Aloe vera in wound healing: Gel components

2015

Saccharides

Mono- and polysaccharides form about 25% of the solid fraction of the aloe gel. Mannose and glucose are the most significant monosaccharides found in the gel. These sugars most commonly serve as fuels and building blocks. For example, mannose-6-phosphate is required to initiate glycoprotien and glycolipid synthesis in the endoplasmic reticulum of all nucleated cells. Optimal nutrition is required for the growth, regulation, reproduction, defense, regeneration and repair during wound healing. In addition, saccharides such as mannose are essential in the golgi apparatus of all cells to complete synthesis of all structural and functional molecules. Lastly, the mannose-6-phosphate of Aloe vera has been shown to activate the insulin-like growth factor receptor of the fibroblast, stimulating it to increase collagen and proteoglycan synthesis. This activity has been shown to increase wound tensile strength.

The polysaccharide component of aloe gel is primarily glucommannans that are comprised of glucose and mannose (β1→ 4 linked acetylated mannan). These polysaccharides, unlike other sugars, are absorbed complete and appear in the bloodstream undigested. Here, they have many activities. It has been very clearly indicated that the immunostimulant and wound-healing activities of Aloe vera gel reside, at least in part, in this glucomannan component, for after separation and purification, glucomannans retain immunostimulant, cell-proliferative, and anti-inflammatory activity. One of the most marked biological activities of mannans is the activation of macrophages and stimulation of T cells. In fact, macrophages are known to possess a specific receptor for mannans that is both on the cell surface and intracellularly, and as a result, mannans are potent immunostimulants with significant activity against infectious diseases.

In 1982, acemannan, aloe’s most common glucomannan, was successfully extracted and stabilized from Aloe vera gel. Acemannan has been well documented to enhance the immune system by stimulating the growth of macrophages, lymphocytes, NK (natural killer) cells, as well as the production of interferon and all known cytokines. Acemannan has been shown to induce interleukin-1 and prostaglandin E2 production by human peripheral blood cells and the exposure of lymphocytes to acemannan has been associated with an increase in antigen expression and NK cell activity. These properties have bestowed aloe with significant antimicrobial, anti-fungal and antiviral properties.

Sterols

These include campesterol, β-sitosterol and lupeol. These compounds are believed to have anti-inflammatory properties that aid in the coordination of local wound-healing activities.

Eicosanoids and terpenes

Eicosandoids and terpenes are active in connection with decreasing inflammation in wounds.

Gibberellin and auxin

The plant hormones gibberellin and auxin have shown an ability to inhibit inflammation and stimulate antibody production and wound healing in a dose-response manner.

Bradykininase

Aloe also contains a bradykininase, which is active in inhibiting inflammation in the wound bed. This enzyme is thought to be involved in the initial vasoconstriction seen with the topical application of the gel.

Inorganic electrolytes

Sodium, potassium, calcium, magnesium, manganese, copper, zinc, chromium and iron are all found in aloes. Magnesium lactate inhibits histidine decarboxylase, which prevents the formation of histidine. This may partially explain the antipuritic and anti-inflammatory effect of aloe. Also, the remaining electrolytes are essential parts of numerous enzymatic reactions that are important for cell growth, maintenance and wound healing.

Vitamins

Aloe is known to contain numerous vitamins that are vital for the maintenance of cell growth and cellular integrity. In addition, vitamins A, C and E are antioxidants that may be important in reducing inflammation in the wound. Vitamin C is needed in the cross-linking of collagen, which is required for normal wound tensile strength.

Anthraquinones

These phenolic compounds are found in the aloe sap (exudate) and are known to be potent antimicrobial and antiviral agents that possess powerful analgesic effects. Anthraquinones have also been shown to possess anti-inflammatory and anti-arthritic properties.

Saponins

Saponins comprise approximately 3% of aloe gel and are known to be cleansing agents with antiseptic properties.

Lignin

Lignin is an inert substance that endows aloe preparations with their singular penetrative ability to carry other active ingredients either deep into the skin in order to nourish the dermis or deep into the wound in order to aid in the healing process.

Amino acids

Amino acids are the building blocks of proteins, including enzymes and structural elements that are essential for cell growth and the wound-healing process. Aloe contains 20 of the 22 amino acids required by cells for protein synthesis, including seven of the eight essential amino acids that cannot be synthesized by the cell itself.

Mucilage

In 1963, Blitz et al. first suggested that aloe may expedite wound healing by serving as a protective barrier due to its occlusive properties. The occlusive cover-like qualities of the gel were later attributed to mucilage, which acts as a storage container inside the leaf. It also acts like a sealant or ‘bandage’ when a plant leaf is injured. It has been shown that dry wounds prevent the migration of cells and disrupt the effects of wound-healing growth factors. Aloe gel, acting as a cover, has been shown to keep the wound moist, allowing excellent migration of epidermal and fibroblast cells. In addition, the occlusive cover-like properties of mucilage allow it to serve as an organic bandage or dressing.

Antimicrobial properties

Even today we employ a varied armamentarium of topical substances to control and prevent infection, without a complete understanding of their influence on the process of wound healing. In fact, it has been demonstrated that concentrations of several antimicrobial agents used to control wound infections are in fact toxic to tissue-cultured cells. Extracts from Aloe vera gel have been shown to have beneficial heterogeneous properties, which include an ability to penetrate tissue, anesthetize tissue, preclude bacterial, fungal and viral growth, and dilate capillaries in order to enhance blood flow to injured tissue.

Infection plays a major role in influencing the rate of wound healing. In one study, when compared with other topical antimicrobials, the group treated with aloe gel healed significantly faster than the control group and had the shortest half-life overall. Topical aloe gel significantly enhanced the rate of wound healing and has also been shown to reverse the wound retardant effects of other topical agents.

Various studies have provided evidence that aloe retains antimicrobial effects against numerous organisms at concentrations of 60–70%.

In addition, as stated previously, the glucomannan component of Aloe vera gel possesses immunostimulant, antifungal and anti-viral activity. It has been shown to stimulate T cells and activate macrophages, causing an enhancement of the respiratory burst and phagocytosis. Acemannan has been shown to inhibit virus-induced cell fusion, reduce virus load and suppress the production and release of free virus from acutely infected cells. The ingestion of large mannan molecules has been shown to increase secretion of IL(interleukin)-1, interferon and TNF (tumor necrosis factor). As a result, aloe is a potent immunostimulant with significant activity against infectious disease. Its lack of significant toxicity, in combination with its macrophage-stimulating activity, makes aloe a prime candidate for further investigation as an immunostimulant in infectious disease and as an antitumor agent. In fact, acemannan has been used to treat retroviral infections and is currently being studied for its effects in combating the HIV virus.

Anti-inflammatory properties

At the time of tissue injury, the eicosanoid cascade is initiated by platelets and the primary mediator of progressive tissue loss is the potent vasoconstrictor, thromboxane A2. Aloe acts as a thromboxane A2 synthetase inhibitor, preventing its production and maintaining a balanced equilibrium between PGE2 and PGF2A. Aloe gel’s anti-thromboxane properties have been shown to dilate arteries and enhance local blood flow.

Aloe gel can block vasoactive substances responsible for inflammation, can constrict small blood vessels, can block PMN (polymorphonuclear leucocyte) infiltration, can inhibit the production of oxygen free radicals and can dilate capillaries allowing for increased blood supply to damaged tissue. These properties have given aloe the ability to reverse progressive tissue necrosis in partially damaged tissue. The plant hormones called gibberellins and auxins and the group of substances related to aspirin, known as the salicylates, seem to be the mediators of this response. In addition, there are organic compounds in aloe such as emolin, barbaloin and emodin that can be broken down by the Kolbe reaction into salicylates. The anti-thromboxane effect of these compounds may be due to enzymatic substrate competition. Aloe gel contains an abundance of fatty acids that allow for competitive inhibition of thromboxane production through stereochemical means, while also supplying the necessary nutrient precursors such as triglycerides and cholesterol for the initiation of the remaining arachidonic cascade. This allows for inhibition of inflammatory mediators while supplying the cell with the important constituents to maintain cellular integrity and normal tissue maturation.

Purified glucomannans have also shown impressive anti-inflammatory activity when separated from other aloe constituents. This concept has been supported by research in which the administration of mannans prevented arthritic flares in rats. Also, mannose inhibits free radical production by neutrophils, limiting tissue damage. This is important since the neutrophil is the hallmark cell of inflammation and its presence is crucial to the inflammatory response. Furthermore, polymannose can inhibit the initial step in the migration of neutrophils out of the blood stream and can aid in the clearance of certain pathogens through the presence of cell surface carbohydrate-receptor interactions.