the “Orchestra”, the Vitamins, Minerals, Enzymes, Amino Acids, Growth Factors and other Nutritional Components. Dr. Davis stated, “Aloe Vera contains the greatest number of active substances of any plant I’ve looked at.”

Aloe Vera improves wound healing and inhibits inflammation. Davis, Robert H. (PhD), Di Donato, Joseph J. (BA, BS), Hartman, Glenn M. (BS), & Haas, Richard C. (BA). (1994, February). Anti-inflammatory and wound healing activity of a growth substance in Aloe Vera. Journal of the American Podiatric Medical Association, 84(2), 77-81. ³

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REFERENCES
  1. https://www.healthline.com/health/food-nutrition/aloe-vera-juice-benefits#benefits-of-aloe-vera-juice
  2. https://www.scientificamerican.com/article/what-are-the-benefits-of-drinking-aloe-juice/
  3. https://www.aloeveraaustralia.com.au/experts-practicality-to-the-power-of-aloe-vera/