© 2005 by Yampa Valley Botanical, LLC. All rights reserved. Electronic edition published 2005.
This site provides a comprehensive and balanced overview of scientific research on aloe. It is extensively referenced for those wishing to pursue further inquiries and study. It is not intended to provide medical advice or to substitute for the services of a qualified health care professional. Responsibility is specifically disclaimed for consequences incurred by those using the information reported.
Aloe vera (Aloe barbadensis Miller) is one of a number of herbal plant species that has been and continues to be extensively studied. The plant has many consistently identifiable active compounds. By and large, the studies presented in this botanical Library focus on one or more of such compounds.
The following bullet points summarize the effects attributable to compounds found in Aloe vera. They are listed in the same sequence as documented by the articles abstracted below.
• General history• Wound healingo Anti-inflammatoryo Antioxidanto Angiogenic (induces new blood vessels to form)• Immune system modulator• Tumor suppressive / cancer preventive• Anti-atherogenic (atherosclerosis preventive: lowers cholesterol and tryglycerides; raises HDL; may actually reverse coronary artery disease; may diminish dependency on a variety of drugs)o Anti-platelet adhesive (reduces platelet stickiness)o Anti-diabetico Antihypertensive (reduces or controls high blood pressure)o Antioxidant properties relating to anti-atherogenesis • Antibiotic / antiviral / antifungal / antiparasitic / • Promoter of chemical and drug detoxification of liver • Potential additional treatment for autoimmune gastrointestinal inflammatory diseases and duodenal and gastric ulcers• Manages psoriasis• Cathartic (fights constipation)• Stimulates hematopoiesis (blood cell formation)• Analgesic (relieves pain)• Spermicidal contraceptive----------------------------------------------------------• Agronomic information pertaining to variance of active constituents based upon geographical origin of aloe plants considered
Following are the active chemical compounds identified to date in Aloe vera in the abstracts following this narrative:
Aloesin (2-acetonyl-8-beta-d-glucopyranosyl-7-hydroxy-5-methylchromone) Anthraquinones, including aloin and aloe emodin Aloemannan, acemannan (gel polysaccharides) Aloeride Verectin, giberellin-like substance Aloeresin I; 5-methylchromone Flavonoids Glycoprotein fraction G1G1M1DI2 Anthraglycosides Reductive sugars Cardiotonic glycosides Saponins Carbohydrate naftoquinones Sterols Triterpenoids
NARRATIVE(Follows sequence of bullet points above and sequence of abstracts below)
Aloe vera gel has come to play a prominent role as a contemporary folk remedy and, over the years, many optimistic—in some cases extravagant—claims have been made for its medicinal properties. Modern clinical use of the gel began in the 1930s with reports of successful treatment of X-ray and radium burns, which led to further experimental studies using laboratory animals in the following decades. The reports of these experiments and the numerous favorable case histories did not provide much conclusive evidence since, while positive results were usually described, much of the work suffered from poor experimental design and insufficiently large test samples. In addition, some conflicting or inconsistent results were obtained. With the recent resurgence of interest in aloe, however, new experimental work has suggested the possibility of distinct physiological effects that are beneficial. The following abstracts of carefully designed studies have begun to credibly and conclusively clarify the many ways in which aloe works both to help maintain and to regain good health.
Much has been studied and written about the wound healing properties of Aloe vera. Injury occurs on many levels, and the response to injury is consistently seen on every level. The body’s responses are all too often overreactions that prolong healing. The following properties of aloe each contribute to accelerating a healing response to injury.
Anti-inflammatory Many of the abstracts below focus on how the compounds found in aloe work to prevent or stop inflammation caused by injury as well as inflammation caused byaging, immune dysfunction, autoimmune disease, cancer, and coronary artery disease.
Inflammation is a process that occurs both internally and externally in response to many types of trauma. The overt symptoms of inflammation are heat, redness, tenderness, swelling, and pain. Inflammation can be acute or chronic, mild or severe. It can also be almost imperceptible. The processes associated with inflammation take place on many different levels of biological organization at the same time. These range from the molecular or biochemical level up to and through levels of interaction of many systems in the body, to ultimately the expression of symptoms and signs present both subjectively and objectively. In the abstracts, many of these levels of organization are addressed in a scientific manner.
When a substance has been shown to have anti-inflammatory properties, that is to say it can stop or slow inflammation, it is very significant. For a variety of reasons, aloe gel is one such material that has this property.
Recently, it has been shown that very subtle changes of aging may have to dowith slow, silent types of chronic, yet barely perceptible, inflammation. This includes hardening of the arteries, which leads to many other degenerative conditions associated with aging. One of the abstracts reports that adding aloe to the diet of some 5,000 people with existing coronary artery disease significantly improved their overall coronary health.
One of the causes of inflammation and aging is the oxidation of substances that cause the formation of free radicals. A free radical is an atom or molecule that lacks an electron, which makes it unstable. To achieve completion, and therefore stability, the free radical captures an electron of another atom or molecule, which, in turn, causes the donor atom or molecule to itself become a free radical. This can result in a chain reaction that causes damage to cells, DNA, RNA, and certain enzymes, setting the stage for many diseases including cancer.
Cell metabolism normally produces free radicals, and the body produces several antioxidant enzymes. But free radicals are also caused by environmental factors, especially in today’s polluted world, such as heavy metals and chemicals in water and food. Aloe has been shown to be a strong antioxidant and scavenger of free radicals, thus protecting the body.
Angiogenic The term angiogenic means “encouraging or creating the formation of new blood vessels.” Wound healing requires new blood vessel formation. Aloe makes it happen. Aloe does this and more, including increasing the formation of fibroblasts, the cells that hold healing wounds together, thus increasing the tensile strength of the tissue. Some of the abstracts in the Library go into considerable detail in showing how these two properties of aloe work to the benefit of wound healing.
Immune System Modulator
Aloe works in a number of ways to enhance immune system functioning. The details of how this works is presented in many of the abstracts in the Library.
The immune system is almost as complex as the central nervous system. How the trillions of cells in our bodies work to protect us, and the signaling mechanisms used to communicate among all the different immune cell types that activate or deactivate certain chemical processes, is quite intricate To ascribe the term “immune modulator” or “adaptogen” to a substance is to ascribe to that substance a host of beneficial functions. Aloe is such a substance.
The basic function of the immune system is to discriminate between self and non-self entities. Things that are self belong in the body; things that are non-self do not. Examples of things that are self include the proteins making up specific parts of tissue like the thyroid gland, the large and small intestine, the lining of joints. Examples of non-self things include the sugar-protein complex of the coating of a virus, or the cell wall of a bacterium, or a blood cell introduced from another person.
The immune system, when functioning properly, reacts promptly to non-self in a variety of ways to rid the body of the invader. Sometimes in the course of living, the immune system becomes dysfunctional—becoming unable to distinguish between self and non-self—and begins mistakenly to reject things necessary as self.
This category of diseases is called autoimmune disease. Examples include rheumatoid arthritis, lupus erythematosis, polyarteritis nodosum, Hashimoto’s thyroiditis, scleroder-ma, ulcerative colitis, regional enteritis, and many more.
When we identify a substance we would call an immune modulator or adaptogen, we have truly found something very valuable indeed, because it helps the immune system to respond properly. It is truly a regulator of cellular and humoral immune function.
What is cellular and humoral immune function? The immune system has the ability to recognize, identify, and then remember the things that it encounters. Humoral refers to material that is dissolved in plasma, serum, or extracellular fluid spaces, which includes what the immune system cells produce in response to certain “invader” signals and then release into serum or plasma or the fluid surrounding cells of tissues and organs.
These substances, such as cytokines, chemokines, and serum complement, can be thought of as signals that create other effects, or they can be complex protein molecules called antibodies that attach themselves only to very specific targets for which they have been created. Then, once attached to the target, the antibody-target complex attracts other cells of the immune system, which come and destroy the target, releasing yet other molecules signaling other cells to come and clean up the debris. Examples of words connoting these signaling substances in solution include names like interferon, interleukins (abbreviated and numbered; e.g., IL-1, IL-6), and tumor necrosis factor (e.g., TNF-alpha). A number of the following abstracts discuss these substances.
The cells that respond to signals and do certain things to identify, recognize, remember, signal, destroy, and clean up are the cellular part of immune system function. There are many different types of cells we recognize by their individual functions. An example you will encounter is the T-helper cell, a type of lymphocyte. Another type of immune system cell is the polymorphonuclear leukocyte, an example of which is the neutrophil. You will see these words in the abstracts below concerning analyses of immune system function.
Tumor suppressive / cancer preventive
We need to find ways to prevent cancer and to treat it effectively once it occurs. Aloe does both.
Oxidation damages genes, which eventually can lead to cancer. These damaged segments of DNA are called adducts. When adducts become numerous in a single cell, they may create enough of a change in function to make that cell immortal, unrecognizable by the immune system, and very prone to rapidly and wildly create more cells just like it through mitosis, or cell division.
When the cell with altered genes first divides, it duplicates or copies all the errors the adducts contain into each of the two daughter cells. With each following division, each new cell, containing the same defects as the original cell, divides again and again. This is when cancer cells might be produced. So a substance that prevents free radicals from creating large quantities of adducts in cells is what we call cancer protective. Aloe does this.
A substance is tumor suppressive and cancer preventive when it has the ability to arrest the development of cancerous tumors without also affecting normal cellular development and reproduction.
With the exception of the nerve cells in the central nervous system, which are called neurons, all other cells in the body need to be replaced. That means the force and intelligence of life acting through the genes governs the rate and the specific identity of each cell that has to be reproduced to replace its aging and eventually dying neighbor, enabling organs and tissues to continue functioning the way they should.
When enough genetic damage occurs so that a cell loses the ability to reproduce itself accurately, the resulting progeny cells do not respond to all the various regulatory signals of the living body.
Such a cell becomes wild and separate from the rest of the cells in the organ or tissue, and as a result does not know when to stop dividing itself into new cells. It has become “immortalized” in that it now has its own identity and sustains itself like a thief stealing nourishment for its own existence.
This is a simplified explanation of what a cancer is. And further, a cancer may be so abnormal within the body as to render itself undetectable or unresponsive to the normal defenses of the immune system, which would normally immediately recognize and destroy it.
When a cancer becomes malignant, it essentially takes over the host and consumes it until the host dies, unless the cancer is therapeutically arrested. When the host dies, the cancer dies too, unless human intervention occurs before the host dies to isolate the cancer cells, nourish them, and let them grow in special environments called tissue culture media.
To help find remedies for cancer, experimental tissue cultures of actual cancers are valuable. When cultured, cancer cells can be studied to see what helps them survive and what hampers or kills them. We can also discover the mechanism by which agents that kill them work.
Some of the abstracts in the Library below explore examples of killing cancer cells in culture (in vitro). Using the knowledge gained in research, we might eventually be able to employ the methods that work in vitro for killing cancer in people. Compounds in aloe have been found to arrest cancer cells that normal chemotherapy has failed to work on.
Also, this technique has demonstrated that when aloe is combined with very small amounts of cancer-killing drugs, the combination works much better at stopping cancer cells than either aloe or drugs alone. This means potentially that by combining small amounts of chemotherapy drugs with aloe, less toxicity to the host will result from drugs that, when used alone, are marginally effective at differentiating normal cells from cancer cells.
The inability of cancer drugs to target only cancer cells is why some of them are so toxic to the person as a whole, even to the point where sometimes the treatment becomes as bad or worse than the disease itself. Chemotherapy has actually killed patients weakened by their cancer and the cumulative effects of aging to the extent that they cannot tolerate the toxic effects of the drugs. This underscores the importance of auxiliary and natural therapies that increase specificity of drugs targeting cancer cells, increase the body’s ability to detoxify drugs, support the function of normal cells, and lower the required amount of the drugs so that less toxic material remains in the body.
So when we describe a substance as tumor suppressive, we are saying that the substance slows or arrests the unregulated reproduction of cells. When we say a substance is cancer preventive, we are saying that a substance keeps the genetic damage from occurring such that unregulated cellular reproduction is suppressed. The abstracts in the Library report on studies showing that compounds of aloe are both cancer preventive and tumor suppressive, explaining in depth the mechanisms by which this remarkable herb does its job.
Anti-atherogenic (atherosclerosis preventive: lowers cholesterol and tryglycerides; raises HDL; may actually reverse coronary artery disease; may diminish dependency on a variety of drugs)
Preventing atherosclerosis or hardening of the arteries is one of the most significant health challenges of our time. It is now almost a given that a major consequence of aging is hardening of the arteries. Not only is this belief simply not true, there are a number of things we can do to both prevent and, in some cases, actually reverse atherosclerosis.
Aloe has been shown to benefit the circulatory system: Aloe lowers triglycerides and LDL cholesterol (“bad” cholesterol) and raises HDL cholesterol (“good” cholesterol). A number of studies demonstrated that with aloe added to the diet, symptoms and signs of coronary artery disease disappeared, and the participants did not progress to heart attacks. The same studies reported that patients were able to reduce or eliminate drugs taken for chest pain, blood pressure control, and blood sugar control.
In one study abstracted below, 5,000 people with documented coronary artery disease and angina pectoris (chest pain on exertion indicating lack of blood flow to the heart muscles) were fed differently, including a diet rich in Aloe vera. The results included (i) no more angina pectoris; (ii) no progression to lethal heart attacks; and (iii) no continuing dependence on pharmaceutical products previously needed to control symptoms (but which seemingly cured nothing). This study occurred in 1985 before any of what is presented here was known.
Hardening of the arteries is a complex process involving microscopic injuries to small and large arteries alike. When small arteries get too much hardened plaque, their diameter is made smaller causing the circulation of blood through them to be diminished. Consequently, the organs or tissues needing the blood is deprived, so that damage to them accrues because of a lack of oxygen and an inability to remove carbon dioxide and the toxic waste of cellular respiration.
In the case of the heart, when the coronary arteries are blocked with plaque (which consists of peroxidized lipids like cholesterol, triglycerides and similar fats, a calcium matrix, inflammatory cells, and other associated chemicals), blood sludges through rather than flows freely.
With exertion and when the heart muscle’s increased demand for oxygen goes unmet, heart muscle is injured and can even die. If a region of the heart cannot get blood when it needs it and the heart muscle dies, it is called a heart attack. If the wrong spot in the heart is attacked, the heart can stop, and the person dies immediately.
Anti-platelet adhesive (reduces platelet stickiness)
By reducing platelet stickiness, Aloe vera mitigates or prevents the acute coronary syndrome for which aspirin and Plavix® are currently used.
Another thing that happens to the blood with atherosclerosis and aging is that small particles called platelets, which are necessary for clotting to stop the bleeding when vessels are injured, become unusually sticky. If the blood in a small vessel slows too much because of plaque buildup, and platelets have become too sticky, a clot will form where it does not belong, often permanently damming off the flow of blood to the tissue that needs it.
Clotting is also what causes tissue damage in the brain (a stroke) and kidneys in people with hardening of the arteries and especially with diabetes, which accelerates the process of small vessel disease and the resulting damage to organs and tissues.
What is beautiful and amazing about the compounds individually, and especially collectively, in aloe is the ability to reduce platelet stickiness, decrease inflammation caused by microvascular injury, and reduce the buildup and generation of peroxidized lipids—in other words, maybe even reverse atherosclerosis as well as prevent it. Some of the abstracts in the Library deal with the proof of this statement, and it is definitely worth trying to read and understand.
Anti-diabetic By helping to control blood sugar, aloe lessens the damaging effects of type 2 diabetes; that is, accelerating hardening of the arteries and the blocking of small blood vessels.
Diabetes, which involves a loss of control over levels of blood glucose or blood sugar, causes microvascular damage and accelerates plaque deposition by stimulating the subtle inflammatory responses to injury we discussed above. Abstracts in the Library address how compounds in aloe are capable of lowering blood glucose levels in type 2 diabetes.
Antihypertensive (reduces or controls high blood pressure)
By reducing or controlling high blood pressure, aloe also diminishes the strain on the heart and keeps small arteries from narrowing. High blood pressure causes thickening of the walls of medium- and small-sized arteries, which in turn results in a narrowing of those vessels. This places further demand on the heart to pump against the resulting increased resistance. The narrowing also adds to the effects of plaque buildup.
Antioxidant properties relating to anti-atherogenesis
By preventing the oxidation of certain fats, aloe decreases the number of free radicals, which cause damage to the inside of arteries.
Antibiotic / antiviral / antifungal / antiparasitic
Evidence presented shows that there are natural antibacterial, antiviral, antifungal, and antiparasitic properties of Aloe vera. An abstract below demonstrates the killing of a sexually transmitted parasite called Trichomonas vaginalis. Studies in the “test tube” (in vitro) as well as studies in living organisms like chickens showed that aloe could arrest the reproduction of viruses that have a coat covering their genetic material. In fact, the only two viruses not stopped by aloe were adeno- and rhinoviruses (the cause of the common cold). More serious viral threats to human health such as those in the Herpes family were stopped. Potential use as a veterinary medicine was demonstrated in the study of a disease caused by a virus in chickens.
Promoter of chemical and drug detoxification of liver
The liver has many functions, too numerous to describe; but one is to chemically process drugs, environmental chemicals, and certain waste products of metabolism so that they are no longer toxic to the body. Evidence is presented in the Library that shows that the liver’s function can be enhanced by the action of some of the compounds in aloe. When combined with aloe’s antiviral, anti-inflammatory, and immune system modulating properties, the additional factor of enhancing liver processing of toxic wastes is a bonus.
Potential additional treatment for autoimmune gastrointestinal inflammatory diseases and duodenal and gastric ulcers
Because it is an immune system modulator, aloe has been found to be effective in preventing and treating certain autoimmune diseases such as ulcerative colitis and rheumatoid arthritis. Because chronic duodenal and gastric ulcers may be produced by a bacterial infection caused by Helicobacter pylori, and it has been shown that aloe kills that bacterium, aloe may serve to treat and prevent ulcers. It has also been shown to directly reduce acid secretion.
Even after drugs were discovered to reduce acid secretion, people with ulcers either would not heal or would only temporarily improve, only to have recurrent and progressively more serious episodes of ulceration with all the painful symptoms. Additionally, chronic gastritis and stomach ulcers over time lead to a predisposition for cancer of the stomach, just as an unremitting history of ulcerative colitis predisposes one to colon cancer.
So when we look at aloe, studies have shown that it reduces the inflammation associated with, and thereby brightens the clinical picture for, ulcerative colitis; it decreases stomach acid production, which protects the lining of a sensitive stomach prone to ulceration; and it kills the bacteria that predispose the stomach to chronic irritation and ulceration. Abstracts in the Library below elucidate the methods by which these discoveries were made.
May be considered a safe and effective treatment for psoriasis.
Cathartic (fights constipation)
One of the first uses for aloe was in relieving constipation.
Stimulates hematopoiesis (blood cell formation)
A number of studies suggest that some of aloe’s compounds stimulate new blood cell formation. Analgesic (relieves pain)
Analgesia is a property of aloe when applied topically and perhaps even when ingested to calm inflamed gastrointestinal tissues. An abstract in the Library sheds light on a mechanism that could explain this property, which is based on the neurophysiology of pain and the effect of aloe on this neurophysiology.
A single study is found in the literature showing that aloe is spermicidal and therefore could be adapted into a format to be used as a topical contraceptive for women.
Agronomic information pertaining to variance of active constituents based upon geographical origin of aloe plants considered
Variation in the active compounds has been documented based upon the geographical location of cultivars. The selection of high-yielding provenances, with total aloin levels above 25%, is recommended for commercial cultivation.
Editorial commentary and notes are in italics preceding, and also sometimes within, the abstracts.
A nice little history of aloe’s uses follows in this lead abstract.
J Ethnopharmacol. 1986 Jun;16(2-3):117-51. Related Articles, Links
The Aloe vera phenomenon: a review of the properties and modern uses of the leaf parenchyma gel.
Grindlay D, Reynolds T.
The mucilaginous gel from the parenchymatous cells in the leaf pulp of Aloe vera has been used since early times for a host of curative purposes. This gel should be distinguished clearly from the bitter yellow exudate originating from the bundle sheath cells, which is used for its purgative effects. Aloe vera gel has come to play a prominent role as a contemporary folk remedy, and numerous optimistic, and in some cases extravagant, claims have been made for its medicinal properties. Modern clinical use of the gel began in the 1930s, with reports of successful treatment of X-ray and radium burns, which led to further experimental studies using laboratory animals in the following decades. The reports of these experiments and the numerous favourable case histories did not give conclusive evidence, since although positive results were usually described, much of the work suffered from poor experimental design and insufficiently large test samples. In addition some conflicting or inconsistent results were obtained. With the recent resurgence of interest in Aloe vera gel, however, new experimental work has indicated the possibility of distinct physiological effects. Chemical analysis has shown the gel to contain various carbohydrate polymers, notably either glucomannans or pectic acid, along with a range of other organic and inorganic components. Although many physiological properties of the gel have been described, there is no certain correlation between these and the identified gel components.Although in 1986 the last sentence was for the most part true, what follows is a mountain of evidence to the contrary that accrues in an accelerating rate over a relatively short time!
Br J Gen Pract. 1999 Oct;49(447):823-8. Related Articles, Links
Aloe vera: a systematic review of its clinical effectiveness.
Vogler BK, Ernst E.
Department of Complementary Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter.
BACKGROUND: The use of aloe vera is being promoted for a large variety of conditions. Often general practitioners seem to know less than their patients about its alleged benefits. AIM: To define the clinical effectiveness of aloe vera, a popular herbal remedy in the United Kingdom. METHOD: Four independent literature searches were conducted in MEDLINE, EMBASE, Biosis, and the Cochrane Library. Only controlled clinical trials (on any indication) were included. There were no restrictions on the language of publication. All trials were read by both authors and data were extracted in a standardized, pre-defined manner. RESULTS: Ten studies were located. They suggest that oral administration of aloe vera might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia. Topical application of aloe vera is not an effective preventative for radiation-induced injuries. It might be effective for genital herpes and psoriasis. Whether it promotes wound healing is unclear. There are major caveats associated with all of these statements. CONCLUSION: Even though there are some promising results, clinical effectiveness of oral or topical aloe vera is not sufficiently defined at present.
Jump ahead in time and instead of the statements of our ignorance, the complexity and properties of many of the constituent compounds in aloe are compiled in the studies reported in the next abstract in 2003. Anti-inflammatory, antioxidant, and tumor suppressive properties are explored.
Yakugaku Zasshi. 2003 Jul;123(7):517-32. Related Articles, Links
[Anti-inflammatory constituents, aloesin and aloemannan in Aloe species and effects of tanshinon VI in Salvia miltiorrhiza on heart]
[Abstract in Japanese]
Yagi A, Takeo S.
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, 985 Gakuen-cho, Fukuyama 729-0292, Japan. email@example.com
Cinnamoyl, p-coumaroyl, feruloyl, caffeoyl aloesin, and related compounds were isolated from Aloe species. The antiinflammatory and antioxidative activities of these compounds were examined based on the structure-activity relationship. It was suggested that the bioactivities may link to acyl ester groups in aloesin, together with those of aloesin-related compounds. However, investigations using the contact hypersensitivity response indicated a preventive effect of aloesin on the UV-B-induced immune suppression. Furthermore, aloesin inhibited tyrosine hydroxylase and dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human melanocyte cell lysates. These results show that aloesin prevents not only UV-B-induced immune suppression, but also could be a positive pigment-altering agent for cosmetic application. In preclinical study, aloe extract was investigated using phagocytosis and nitroblue tetrazolium chloride (NBT) reduction in adult bronchial asthma, and high molecular-weight materials, such as polysaccharide and glycoprotein fractions, were identified as active ingredients. The neutral polysaccharides, aloemannan and acemannan showed antitumor, antiinflammatory and immunosuppressive activities, and glycoprotein fractions with bradykinin-degrading and cell proliferation-stimulating activities were identified from the nondialysate fraction of the gel part of Aloe species. Verectin fractionated from Aloe vera gel was examined biochemically and immunochemically, and verectin antibody was used in the appraisal of commercial Aloe vera gel products. It was reported that aloesin stimulates the proliferation of cultured human hepatoma SK-Hep 1 cells. Thus aloesin, related compounds, and high molecular-weight materials, such as aloemannan and verectin, may act in concert to exert therapeutic properties for wounds, burns and inflammation. The biodisposition [Editor’s note: where it went] of fluoresceinylisothiocyanate (FITC)--labeled aloemannan (FITC-AM) with the homogenate from some organs in mice was demonstrated, and FITC-AM was metabolized to a smaller molecule (MW 3000) by the large intestinal microflora in feces. The modified aloe polysaccharide (MW: 80000) with cellulase under restricted conditions, immunologically stimulated the recovery of UV-B-induced tissue in jury. Thus the modified polysaccharides of aloemannan, together with acemannan (MW: about 600000), are expected to participate in biological activity following oral administration. [Editor’s note: abstract truncated at this point due to its continuation with compounds from another herbal medicinal plant)]This next fairly recent abstract generally sets the stage for what is to come. J Ethnopharmacol. 1999 Dec 15;68(1-3):3-37. Related Articles, Links
Aloe vera leaf gel: a review update.
Reynolds T, Dweck AC.
Jodrell Laboratory, Royal Botanic Gardens, Kew, Richmond, Surrey, UK.
Research since the 1986 review has largely upheld the therapeutic claims made in the earlier papers and indeed extended them into other areas. Treatment of inflammation is still the key effect for most types of healing but it is now realized that this is a complex process and that many of its constituent processes may be addressed in different ways by different gel components. A common theme running through much recent research is the immunomodulatory properties of the gel polysaccharides, especially the acetylated mannans from Aloe vera, which are now a proprietary substance covered by many patents. There have also been, however, persistent reports of active glycoprotein fractions from both Aloe vera and Aloe arborescens. There are also cautionary investigations warning of possible allergic effects on some patients. Reports also describe antidiabetic, anticancer and antibiotic activities, so we may expect to see a widening use of aloe gel. Several reputable suppliers produce a stabilized aloe gel for use as itself or in formulations and there may be moves towards isolating and eventually providing verified active ingredients in dosable quantities.Wound healingWound healing is a real focus of medicinal applications of aloe. There are many types of wounds and many models used to study and evaluate the effect of aloe on the wound healing process. We have included many abstracts covering this broad topic.Anti-inflammatory propertiesMore history using aloe preparations topically to treat skin inflammation; possible mechanisms explored in this, the first abstract focusing on inflammation in an experimental model of arthritis:J Am Podiatr Med Assoc. 1989 Jan;79(1):24-6. Related Articles, Links
Aloe vera and gibberellin. Anti-inflammatory activity in diabetes.
Davis RH, Maro NP.
Aloe vera inhibits inflammation and adjuvant-induced arthritis [Editor’s note: This type of arthritis is an experimental model. A chemical from a class of chemicals called adjuvants provokes joint inflammation. The authors' laboratory has shown that A. vera improves wound healing, which suggests that it does not act like an adrenal steroid.] Diabetic animals were used in this study because of their poor wound healing and reduced anti-inflammatory capabilities. The anti-inflammatory activity of A. vera and gibberellin was measured in streptozotocin-induced diabetic mice by measuring the inhibition of polymorphonuclear leukocyte infiltration into a site of gelatin-induced inflammation over a dose range of 2 to 100 mg/kg. Both Aloe and gibberellin similarly inhibited inflammation in a dose-response manner. These data tend to suggest that gibberellin or a gibberellin-like substance is an active anti-inflammatory component in A. vera.A similar study follows, corroborating the above study.J Am Podiatr Med Assoc. 1989 Jun;79(6):263-76. Related Articles, Links
Anti-inflammatory activity of Aloe vera against a spectrum of irritants.
Davis RH, Leitner MG, Russo JM, Byrne ME.
The authors have evaluated the spectrum of anti-inflammatory activity of A. vera in a number of models of inflammation in the hind paw of the experimental rat induced by kaolin, carrageenan, albumin, dextran, gelatin, and mustard. Croton oil was used in a topical model of inflammation to determine the oral activity and time-dependent dosing of A. vera. The authors found that A. vera was active in all models of inflammation. Of the various irritants tested, A. vera was especially active against gelatin-induced and kaolin-induced edema and, in contrast, had minimal activity when tested against dextran-induced edema. Oral activity of A. vera was demonstrated to be dependent on the presence of anthraquinones. The various irritant-induced edema models provided a broad spectrum of anti-inflammatory activity for A. vera.More on anti-inflammatory efficacy:J Am Podiatr Med Assoc. 1989 Aug;79(8):395-7. Related Articles, Links
Processed Aloe vera administered topically inhibits inflammation.
Davis RH, Rosenthal KY, Cesario LR, Rouw GA.
Aloe vera preparations were evaluated for topical anti-inflammatory activity using the croton oil-induced edema assay. The results show that small amounts of A. vera given topically will inhibit inflammation induced by a moderate amount of irritant. In general, the decolorized Aloe was more effective than the colorized Aloe (with anthraquinone). A 47.1% inhibition of inflammation was obtained by 5% decolorized irradiated Aloe. These results may be used as a baseline to assess the biologic activity of A. vera in the treatment of inflammation by podiatric physicians.The main point of the following abstract is “Aloe vera appears to act as a modulatory system toward wounds and inflammation and is a potentially valuable tool for managing lower extremity conditions.”J Am Podiatr Med Assoc. 1991 Sep;81(9):473-8. Related Articles, Links
Isolation of a stimulatory system in an Aloe extract.
Davis RH, Parker WL, Samson RT, Murdoch DP.
Pennsylvania College of Podiatric Medicine, Philadelphia 19107.
The authors' previous work on a 50% ethanol extract of Aloe vera was done to evaluate anti-inflammatory activity using the croton oil-induced ear swelling assay. The anti-inflammatory activity was found in the supernatant fraction. The supernatant fraction decreased inflammation, when applied topically, by 29.2%, and the precipitate decreased inflammation by 12.1%. However, in the present work, the precipitate fraction decreased the wound diameter by an average of 47.1% (stimulatory system). Little or no wound healing activity was found in the supernatant. Aloe vera appears to act as a modulatory system toward wounds and inflammation and is a potentially valuable tool for managing lower extremity conditions.And:J Am Podiatr Med Assoc. 1994 Feb;84(2):77-81. Related Articles, Links
Anti-inflammatory and wound healing activity of a growth substance in Aloe vera.
Davis RH, Donato JJ, Hartman GM, Haas RC.
Department of Biomedical Sciences, Pennsylvania College of Podiatric Medicine, Philadelphia.
Aloe vera improves wound healing and inhibits inflammation. Since mannose-6-phosphate is the major sugar in the Aloe gel, the authors examined the possibility of its being an active growth substance. Mice receiving 300 mg/kg of mannose-6-phosphate had improved wound healing over saline controls. This dose also had anti-inflammatory activity. The function of mannose-6-phosphate in A. vera is discussed.Along similar lines, Aloe vera has anti-inflammatory properties and the capacity to increase wound tensile strength, promoting healing and overcoming the negative impact of cortisone, which lowers tensile strength as it decreases inflammation.J Am Podiatr Med Assoc. 1994 Dec;84(12):614-21. Related Articles, Links
Aloe vera, hydrocortisone, and sterol influence on wound tensile strength and anti-inflammation.
Davis RH, DiDonato JJ, Johnson RW, Stewart CB.
Pennsylvania College of Podiatric Medicine, Philadelphia.
Aloe vera at doses of 100 and 300 mg/kg daily for 4 days blocked the wound healing suppression of hydrocortisone acetate up to 100% using the wound tensile strength assay. This response was because of the growth factors present in A. vera masking the wound healing inhibitors such as sterols and certain amino acids. The sterols showed good anti-inflammatory activity (-36%) in reducing the croton oil-induced ear swelling. This activity displayed a dose-response relationship.
The next abstract illustrates a mechanism with an experimental model. Aloe stimulates proven healing by stimulating growth of fibroblasts and macrophages (the cells involved in healing inflamed joints.
J Am Podiatr Med Assoc. 1992 Mar;82(3):140-8. Related Articles, Links
Aloe vera and the inflamed synovial pouch model.
Davis RH, Stewart GJ, Bregman PJ.
Pennsylvania College of Podiatric Medicine, Philadelphia.
Administration of air under the skin produced a pouch wall that closely resembled a synovium (joint lining) in that the inner lining was made up of macrophages and fibroblasts. Administration of 1% carrageenan directly into the 7-day-old air pouch produced an inflammation characterized by an increased number of mast cells in pouch fluid as well as an increase in wall vascularity. (Editor’s note: This model represents the lining in a joint called a synovial space, as in a knee joint, which when inflamed is called synovitis) A punch biopsy weight of the pouch wall did not reveal an increase in 1% carrageenan-treated animals. However, a 10% Aloe vera treatment of carrageenan-inflamed synovial pouches reduced the vascularity 50% and the number of mast cells in synovial fluid 48%. The pouch wall punch biopsy weight was increased by A. vera, which was verified by histologic examination of the inner synovial lining. Aloe vera stimulated the synovial-like membrane, as evidenced by an increased number of fibroblasts, suggesting that A. vera stimulated fibroblasts for growth and repair of the synovial model. The synovial air pouch can be used to study simultaneously the acute anti-inflammatory and fibroblast stimulating activities of A. vera.The preceding study shows how aloe stimulated the growth of fibroblasts in a model of a joint, lending insight into the mechanism of how aloe increases tensile strength in wound healing reported in the abstract above this one.
More anti-inflammatory data is found in the following abstract.
Planta Med. 2005 Jan;71(1):79-81. Related Articles, Links
Aloeresin I, an anti-inflammatory 5-methylchromone from cape aloe.
Speranza G, Morelli CF, Tubaro A, Altinier G, Duri L, Manitto P.
Dipartimento di Chimica Organica e Industriale, Universita degli Studi di Milano, Italy.
A new diglucoside having a 5-methylchromone moiety was isolated from a commercial sample of Cape aloe, the dried exudate from Aloe ferox Miller, and named aloeresin I. Its structure was established as 1 on the basis of spectral and chemical evidence. Aloeresin I ( 1) (1 mumol/cm (2)) reduces in vivo the oedematous response (39 %) induced by Croton oil in the mouse ear with the same potency as aloesin, one of the most abundant Cape aloe constituents, and to a higher extent than aloeresin H ( 2). Indomethacin [Editor’s note: indomethacin is a potent nonsteroidal anti-inflammatory drug with significant risk of toxicity to liver and GI hemorrhage] (0.3 mumol/cm (2)), the reference anti-inflammatory compound, provokes 61 % oedema inhibition.Aloeresin was 2/3 as effective as the drug used for a standard.To determine more about how aloe promotes wound healing, read the next study.Br J Dermatol. 2001 Oct;145(4):535-45. Related Articles, Links
The wound-healing effect of a glycoprotein fraction isolated from aloe vera.
Choi SW, Son BW, Son YS, Park YI, Lee SK, Chung MH.
Department of Pharmacology, Seoul National University College of Medicine, Seoul 110-799, Korea.
BACKGROUND: Aloe vera has been used as a family medicine for promoting wound healing, but it is not known which component of the plant is effective for this purpose. OBJECTIVES: To isolate and characterize the component effective in wound healing. METHODS: Chromatography, electrophoresis and spectroscopic methods were used. The cell-proliferation activity of each component isolated was measured by a [3H]thymidine uptake assay. The cell-proliferation activity of the effective component was tested on a three-dimensional raft culture (cell culture technique by which artificial epidermis is made from keratinocytes). The effect of the active component on cell migration and wound healing was observed on a monolayer of human keratinocytes and in hairless mice. RESULTS: A glycoprotein fraction was isolated and named G1G1M1DI2. It showed a single band on sodium dodecyl sulphate-polyacrylamide gel electrophoresis, with an apparent molecular weight of about 5.5 kDa. It exhibited significant [3H]thymidine uptake in squamous cell carcinoma cells. The effect of G1G1M1DI2 on cell migration was confirmed by accelerated wound healing on a monolayer of human keratinocytes. When this fraction was tested on a raft culture, it stimulated the formation of epidermal tissue. Furthermore, proliferation markers (epidermal growth factor receptor, fibronectin receptor, fibronectin, keratin 5/14 and keratin 1/10) were markedly expressed at the immunohistochemical level. The glycoprotein fraction enhanced wound healing in hairless mice by day 8 after injury, with significant cell proliferation. CONCLUSIONS: It is considered that this glycoprotein fraction is involved in the wound-healing effect of aloe vera via cell proliferation and migration.In frostbite, along with other modalities, aloe helps prevent tissue loss.Postgrad Med. 1990 Dec;88(8):67-8, 73-7. Related Articles, Links
Frostbite. Methods to minimize tissue loss.
McCauley RL, Heggers JP, Robson MC.
Department of Surgery, University of Texas Medical School, Galveston.
If frostbite is to be treated successfully, direct and indirect effects of injury must be understood. Rapid rewarming helps to preserve tissue by limiting the amount of direct cellular injury. Selective management of blisters helps protect the subdermal plexus, and application of Aloe vera cream (e.g., Dermaide Aloe Cream) combats the local vasoconstrictive effects of thromboxane. Oral administration of ibuprofen decreases systemic levels of thromboxane.Another abstract regarding aloe’s efficacy in the treatment of frostbite.Arch Otolaryngol Head Neck Surg. 1995 Jun;121(6):678-80. Related Articles, Links
Treatment of experimental frostbite with pentoxifylline and aloe vera cream.
Miller MB, Koltai PJ.
Division of Otolaryngology, Albany (NY) Medical College, USA.
OBJECTIVE: To compare the therapeutic effects of systemic pentoxifylline and topical aloe vera cream in the treatment of frostbite. DESIGN: The frostbitten ears of 10 New Zealand white rabbits were assigned to one of four treatment groups: untreated controls, those treated with aloe vera cream, those treated with pentoxifylline, and those treated with aloe vera cream and pentoxifylline. MAIN OUTCOME MEASURES: Tissue survival was calculated as the percent of total frostbite area that remained after 2 weeks. RESULTS: The control group had a 6% tissue survival. Tissue survival was notably improved with pentoxifylline (20%), better with aloe vera cream (24%), and the best with the combination therapy (30%). CONCLUSION: Pentoxifylline is as effective as aloe vera cream in improving tissue survival after frostbite injury.Frostbite treatment efficacy of aloe follows in a protocol in combination with other substances. This next abstract shows the synergy achieved, with emphasis on the thromboxane inhibitors, of which aloe is one of two.Ann Emerg Med. 1987 Sep;16(9):1056-62. Related Articles, Links
Experimental and clinical observations on frostbite.
Heggers JP, Robson MC, Manavalen K, Weingarten MD, Carethers JM, Boertman JA, Smith DJ Jr, Sachs RJ.
Experimental ischemia by the classic frostbite rabbit ear model clearly defined the role of thromboxane as a mediator of progressive dermal ischemia in frostbite injuries. The therapeutic groups consisted of the antiprostanoids, methylprednisolone, and aspirin combined with anti-thromboxane agents Aloe vera and methimazole, while the control group received no therapy. Survival was measured by planimetry for all groups. No tissue survival was evident in the frostbite control group. Methimazole treatment allowed 34.3% survival, Aloe vera 28.2% survival, aspirin 22.5% survival, and methylprednisolone 17.5% survival. The data compare the results of a modified frostbite protocol using ibuprofen with therapeutic modalities used by other clinical services. Of 154 patients treated for frostbite from 1982 to 1985, 56 were treated with our frostbite protocol; 98 were treated with other modalities. Of the 56 protocol patients, 18 suffered 1st degree frostbite, 25, 2nd degree frostbite, and 13, 3rd degree frostbite. For all degrees of frostbite, 67.9% healed without tissue loss, 25.0% healed with partial tissue loss, and 7% required amputation (P less than .001). Of the patients not on protocol, 11 suffered 1st degree frostbite, 51, 2nd degree frostbite, and 36, 3rd degree frostbite. Of these, 32.7% healed without tissue loss, 34.6% healed with tissue loss, and 32.7% required amputation. The morbidity of progressive dermal ischemia in frostbite may be decreased by the therapeutic use of inhibitors of the arachidonic acid cascade.Read the numbers above several times to get the full impact of what happens when the protocol of patients incorporating aloe are compared with the controls. The conclusions are understated. The next abstract illustrates another situation in which thromboxane is the major factor in inducing tissue damage and shows once more the synergy when aloe and methimizole, both thromboxane inhibitors, are combined.J Hand Surg [Am]. 1987 Mar;12(2):240-5. Related Articles, Links
The role of thromboxane in experimental inadvertent intra-arterial drug injections.
Zachary LS, Smith DJ Jr, Heggers JP, Robson MC, Boertman JA, Niu XT, Schileru RE, Sacks RJ.
Inadvertent intra-arterial injection of drugs produces a well-defined clinical syndrome whose pathophysiology remains unclear. This study was designed to determine the role of the inflammatory mediator, thromboxane, in intra-arterial drug injections. The rabbit ear model, as described by Kinmonth and Sheppard, was used.[Editor’s note: this is the same model as for studying frostbite] Five of the experimental groups were treated with specific or nonspecific thromboxane blocking agents and two groups served as controls. Immunohistochemical staining of the control ears showed elevated levels of thromboxane within the first 6 hours postinjury. The specific thromboxane blocking agents, methimazole and Aloe vera, showed almost complete blockade of thromboxane production. The percentage of ear survival was significantly greater in the group treated with topical Aloe vera (p less than 0.05) and even greater survival was achieved in the combined Aloe vera/methimazole group (p less than 0.01). On the basis of these results, we have begun treatment of such injuries with specific and nonspecific thromboxane blocking agents.A contrasting view of aloe as a topical anti-inflammatory and promoter of healing, the next study shows that the value of the gel was lower than the aqueous cream in healing the destructive effects of radiation therapy for breast cancer on the associated skin.Cancer Nurs. 2002 Dec;25(6):442-51. Related Articles, Links
A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue.
Heggie S, Bryant GP, Tripcony L, Keller J, Rose P, Glendenning M, Heath J.
Queensland Radium Institute, Division of Oncology, Royal Brisbane Hospital, Australia. Pauline_Rose@health.qld.gov.au
The aim of the study was to see if topical aloe vera gel would be beneficial in reducing the identified skin side-effects of radiation therapy, including erythema, pain, itching, dry desquamation, and moist desquamation, when compared with aqueous cream. The secondary aim was to assess the effect of other factors known to predict severity of radiation skin reaction, i.e., breast size, smoking habit, and one or more drainages of lymphocele after surgery, on other skin side effects. A Phase III study was conducted involving 225 patients with breast cancer after lumpectomy or partial mastectomy, who required a course of radiation therapy using tangential fields. Patients were randomized to either topical aloe vera gel or topical aqueous cream to be applied 3 times per day throughout and for 2 weeks after completion of radiation treatment. Weekly skin assessments were performed by nursing staff. Aqueous cream was significantly better than aloe vera gel in reducing dry desquamation and pain related to treatment. Subjects with D cup or larger size breasts experienced significantly more erythema, regardless of treatment arm. For subjects who had undergone lymphocele drainage, the aloe vera group experienced significantly more pain than the aqueous cream group. Within the aqueous cream arm, smokers were significantly more likely to experience itching within the treatment field than were nonsmokers. Within the aloe vera arm, subjects who had undergone one or more lymphocele drainages after surgery were significantly more likely to experience erythema and itching within the treatment field than those who did not have drainage. In this study, aloe vera gel did not significantly reduce radiation-induced skin side effects. Aqueous cream was useful in reducing dry desquamation and pain related to radiation therapy.Another abstract demonstrating lack of efficacy of aloe on radiation-induced skin damage:Int J Radiat Oncol Biol Phys. 1996 Sep 1;36(2):345-9. Related Articles, Links
Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity.
Williams MS, Burk M, Loprinzi CL, Hill M, Schomberg PJ, Nearhood K, O'Fallon JR, Laurie JA, Shanahan TG, Moore RL, Urias RE, Kuske RR, Engel RE, Eggleston WD.
Toledo Community Clinical Oncology Program, OH, USA.
PURPOSE: Considerable pilot data and clinical experience suggested that an aloe vera gel might help to prevent radiation therapy-induced dermatitis. METHODS AND MATERIALS: Two Phase III randomized trials were conducted. The first one was double blinded, utilized a placebo gel, and involved 194 women receiving breast or chest wall irradiation. The second trial randomized 108 such patients to aloe vera gel vs. no treatment. Skin dermatitis was scored weekly during both trials both by patients and by health care providers. RESULTS: Skin dermatitis scores were virtually identical on both treatment arms during both of the trials. The only toxicity from the gel was rare contact dermatitis. CONCLUSIONS: This dose and schedule of an aloe vera gel does not protect against radiation therapy-induced dermatitis.Another study of Aloe vera and mucosal damage from radiation therapy again presents a situation in which the type of skin or, in this case, mucosal damage induced by radiation is not benefited by Aloe vera gel:Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):171-7. Related Articles, Links
Phase II double-blind randomized study comparing oral aloe vera versus placebo to prevent radiation-related mucositis in patients with head-and-neck neoplasms.
Su CK, Mehta V, Ravikumar L, Shah R, Pinto H, Halpern J, Koong A, Goffinet D, Le QT.
Department of Radiation Oncology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5302, USA.
PURPOSE: In a single-institution, double-blind, prospective, randomized trial, we determined whether oral aloe vera gel can reduce radiation-induced mucositis in head-and-neck cancer patients. METHODS AND MATERIALS: We randomized 58 head-and-neck cancer patients between oral aloe vera and placebo. To be included in this Phase II protocol, patients had to be treated with radiotherapy with curative intent at Stanford University between February 1999 and March 2002. We examined patients biweekly for mucositis at 15 head-and-neck subsites and administered quality-of-life questionnaires. RESULTS: Patients in the aloe and placebo groups were statistically identical in baseline characteristics. By the end of treatment, the two groups were also statistically identical in maximal grade of toxicity, duration of Grade 2 or worse mucositis, quality-of-life scores, percentage of weight loss, use of pain medications, hydration requirement, oral infections, and prolonged radiation breaks. CONCLUSION: In our randomized study, oral aloe vera was not a beneficial adjunct to head-and-neck radiotherapy. The mean quality-of-life scores were greater in the aloe vera group, but the differences were not statistically significant. Oral aloe vera did not improve tolerance to head-and-neck radiotherapy, decrease mucositis, reduce soreness, or otherwise improve patient well-being.Here is a contrasting view of a specific type of wound healing in which it appeared that chemically aloe prolonged wound healing in women who underwent C-section delivery.Obstet Gynecol. 1991 Jul;78(1):115-7. Related Articles, Links
Aloe vera dermal wound gel is associated with a delay in wound healing.
Schmidt JM, Greenspoon JS.
Department of Nursing, Women's Hospital, Los Angeles County-University of Southern California Medical Center.
We evaluated the time interval required for wound healing using a standard wound management protocol with and without aloe vera gel. Twenty-one women were studied who had wound complications requiring healing by second intention after cesarean delivery or laparotomy for gynecologic surgery. Wounds treated with standard management healed in a mean (+/- SD) time interval of 53 +/- 24 days, whereas those treated with aloe vera gel required 83 +/- 28 days (P = .003). The use of aloe vera dermal wound gel was associated with a significant delay in wound healing compared with treatment with an otherwise identical regimen that did not include aloe vera.Note that in the above study, and perhaps in other studies, hormonal influences (such as those encountered after the stress of radiation injury) were not isolated as variables that could have influenced aloe’s efficacy. Aloe does better with burns and frostbite than it does with radiation.J Med Assoc Thai. 1995 Aug;78(8):403-9. Related Articles, Links
Effect of aloe vera gel to healing of burn wound a clinical and histologic study.
Visuthikosol V, Chowchuen B, Sukwanarat Y, Sriurairatana S, Boonpucknavig V.
Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
In a study of twenty-seven patients with partial thickness burn wound, they were treated with aloe vera gel compared with vaseline gauze. It revealed the aloe vera gel treated lesion healed faster than the vaseline gauze area. The average time of healing in the aloe gel area was 11.89 days and 18.19 days for the vaseline gauze treated wound. Statistical analysis by using t-test and the value of P < p =" 0.015)" p =" 0.015)." href="mailto:firstname.lastname@example.org">email@example.com
Antioxidant components in Aloe vera were examined for lipid peroxidation using rat liver microsomal and mitochondrial enzymes. Among the aloesin derivatives examined, isorabaichromone showed a potent antioxidative activity. The DPPH radical and superoxide anion scavenging activities were determined. As one of the most potent components, isorabaichromone together with feruloylaloesin and p-coumaroylaloesin showed potent DPPH radical and superoxide anion scavenging activities. Electron spin resonance (ESR) using the spin trapping method suggested that the potent superoxide anion scavenging activity of isorabaichromone may have been due to its caffeoyl group. As A. vera has long been used to promote wound healing, the inhibitory effects of aloesin derivatives for cyclooxygenase (Cox)-2 and thromboxane (Tx) A 2 synthase were examined and the participation of p-coumaroyl and feruloyl ester groups in the aloesin skeleton was demonstrated. These findings may explain, at least in part, the wound healing effects of A. vera. Abbreviations. ADP: adenosine diphosphate ASA: ascorbic acid BHT: butylated hydroxytoluene BSA: bovine serum albumin DMPO:5,5-dimethyl-1-pyrroline N-oxide DPPH:1,1-diphenyl-2-picrylhydrazyl EDTA: eidetic acid HEPES: N-(2-hydroxyethyl)-piperazine- N-2'-ethane-sulfonic acid NADH: reduced nicotinamide adenine dinucleotide NADPH: reduced nicotinamide adenine dinucleotide phosphate NBT: nitroblue tetrazolium Pg: prostaglandin SOD: Superoxide dismutase TBA: thiobarbituric acid TCA: trichloroacetic acid XOD: xanthine oxidaseMore on antioxidant properties and potency of aloe related to the age of the plant at harvest:J Agric Food Chem. 2003 Dec 17;51(26):7788-91. Related Articles, Links
Evaluation of antioxidant potential of aloe vera (Aloe barbadensis miller) extracts.
Hu Y, Xu J, Hu Q.
College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, PRC.
The polysaccharide and flavonoid concentrations of two-, three-, and four-year-old Aloe vera were determined, and their antioxidant activities were evaluated compared to BHT and alpha-tocopherol by the DPPH radical scavenging method and the linoleic acid system at 100 microg of soluble solids per mL of ethanol. The results showed that three-year-old Aloe vera contained significantly higher levels of polysaccharides and flavonoids than two- and four-year-old Aloe vera, and no significant differences in flavonoid levels were found between three- and four-year-old Aloe vera. All the aloe extracts showed significant antioxidant activity. The antioxidant activity of Aloe vera extracts and reference compounds followed the order: three-year-old Aloe vera > BHT > four-year-old Aloe vera > alpha-tocopherol > two-year-old Aloe vera. The three-year-old extract exhibited the strongest radical scavenging activity of 72.19%, which is significantly higher than that of BHT at 70.52% and alpha-tocopherol at 65.20%. These data suggest that the growth stage plays a vital role in the composition and antioxidant activity of Aloe vera.Angiogenic propertiesAnother positive factor regarding aloe’s promoting wound healing relates to this study demonstrating that aloe gel promotes new blood vessel formation.Angiogenesis. 1999;3(2):117-23. Related Articles, Links
A novel angiogenic factor derived from Aloe vera gel: beta-sitosterol, a plant sterol.
Moon EJ, Lee YM, Lee OH, Lee MJ, Lee SK, Chung MH, Park YI, Sung CK, Choi JS, Kim KW.
Department of Molecular Biology, Pusan National University, Pusan, Korea.
Aloe vera gel has a beneficial effect on wound healing. Because angiogenesis is an essential process in wound healing, we hypothesized that Aloe vera gel might contain potent angiogenic compounds. Here we demonstrate that Aloe vera gel and its extracts are angiogenic on the chorioallantoic membrane (CAM) of chick embryo. Out of the three compounds purified from the final fraction of Aloe vera gel, beta-sitosterol showed a potent angiogenic activity in the CAM assay. In the presence of heparin, beta-sitosterol stimulated neovascularization in the mouse Matrigel plug assay and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay. Thus beta-sitosterol is a novel plant-derived angiogenic factor which may have potential pharmaceutical applications for the management of chronic wounds.Immune system modulatorThe history of immunopharmacology gives insight into the mechanism of anti-inflammatory activity and immune modulation of Aloe vera gel.Note: Serum complement represents a series of numbered molecules that are signaling devices used in immunologically active inflammatory processes leading to antibody responses against specific antigens. The study below focuses on C-3.Planta Med. 1989 Dec;55(6):509-12. Related Articles, Links
An anti-complementary polysaccharide with immunological adjuvant activity from the leaf parenchyma gel of Aloe vera.
t'Hart LA, van den Berg AJ, Kuis L, van Dijk H, Labadie RP.
The aim of the study is to develop new substances with immunomodulatory activity. To this end, extracts from plants used in traditional medicine are used as starting material. This study deals with the mucilagenous leaf-gel of Aloe vera which is well reputed for its therapeutical effect on inflammatory-based disorders. The purification of an aqueous gel-extract guided by inhibition of complement activity in HPS is described. Using anion-exchange and gel permeation chromatography a highly active polysaccharide fraction was isolated, that is present in the gel in various chain lengths. The polysaccharides consist of several monosaccharides of which mannose is dominant. The inhibition is based on alternative pathway activation, resulting in consumption of C3. With respect to their biological activity the polysaccharides inhibit the opsonization of zymosan in HPS and display adjuvant activity on specific antibody production and the induction of delayed type hypersensitivity in mice. The immunological effects of acemannan, one of many active compounds in aloe, may explain aloe’s antiviral capabilities observed more recently and focused on later in the Library.Int J Immunopharmacol. 1988;10(8):967-74. Related Articles, Links
Enhancement of allo-responsiveness of human lymphocytes by acemannan (Carrisyn).
Womble D, Helderman JH.
Renal Immunology Laboratory, University of Texas Southwestern Medical Center, Dallas.
Healing powers have been imputed as being a feature of the gel from the aloe vera plant for centuries. The recent isolation of the active ingredient, acemannan, has made testing of this drug important. Since the drug appears to enhance monocyte function in other experiments, these studies were designed to test the capacity of acemannan to enhance immune response to alloantigen (foreign) and to test whether the potential enhancement is a monocyte driven phenomenon. Acemannan did not enhance lymphocyte response to syngeneic (self) antigens in the mixed lymphocyte culture (MLC) but importantly increased alloantigenic response in a dose-response fashion (2.6 x 10(-7) - 2.6 x 10(-9)M). This effect of acemannan was shown to be a specific response and to concur with concentrations of in vitro acemannan achievable in vivo. A separate series of mixing experiments demonstrated that acemannan incubation with monocytes permitted monocyte driven signals to enhance T-cell response to lectin. It is concluded that acemannan, the active ingredient of the aloe vera plant, is an important immunoenhancer in that it increases lymphocyte response to alloantigen. It is suggested that the mechanism involves enhancement of monocyte release of IL-I under the aegis of alloantigen. This mechanism may explain in part the recently observed capacity of acemannan to abrogate viral infections in animal and man.
The next abstract describes a recent discovery of a new immunologically active compound within aloe juice contributing to its immunomodulatory properties.J Agric Food Chem. 2001 Feb;49(2):1030-4. Related Articles, Links
Characterization of Aloeride, a new high-molecular-weight polysaccharide from Aloe vera with potent immunostimulatory activity.
Pugh N, Ross SA, ElSohly MA, Pasco DS.
Department of Pharmacognosy, National Center for Natural Products Research, University of Mississippi, University, Mississippi 38677, USA.
We have characterized a new immunostimulatory polysaccharide called Aloeride from commercial aloe vera (Aloe barbadensis) juice. Aloeride is between 4 and 7 million Da [Editor’s note: Da is an abbreviation for Dalton, which is a unit of molecular weight], and its glycosyl components include glucose (37.2%), galactose (23.9%), mannose (19.5%), and arabinose (10.3%). At 0.5 microg/mL Aloeride increased NF-kappa B directed luciferase expression in THP-1 human monocytic cells to levels 50% of those achieved by maximal concentrations (10 microg/mL) of LPS (lipopolysacharrides). Aloeride induced the expression of the mRNAs encoding IL-1beta and TNF-alpha to levels equal to those observed in cells maximally activated by LPS. Acemannan, the major carbohydrate component from aloe, used at 200 microg/mL in the macrophage assay resulted in negligible NF-kappa B activation. Analysis of acemannan and Aloeride using size-exclusion chromatography suggests that the low activity of acemannan is due to trace amounts of Aloeride. Although Aloeride comprises only 0.015% of the aloe juice dry weight, its potency for macrophage activation accounts fully for the activity of the crude juice.Tumor suppressive / cancer preventive
A comparative study of the anticancer and cancer chemo-preventive properties of several medicinal plants, leading with Aloe vera, follows. The term “DNA adduct formation” means that the structure/function of a segment of DNA on which specific genes are located has been damaged by oxidation. The damaged segment is called an adduct. When the genes are damaged, cancer can be a likely outcome.
Carcinogenesis. 1999 Aug;20(8):1637-40. Related Articles, Links
In vitro chemopreventive effects of plant polysaccharides (Aloe barbadensis miller, Lentinus edodes, Ganoderma lucidum and Coriolus versicolor).
Kim HS, Kacew S, Lee BM.
Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Changan-ku, Chunchun-dong, Kyunggi-do, Suwon 440-746, Korea.
A plant polysaccharide, Aloe gel extract, was reported to have an inhibitory effect on benzo[a]pyrene (B[a]P)-DNA adduct formation in vitro and in vivo. Hence, chemopreventive effects of plant polysaccharides [Aloe barbadensis Miller (APS), Lentinus edodes (LPS), Ganoderma lucidum (GPS) and Coriolus versicolor (CPS)] were compared using in vitro short-term screening methods associated with both initiation and promotion processes in carcinogenesis. In B[a]P-DNA adduct formation, APS (ALOE PLANT POLYSACCHARIDES) (180 micrograms/ml) was the most effective in inhibition of B[a]P binding to DNA in mouse liver cells. Oxidative DNA damage (by 8-hydroxydeoxyguanosine) was significantly decreased by APS (180 micrograms/ml) and CPS (180 micrograms/ml). In induction of glutathione S-transferase activity, GPS was found to be the most effective among plant polysaccharides. In screening anti-tumor promoting effects, APS (180 micrograms/ml) significantly inhibited phorbol myristic acetate (PMA)-induced ornithine decarboxylase activity in Balb/3T3 cells. In addition, APS significantly inhibited PMA-induced tyrosine kinase activity in human leukemic cells. APS and CPS significantly inhibited superoxide anion formation. These results suggest that some plant polysaccharides produced both anti-genotoxic and anti-tumor promoting activities in in vitro models and, therefore, might be considered as potential agents for cancer chemoprevention.The next abstract states: “These results suggest that Aloe vera gel contains at least two small molecular weight immunomodulators that may prevent UVB-induced immune suppression in the skin.”
Based upon the following, it is conceivable that the inhibition by aloe of the production of melanin and proliferation of melanocytes noted in the next study may suggest a preventive influence over the development of melanoma, a skin malignancy directly related to overexposure to UV sun irradiation.
Immunopharmacology. 1997 Oct;37(2-3):153-62. Related Articles, Links
Prevention of ultraviolet radiation-induced suppression of accessory cell function of Langerhans cells by Aloe vera gel components.
Lee CK, Han SS, Mo YK, Kim RS, Chung MH, Park YI, Lee SK, Kim YS.
College of Pharmacy, Chungbuk National University, Cheongju, South Korea.
The active components of Aloe vera gel that can prevent ultraviolet B (UVB)-induced suppression of accessory cell function of Langerhans cells (LC) were purified by activity-guided sequential fractionation [Editor’s note: These cells referred to as LC are intrinsic to the epidermis and are affected by UV radiation, as in sunburn. It is important to note the relationship between overexposure of skin to sunlight and the incidence and prevalence of a variety of skin cancers.] followed by in vitro functional assay. The functional assay was based on the fact that exposure of freshly isolated murine (MOUSE) epidermal cells (EC) to UVB radiation resulted in impairment of accessory cell function of LC, as measured by their ability to support anti-CD3 monoclonal antibody (mAb)-primed T-cell mitogenesis. [Editor’s note: The above is a description of the model the researchers created of a specific cell type induced to malfunction immunologically.] This UVB-suppressed LC accessory cell function was prevented by addition of partially purified aloe gel components to cultures of UVB-irradiated EC. The aloe gel components appeared to prevent events occurring within the first 24 h after UVB irradiation that lead to the impairment of accessory cell function. The aloe gel components did not cause proliferation of anti-CD3 mAb-primed T-cells, nor did [they] induce proliferation of normal EC. The activity-guided final purification of aloe gel components resulted in the isolation of two components. Both of the components were small molecular weight (MW) substances with an apparent MW of less than 1,000 Da but different from each other in net charge characteristics at pH 7.4. These results suggest that Aloe vera gel contains at least two small molecular weight immunomodulators that may prevent UVB-induced immune suppression in the skin.One other cancer-preventive mechanism for aloesin, another potential application for aloe, emerges which appears to support a mechanism for preventing UV stimulation of melanocyte transformation to melanoma.
Pigment Cell Res. 2002 Oct;15(5):335-40. Related Articles, Links
Modulation of melanogenesis by aloesin: a competitive inhibitor of tyrosinase.
Jones K, Hughes J, Hong M, Jia Q, Orndorff S.
Univera Pharmaceuticals Inc., Broomfield, CO 80021, USA. firstname.lastname@example.org
Aloesin, [2-acetonyl-8-beta-d-glucopyranosyl-7-hydroxy-5-methylchromone], a compound isolated from the Aloe plant, is shown in these studies to modulate melanogenesis via competitive inhibition of tyrosinase. Aloesin inhibits purified tyrosinase enzyme and specifically inhibits melanin production in vitro. Enzyme kinetics studies using normal human melanocyte cell lysates and cell-based melanin production demonstrated that aloesin is a competitive inhibitor of tyrosinase from mushroom, human and murine sources. Tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (DOPA) oxidase activities of tyrosinase from normal human melanocyte cell lysates were inhibited by aloesin in a dose dependent manner. In a percutaneous absorption study a finite dose of aloesin penetrated the skin slowly and was recovered primarily in the surface wash. Aloesin shows promise as a pigmentation-altering agent for cosmetic or therapeutic applications.
Antitumor effects from Aloe vera have been studied and noted:
J Pharm Pharmacol. 2000 May;52(5):593-8. Related Articles, Links
Anti-leukaemic and anti-mutagenic effects of di(2-ethylhexyl)phthalate isolated from Aloe vera Linne.
Lee KH, Kim JH, Lim DS, Kim CH.
Animal Resource Research Center, Konkuk University, Seoul, Korea.
Extracts of Aloe vera Linne have been found to exhibit cytotoxicity against human tumour cell lines. This study examines the anti-tumour effects of di(2-ethylhexyl)phthalate (DEHP) isolated from Aloe vera Linne, in human and animal cell lines. Its anti-mutagenic effects were examined using Salmonella typhimurium TA98 and TA100 strains. Growth inhibition was specifically exerted by DEHP against three leukaemic cell lines at concentrations below 100 microg mL(-1). At 100 microg mL(-1) DEHP, K562, HL60 and U937 leukaemic cell lines showed growth inhibition of 95, 97 and 95%, respectively. DEHP exhibited an inhibitory activity of 74, 83 and 81%, respectively, in K562, HL60 and U937 cell lines at a concentration of 10 microg mL(-1). At a concentration of 1 microg mL(-1), DEHP exerted an inhibitory activity of 50, 51 and 52%, respectively, in K562, HL60 and U937. In a normal cell line, MDBK, DEHP exerted 30% growth inhibition at a concentration of 100 microg mL(-1), and showed no inhibitory activity at concentrations below 50 microg mL(-1). It was found that DEHP exerted anti-mutagenic activity in the Salmonella mutation assay. The number of mutant colonies of Salmonella typhimurium strain TA98 upon exposure to AF-2 (0.2 microg/plate) decreased in a concentration-dependent manner in the presence of different DEHP concentrations (decreasing to 90.4, 83.9, 75.4, 69.6 and 46.9%, respectively, for DEHP concentrations of 100, 50, 10, 5 and 1 microg/plate). In the case of Salmonella typhimurium strain TA100, DEHP reduced AF-2-induced mutagenicity at 1, 5, 10, 50 and 100 microg/plate to 57.4, 77.5, 80.0, 89.0 and 91.5%, respectively. The isolated compound from Aloe vera Linne, DEHP, was considered to be the active principle responsible for anti-leukemic and anti-mutagenic effects in-vitro.Some of the same research group amplify:
J Pharm Pharmacol. 2000 Aug;52(8):1037-41. Related Articles, Links
Induction of apoptosis in human leukaemic cell lines K562, HL60 and U937 by diethylhexylphthalate isolated from Aloe vera Linne.
Lee KH, Hong HS, Lee CH, Kim CH.
Animal Resource Research Center, Konkuk University, Seoul, Korea.
We investigated the effect of diethylhexylphthalate (DEHP) from Aloe vera Linne on the apoptosis of human leukaemic cell lines K562, HL60 and U937 to examine its pharmacological activity. At a level of 10 microg mL(-1) DEHP a significant anti-leukemic effect was observed for all three cell lines, as measured by clonogenic assay. After treatment with 10 microg mL(-1) DEHP for 4 h, agarose gel electrophoresis and flow cytometric analysis confirmed the occurrence of apoptosis. These results indicate that DEHP isolated from Aloe vera Linne has a potent antileukemic effect, and thus represents a new type of pharmacological activity with respect to human leukemic cells.
A variety of possible anticancer mechanisms attributable to aloe:
Food Chem Toxicol. 2004 Aug;42(8):1251-7. Related Articles, Links
Aloe-emodin induced in vitro G2/M arrest of cell cycle in human promyelocytic leukemia HL-60 cells.
Chen HC, Hsieh WT, Chang WC, Chung JG.
Department of Pharmcology, China Medical University, 91 Hsueh-Shih Road, Taichung 404, Taiwan, ROC.
In this study, we have evaluated the chemopreventive role of aloe-emodin in human promyelocytic leukemia HL-60 cells in vitro by studying the regulation of proliferation, cell cycle and apoptosis [Editor’s note: apoptosis = programmed cell death]. Aloe-emodin inhibited cell proliferation and induced G2/M arrest and apoptosis in HL-60 cells. Investigation of the levels of cyclins B1, E and A by immunoblot analysis showed that cyclin E level was unaffected, whereas cyclin B1 and A levels increased with aloe-emodin in HL-60 cells. Investigation of the levels of cyclin-dependent kinases, Cdk1 and 2, showed increased levels of Cdk1 but the levels of Cdk2 were not effected with aloe-emodin in HL-60 cells. The levels of p27 were increased after HL-60 cells were cotreated with various concentrations of aloe-emodin. The increase of the levels of p27 may be the major factor for aloe-emodin to cause G2/M arrest in these examined cells. Flow cytometric assays and DNA fragmentation gel electrophoresis also confirmed aloe-emodin induced apoptosis in HL-60 cells. The levels of caspase-3 were increased after HL-60 cells were cotreated with 10 microM aloe-emodin for 12, 24, 48, and 72 hours. Taken together, aloe-emodin therefore appears to exert its anticarcinogenesis properties by inhibiting proliferation and inducing cell cycle arrest and apoptosis underwent activation of caspase-3 in human leukemia HL-60 cells.Aloe emodin is an effective anticancer agent in another specific type of cancer:Cancer Res. 2000 Jun 1;60(11):2800-4. Related Articles, Links
Aloe-emodin is a new type of anticancer agent with selective activity against neuroectodermal tumors.
Pecere T, Gazzola MV, Mucignat C, Parolin C, Vecchia FD, Cavaggioni A, Basso G, Diaspro A, Salvato B, Carli M, Palu G.
Department of Histology, Microbiology, and Medical Biotechnologies, Medical School, University of Padova, Italy.
Here we report that aloe-emodin (AE), a hydroxyanthraquinone present in Aloe vera leaves, has a specific in vitro and in vivo antineuroectodermal tumor activity. [Editor’s note: in vivo means in living organisms while in vitro means in some type of extracorporeal experimental situation, as “in a test tube.”] The growth of human neuroectodermal tumors is inhibited in mice with severe combined immunodeficiency without any appreciable toxic effects on the animals. The compound does not inhibit the proliferation of normal fibroblasts nor that of hemopoietic progenitor cells. The cytotoxicity mechanism consists of the induction of apoptosis, whereas the selectivity against neuroectodermal tumor cells is founded on a specific energy-dependent pathway of drug incorporation. Taking into account its unique cytotoxicity profile and mode of action, AE might represent a conceptually new lead antitumor drug.
Another recent and similar study on Merkel cell carcinoma cells shows aloe-emodin’s efficacy in fighting cancer:
Am J Dermatopathol. 2002 Feb;24(1):17-22. Related Articles, Links
The effect of aloe emodin on the proliferation of a new merkel carcinoma cell line.
Wasserman L, Avigad S, Beery E, Nordenberg J, Fenig E.
Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Rabin Medical Center Beilinson Campus, Petah Tikva 49100, Israel. email@example.com
A free-floating cell line has been established from a metastatic lesion of a Merkel cell carcinoma (MCC) patient. [Editor’s note: This means that these cells were grown from an actual patient’s cancer in cell culture conditions, so that in theory what happens to these cells in culture should happen to the tumor cells in the patient.] The cell line was characterized by immunocytochemical reactions with antibodies against the epithelial and neuroendocrine antigens: cytokeratin 20, neuron-specific enolase, chromogranin A, neurofilament protein, synaptophysin, and calcitonin. Karyotype analysis of the MCC cells showed deletion in chromosomes 3 and 7, loss of chromosome 10, and several translocations in other chromosomes. No mutation was detected in the TP53 gene, after analyzing the complete coding region. Growth factors such as basic fibroblast growth factor, transforming growth factor-beta, and nerve and epidermal growth factors had no effect on the proliferation of the cells. The differentiation-inducing agents sodium butyrate and dimethyl sulfoxide, especially the former, markedly inhibited the proliferation of the MCC cells. Aloe emodin, a natural constituent of aloe vera leaves, significantly inhibited the growth of MCC cells. Aloe emodin has been reported to be nontoxic for normal cells but to possess specific toxicity for neuroectodermal tumor cells. Differentiation-inducing agents, and aloe emodin, merit further investigation as potential agents for treating MCC.Merkel cell carcinoma (MCC), discussed above, which is resistant to most forms of chemotherapeutic intervention, may benefit from aloe-emodin plus low concentrations of other potent anticancer drugs.
Oncol Rep. 2004 Jan;11(1):213-7. Related Articles, Links
Combined effect of aloe-emodin and chemotherapeutic agents on the proliferation of an adherent variant cell line of Merkel cell carcinoma.
Fenig E, Nordenberg J, Beery E, Sulkes J, Wasserman L.
Institute of Oncology, Rabin Medical Center, Beilinson Campus, Petah Tiqva 49100, Israel. firstname.lastname@example.org
Merkel cell carcinoma (MCC) has only limited sensitivity to chemotherapeutic agents. The aim of the study was to determine if members of the anthraquinone family could be used as adjuncts to increase the growth inhibiting effect of anticancer agents in MCC. An adherent variant of MCC was derived from a previously established MCC cell line suspension. Cells were characterized by immunocytochemical methods using specific antibodies against epithelial (low molecular weight cytokeratins and cytokeratin 20) and neuroendocrine (neuron-specific enolase, neurofilament protein, chromogranin A and synaptophysin) antigens. Emodin and aloe-emodin, members of the anthraquinone family, inhibited proliferation of the adherent MCC cells, with a slight advantage of aloe-emodin over emodin. Aloin had no effect on cell proliferation. The chemotherapeutic agents, cis-platinol (abiplastin), doxorubicin (adriablastin), and 5-fluorouracil, and the tyrosine kinase inhibitor STI 571, all independently inhibited the proliferation of adherent MCC cells. The addition of aloe-emodin potentiated their inhibitory effect, especially when low concentrations of the anticancer compounds were used. [Editor’s note: The value of this finding suggests that by adding in the benefit of the anthraquinones of aloe emodin, one can use lower concentrations of toxic anticancer drugs and get even better results against the cancer than obtainable with the toxic drugs by themselves.] The antiproliferative action of STI 571 may be associated with the presence of anti-c-kit antibodies. The combined use of anticancer agents, especially at low concentrations, and aloe-emodin may be considered a preferable means for treating MCC.Two genetic mechanisms operate through aloe-emodin-induced arrest of cancer cell proliferation in two different liver cancer cell lines and are potentially protective of liver cells becoming cancerous.
Life Sci. 2002 Sep 6;71(16):1879-92. Related Articles, Links
The antiproliferative activity of aloe-emodin is through p53-dependent and p21-dependent apoptotic pathway in human hepatoma cell lines.
Kuo PL, Lin TC, Lin CC.
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
The aim of this study is to investigate the anticancer effect of aloe-emodin in two human liver cancer cell lines, Hep G2 and Hep 3B. We observed that aloe-emodin inhibited cell proliferation and induced apoptosis in both examined cell lines, but with different antiproliferative mechanisms. In Hep G2 cells, aloe-emodin induced p53 expression and was accompanied by induction of p21 expression that was associated with a cell cycle arrest in G1 phase. In addition, aloe-emodin had a marked increase in Fas/APO1 receptor and Bax expression. In contrast, with p53-deficient Hep 3B cells, the inhibition of cell proliferation of aloe-emodin was mediated through a p21-dependent manner that did not cause cell cycle arrest or increase the level of Fas/APO1 receptor, but rather promoted aloe-emodin induced apoptosis by enhancing expression of Bax. These findings suggest that aloe-emodin may be useful in liver cancer prevention.More on antitumor potential of aloe:
Int Immunopharmacol. 2001 Jul;1(7):1275-84. Related Articles, Links
Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells.
Lee JK, Lee MK, Yun YP, Kim Y, Kim JS, Kim YS, Kim K, Han SS, Lee CK.
College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
Acemannan, a major carbohydrate fraction of Aloe vera gel, has been known to have antiviral and antitumoral activities in vivo through activation of immune responses. The present study was set out to define the immunomodulatory activity of acemannan on dendritic cells (DCs), which are the most important accessory cells for the initiation of primary immune responses. Immature DCs were generated from mouse bone marrow (BM) cells by culturing in a medium supplemented with GM-CSF and IL-4, and then stimulated with acemannan, sulfated acemannan, and LPS, respectively. The resultant DCs were examined for phenotypic and functional properties. Phenotypic analysis for the expression of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, CD40 and CD54 confirmed that acemannan could induce maturation of immature DCs. Functional maturation of immature DCs was supported by increased allogeneic mixed lymphocyte reaction (MLR) and IL-12 production. The differentiation-inducing activity of acemannan was almost completely abolished by chemical sulfation. Based on these results, we propose that the adjuvant activity of acemannan is at least in part due to its capacity to promote differentiation of immature DCs.And:
Int J Tissue React. 1998;20(4):115-8. Related Articles, Links
The therapeutic potential of Aloe Vera in tumor-bearing rats.
Corsi MM, Bertelli AA, Gaja G, Fulgenzi A, Ferrero ME.
Institute of General Pathology, Medical Faculty, University of Milan, Italy.
Aloe Vera has been claimed to contain several important therapeutic properties, including anticancer effects. The effect of Aloe Vera administration was studied on a pleural tumor in rat. Growth of Yoshida AH-130 ascite hepatoma cells injected (2 x 10(5) in 0.1 ml) into pleura of male inbred Fisher rats was evaluated at different times (7th and 14th days). Data show that the use of Aloe Vera proved a therapeutic method, and that the present experimental model could be useful in the study of other therapeutics treatments in vivo.And:Vopr Onkol. 1986;32(12):38-40. Related Articles, Links
[Antimetastatic properties of aloe juice]
[Abstract in Russian]
Gribel' NV, Pashinskii VG.
An evaluation of antimetastatic properties of succus Aloes was carried out using three types of experimental tumors of mice and rats. It was found that succus Aloes treatment contributes to reduction of tumor mass, metastatic foci and metastasis frequency at different stages of tumor progress without affecting major tumor growth. Succus Aloes potentiates the antitumor effect of 5-fluorouracil and cyclophosphamide as components of combination chemotherapy.The following contrasting abstract found accentuating genotoxicity of an aloe derivative, therefore, proposing a contrary view that aloe might instead be a risk for cancer induction:
Mutat Res. 1996 Dec 20;371(3-4):165-73. Related Articles, Links
Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II mediated?
Muller SO, Eckert I, Lutz WK, Stopper H.
Department of Toxicology, University of Wurzburg, Germany.
1,8-Dihydroxyanthraquinones are under debate as plant-derived carcinogens that are found in laxatives, food colors, and possibly vegetables. Published genotoxicity data are controversial, and so three of them (emodin, danthron and aloe-emodin) were tested in a number of in vitro assay systems. All three compounds induced tk-mutations in mouse lymphoma L5178Y cells. Induction of micronuclei also occurred in the same cell line, and was dose-dependent, with the potency ranking being danthron > aloe-emodin > emodin. In a DNA decatenation assay with a network of mitochondrial DNA of C. fasciulata, all three test compounds inhibited the topoisomerase II-mediated decatenation. Danthron and aloe-emodin, but not emodin, increased the fraction of DNA moving into comet tails when tested at concentrations around 50 microM in single-cell gel-electrophoresis assays (SCGE; comet assay). Comet assays were also used in modified form to determine whether pretreatment of the cells with the test compounds would reduce the effects of etoposide, a potent topoisomerase II inhibitor. All three test chemicals were effective in this pretreatment protocol, with danthron again being the most potent(Editor’s note: Not present in Aloe). Given clear cut evidence of their genotoxic activity, further research on the human cancer risk of these compounds may be warranted.A cautionary abstract elucidates opposing mechanisms relevant to the anticancer properties of aloe emodin:
Cell Mol Life Sci. 2004 Jul;61(14):1805-15. Related Articles, Links
Aloe-emodin prevents cytokine-induced tumor cell death: the inhibition of auto-toxic nitric oxide release as a potential mechanism.
Mijatovic S, Maksimovic-Ivanic D, Radovic J, Popadic D, Momcilovic M, Harhaji L, Miljkovic D, Trajkovic V.
Department of Neurobiology and Immunology, Institute for Biological Research, 29. Novembra 142, 11000, Belgrade, Serbia and Montenegro. email@example.com
Aloe-emodin (AE) is a plant-derived hydroxyanthraquinone with potential anticancer activity. We investigated the ability of AE to modulate survival of mouse L929 fibrosarcoma and rat C6 astrocytoma cells through interference with the activation of inducible nitric oxide (NO) synthase (NOS) and subsequent production of tumoricidal free radical NO. Somewhat surprisingly, AE in a dose-dependent manner rescued interferon-gamma + interleukin-1-stimulated L929 cells from NO-dependent killing by reducing their autotoxic NO release. The observed protective effect was less pronounced in C6 cells, due to their higher sensitivity to a direct toxic action of the drug. AE-mediated inhibition of tumor cell NO release coincided with a reduction in cytokine-induced accumulation of transcription and translation products of genes encoding inducible NOS and its transcription factor IRF-1, while activation of NF-kappaB remained unaltered. These data indicate that the influence of AE on tumor growth might be more complex that previously recognized, the net effect being determined by the balance between the two opposing actions of the drug: its capacity to directly kill tumor cells, but also to protect them from NO-mediated toxicity.
The next recent study shows the immune modulatory efficacy and antitumor effects of aloe. Int Immunopharmacol. 2005 Feb;5(2):271-9. Related Articles, Links
Identification of optimal molecular size of modified Aloe polysaccharides with maximum immunomodulatory activity.
Im SA, Oh ST, Song S, Kim MR, Kim DS, Woo SS, Jo TH, Park YI, Lee CK.
College of Pharmacy, Chungbuk National University, Cheongju 361-763, South Korea.
Polysaccharides isolated from the gel of Aloe species have been known to have diverse biological activities, including immunomodulatory and antitumor activities. The molecular size-immunomodulatory activity relationship of modified Aloe polysaccharide (MAP) was examined in this study. Crude MAP (G2E1) was prepared from the gel of Aloe vera that was partially digested with cellulase. Proteins in crude MAP were removed by passage through a DEAE-Sephacel column, and then the protein-free MAP (G2E1D) was further separated into three fractions, G2E1DS3 molecular weight (MW>/=400 KDa), G2E1DS2 (5 KDa=MW< href="mailto:firstname.lastname@example.org">email@example.com
OBJECTIVE: To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale. RESULTS: A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. CONCLUSIONS: There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.Here is a fascinating finding about aloe and the neurodegenerative consequences of diabetes that affect memory, various behaviors, and learning abilities in a diabetic mouse model. Again relevance to human biology is suggestive, but not proven.
J Clin Neurosci. 2004 May;11(4):397-402. Related Articles, Links
Susceptibility of hippocampus and cerebral cortex to oxidative damage in streptozotocin treated mice: prevention by extracts of Withania somnifera and Aloe vera.
Parihar MS, Chaudhary M, Shetty R, Hemnani T.
Biochemistry Division, Faculty of Life Science, School of Studies in Zoology, Vikram University, Ujjain 456 010, India.
Diabetes mellitus is reported to impair the memory function in experimental animals. Since the mammalian hippocampus and cerebral cortex play a pivotal role in a diverse set of cognitive functions, such as novelty detection and memory, we examined the vulnerability of cortex and hippocampus regions of the brain to oxidative damage in streptozotocin (STZ) diabetic mice. We next examined the attenuating effect of extracts of Withania somnifera and Aloe vera on prevention of hippocampal and cortical cell degenerations. Doses of both plant extracts given to experimental animals were based on the evaluation of their total antioxidant activity and also their potency to reduce Fe(3+). We assayed lipid peroxidation (LPO) and protein carbonyl (PC) in both regions of the brain and observed the changes in memory and motor behavioral functions in diabetic and control mice. The results showed a significant ( [Formula: see text] ) increase in LPO and PC in hippocampus and cortical regions of STZ diabetic mice. We also found a significant impairment in both motor and memory behavioral functions in diabetic mice. However, when diabetic mice were supplemented with the extracts of Withania somnifera and Aloe vera, the oxidative damage in both brain regions was reduced as marked by a significant ( [Formula: see text] ) declines in both LPO and PC. The combination of extracts of Withania somnifera and Aloe vera was more effective in reducing oxidative damage in brain regions than the supplementation of single plant extract. The combination also lowered the blood glucose level in comparison to STZ diabetic mice. Memory impairment and motor dysfunction were also improved by the plant extracts supplementation. We conclude that impairments in the hippocampus and cortex in STZ diabetic mice are associated with an increased free radical mediated oxidative damage and that the supplementation of plant extracts showed preventive effects in attenuating oxidative damage in both brain regions possibly via antioxidative mechanisms.Antihypertensive properties Blood pressure control may also be an attribute of aloe.
Planta Med. 2001 Nov;67(8):757-60. Related Articles, Links
Hypotensive effect of chemical constituents from Aloe barbadensis.
Saleem R, Faizi S, Siddiqui BS, Ahmed M, Hussain SA, Qazi A, Dar A, Ahmad SI, Qazi MH, Akhtar S, Hasnain SN.
Dr. H.M.I. Institute of Pharmacology and Herbal Sciences, Hamdard University, Karachi, Pakistan. firstname.lastname@example.org
Hypotensive effects of aloeemodin, aloin A, elgonica dimer A and bisbenzopyran from Aloe barbadensis have been studied. Aloeemodin has emerged as a potent hypotensive agent in current pharmacological investigations and caused 26 %, 52 %, and 79 % falls in mean arterial blood pressure at the corresponding doses of 0.5, 1, and 3 mg/kg in rats. The paper also describes the absolute configuration of elgonica dimer A (1).Antioxidant properties relating to anti-atherogenesis
Note that in 1985 when the above observations were made, the knowledge contained in this Library about all the various compounds within aloe was not known. This Library has the advantage of hindsight. We can emphasize the findings in the above 1985 study to connect the dots of what we now know about lipid peroxidation, superoxide formation, oxygen and nitrogen free radicals, and their production of inflammation. Now we know that the inner lining of critical blood vessels, when inflamed, stimulates the collection of these lipid products and calcium and promotes inflammatory responses, which ultimately create the plaque.
The following study suggests a role for lifelong aloe supplementation as a cardioprotective agent based upon its intra-hepatic (inside the liver) cholesterol-lowering ability as well as its antioxidant properties.
J Nutr Sci Vitaminol (Tokyo). 2003 Aug;49(4):292-6. Related Articles, Links
Efficacy of dietary aloe vera supplementation on hepatic cholesterol and oxidative status in aged rats.
Lim BO, Seong NS, Choue RW, Kim JD, Lee HY, Kim SY, Yu BP, Jeon TI, Park DK.
Graduate School of East-West Medical Science, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-Ku, Korea. email@example.com
In the current study, we show the anti-oxidative and hypocholesterol effects of aloe vera in the liver. Male specific pathogen-free (SPF) Fischer 344 rats were randomly assigned to one of four groups: Group A (control) was fed test chow without aloe supplementation; Group B was fed a diet containing a 1% (per weight basis) freeze-dried aloe filet; Group C was fed a diet containing a 1% (per weight basis) charcoal-processed, freeze-dried aloe filet; and Group D was fed a diet containing a charcoal-processed freeze-dried, whole leaf aloe (0.02% per weight basis) in the drinking water. Our results show that a life-long intake of aloe had superior anti-oxidative action against lipid peroxidation in vivo, as indicated by reduced levels of hepatic phosphatidylcholine hydroperoxide. Additional anti-oxidative action was evidenced by enhanced superoxide dismutase (SOD) and catalase activity in groups B and C. Furthermore, our study revealed that hepatic cholesterol significantly increased in the control group during aging in contrast to the aloe-supplemented groups, which showed approximately 30% lower cholesterol levels, thereby an effective hypocholesteremic efficacy. In this report, we suggest that life-long dietary aloe supplementation suppresses free radical-induced oxidative damage and age-related increases in hepatic cholesterol.Both enhanced lipid peroxidation and microvascular disease leads to kidney damage and renal failure in type 2 diabetes. The following abstract shows how aloe’s antioxidant properties can account for the ability to protect kidney tissue from damage in the diabetic rat model.
Indian J Exp Biol. 2004 Jan;42(1):48-52. Related Articles, Links
Effect of Aloe vera (L.) Burm. fil. leaf gel and pulp extracts on kidney in type-II diabetic rat models.
Bolkent S, Akev N, Ozsoy N, Sengezer-Inceli M, Can A, Alper O, Yanardag R.
Department of Biology, Faculty of Science, Istanbul University, 34459-Vezneciler, Istanbul, Turkey.
Significant degenerative changes were observed in the kidney tissue of untreated neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. These degenerative changes were diminished in the kidney tissue of diabetic animals given glibenclamide and Aloe leaf gel and pulp extracts. Kidney lipid peroxidation levels were increased in diabetic rats compared to healthy rats; these levels were higher in rats treated with glibenclamide than in those which received Aloe extracts. Serum urea and creatinine levels were higher in diabetic rats in comparison to healthy rats. The administration of Aloe gel extract and glibenclamide decreased serum urea and creatinine levels in comparison to diabetic controls. Only A. vera leaf gel extract showed improvement both in histological and biochemical parameters suggesting a protective effect of A. vera
Antibacterial / antiviral / antifungal / antiparasitic propertiesMore than a decade has passed since H. pylori, the cause of bacterial infections of the stomach, was recognized as a possible cause of chronic gastritis and recurrent peptic ulcer disease. Aloe now is recognized as an effective treatment for H. pylori infections since it can inhibit the growth of this pathogen. The general antibiotic potential of aloe is also suggested. Planta Med. 1998 Mar;64(2):176-8. Related Articles, Links
Aloe-emodin effects on arylamine N-acetyltransferase activity in the bacterium Helicobacter pylori.
Wang HH, Chung JG, Ho CC, Wu LT, Chang SH.
Arylamine N-acetyltransferase (NAT) activities with p-aminobenzoic acid (PABA) and 2-aminofluorene (AF) were determined in H. pylori collected from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without different concentrations of aloe-emodin co-treatment showed different percentages of AF and PABA acetylation. The data indicate that there was decreased NAT activity associated with increased aloe-emodin in H. pylori cytosols. Inhibition of growth study from H. pylori demonstrated that aloe-emodin elicited dose-dependent growth inhibition in H. pylori cultures. The report is the first finding of aloe-emodin inhibition of arylamine NAT activity in a strain of H. pylori.The structural and functional similarities of aloe to tetracyclines may explain the bacteriostatic properties of aloe.
Life Sci. 2003 Jan 3;72(7):843-50. Related Articles, Links
Inhibition of collagenase and metalloproteinases by aloins and aloe gel.
Barrantes E, Guinea M.
Department of Pharmacology, School of Pharmacy, University of Alcala, Ctra. Madrid-Barcelona Km 33.6, 28871 Alcala de Henares, Spain.
The effects of Aloe barbadensis gel and aloe gel constituents on the activity of microbial and human metalloproteinases have been investigated. Clostridium histolyticum collagenase (ChC) results dose-dependently inhibited by aloe gel and the activity-guided fractionation led to an active fraction enriched in phenolics and aloins. Aloins have been shown to be able to bind and to inhibit ChC reversibly and non-competitively. Aloe gel and aloins are also effective inhibitors of stimulated granulocyte matrix metalloproteinases (MMPs). The remarkable structural resemblances between aloins and the pharmacophore structure of inhibitory tetracyclines, suggest that the inhibitory effects of aloins are via an interaction between the carbonyl group at C(9) and an adjacent hydroxyl group of anthrone (C(1) or C(8)) at the secondary binding site of enzyme, destabilizing the structure of granulocyte MMPs.The inner gel of aloe is effective for two more pathogens described below.
Antimicrob Agents Chemother. 2003 Mar;47(3):1137-9. Related Articles, Links
In vitro susceptibilities of Shigella flexneri and Streptococcus pyogenes to inner gel of Aloe barbadensis Miller.
Ferro VA, Bradbury F, Cameron P, Shakir E, Rahman SR, Stimson WH.
Department of Immunology, University of Strathclyde, Glasgow G4 ONR, United Kingdom. firstname.lastname@example.org
Aloe barbadensis Miller (or Aloe vera) has widespread use in health products, and despite numerous reports on the whole plant, little work has been performed on the inner gel, which has been used extensively in these products. This report describes the in vitro susceptibilities of two bacteria to this component.
The mechanisms of antibiotic activity of aloe based on two of the anthraquinones, aloin and aloe emodin:
Zhongguo Zhong Yao Za Zhi. 2003 Nov;28(11):1034-7. Related Articles, Links
[Relationship between antibacterial activity of aloe and its anthaquinone compounds]
[Abstract in Chinese]
Tian B, Hua YJ, Ma XQ, Wang GL.
Department of Applied Bioscience, Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310029, Zhejiang, China. email@example.com
OBJECTIVE: To investigate the relationship between the antibacterial activity of aloe and its contents of anthaquinone compounds, measure and compare antibacterial activities of aloin and aloe-emodin, and analyse the effect of glycoside on the antibacterial activity of aloin. METHOD: The antibacterial activities of the extracts from the outer leaf of Aloe saponaria Haw, aloin and aloe-emodin against three Gram-negative and two Gram-positive bacteria were investigated with the method of agar diffusion. The antibacterial effect of aloin on E. coli was further studied with scanning electron microscopy. RESULT: The antibacterial activities of aloe showed to be dependent on the dose of anthraquinone, aloin (1 g x L(-1)) exhibited higher antibacterial activity [inhibition diameter > (7. 1 +/- 0.15) mm] than Aloe-emodin (inhibition diameter < href="mailto:firstname.lastname@example.org">email@example.com
Plants containing aloin A, aloe emodin, and structurally related anthraquinones have long been used as traditional medicines and in the formulation of retail products such as laxatives, dietary supplements, and cosmetics. Since a recent study indicated that topically applied aloe emodin increases the sensitivity of skin to UV light, we examined the events following photoexcitation of aloin A and aloe emodin. We determined that incubation of human skin fibroblasts with 20 microM aloe emodin for 18 h followed by irradiation with UV or visible light resulted in significant photocytotoxicity. This photocytotoxicity was accompanied by oxidative damage in both cellular DNA and RNA. In contrast, no photocytotoxicity was observed following incubation with up to 500 microM aloin A and irradiation with UVA light. In an attempt to explain the different photobiological properties of aloin A and aloe emodin, laser flash photolysis experiments were performed. We determined that the triplet state of aloe emodin was readily formed following photoexcitation. However, no transient intermediates were formed following photoexcitation of aloin A. Therefore, generation of reactive oxygen species and oxidative damage after irradiation of aloin A is unlikely. Although aloin A was not directly photocytotoxic, we found that human skin fibroblasts can metabolize aloin A to aloe emodin.Promoter of chemical and drug detoxification of liver
Aloe facilitates detoxification providing chemoprotection against carcinogens and other toxins, including drugs.
Phytomedicine. 2000 Jun;7(3):209-19. Related Articles, Links
Chemomodulatory action of Aloe vera on the profiles of enzymes associated with carcinogen metabolism and antioxidant status regulation in mice.
Singh RP, Dhanalakshmi S, Rao AR.
Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
The effect of two doses (30 microl and 60 microl/day/mice daily for 14 days) of the fresh leaf pulp extract of Aloe vera was examined on carcinogen-metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of mice. The modulatory effect of the pulp extract was also examined on extrahepatic organs (lung, kidney and forestomach) for the activities of glutathione S-transferase, DT-diophorase, superoxide dismutase and catalase. The positive control mice were treated with butylated hydroxyanisole (BHA). Significant increases in the levels of acid soluble sulfhydryl (-SH) content, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, glutathione S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase (GR) were observed in the liver. Aloe vera significantly reduced the levels of cytochrome P450 and cytochrome b5. Thus, Aloe vera is clearly an inducer of phase-II enzyme system. Treatment with both doses of Aloe caused a decrease in malondialdehyde (MDA) formation and the activity of lactate dehydrogenase in the liver, suggesting its role in protection against prooxidant-induced membrane and cellular damage. The microsomal and cytosolic protein was significantly enhanced by Aloe vera, indicating the possibility of its involvement in the induction of protein synthesis. BHA, an antioxidant compound, provided the authenticity of our assay protocol and response of animals against modulator. The pulp extract was effective in inducing GST, DTD, SOD and catalase as measured in extrahepatic organs. Thus, besides liver, other organs (lung, kidney and forestomach) were also influenced favorably by Aloe vera in order to detoxify reactive metabolites, including chemical carcinogens and drugs.Potential additional treatment for autoimmune gastrointestinal inflammatory diseases and duodenal and gastric ulcers
Aloe is not only anti-inflammatory for skin, but in the following abstract we see the emergence of the anti-inflammatory benefits to inflammatory bowel diseases such as ulcerative colitis and regional enteritis (Crohn’s disease).
Aliment Pharmacol Ther. 2004 Mar 1;19(5):521-7. Related Articles, Links
Anti-inflammatory effects of aloe vera gel in human colorectal mucosa in vitro.
Langmead L, Makins RJ, Rampton DS.
Centre for Adult and Paediatric Gastroenterology, Institute of Cellular and Molecular Science, Barts and the London, Queen Mary School of Medicine and Dentistry, London, UK.
BACKGROUND: Oral aloe vera gel is widely used by patients with inflammatory bowel disease and is under therapeutic evaluation for this condition. AIM: To assess the effects of aloe vera in vitro on the production of reactive oxygen metabolites, eicosanoids and interleukin-8, all of which may be pathogenic in inflammatory bowel disease. METHODS: The anti-oxidant activity of aloe vera was assessed in two cell-free, radical-generating systems and by the chemiluminescence of incubated colorectal mucosal biopsies. Eicosanoid production by biopsies and interleukin-8 release by CaCo2 epithelial cells in the presence of aloe vera were measured by enzyme-linked immunosorbent assay. RESULTS: Aloe vera gel had a dose-dependent inhibitory effect on reactive oxygen metabolite production; 50% inhibition occurred at 1 in 1000 dilution in the phycoerythrin assay and at 1 in 10-50 dilution with biopsies. Aloe vera inhibited the production of prostaglandin E2 by 30% at 1 in 50 dilution (P = 0.03), but had no effect on thromboxane B2 production. The release of interleukin-8 by CaCo2 cells fell by 20% (P < changes="1)">/= 3 points; response was defined as remission or improvement), Baron score, histology score, haemoglobin, platelet count, erythrocyte sedimentation rate, C-reactive protein and albumin. RESULTS: Clinical remission, improvement and response occurred in nine (30%), 11 (37%) and 14 (47%), respectively, of 30 patients given aloe vera, compared with one (7%) [P = 0.09; odds ratio, 5.6 (0.6-49)], one (7%) [P = 0.06; odds ratio, 7.5 (0.9-66)] and two (14%) [P < p =" 0.01" p =" 0.03," href="mailto:firstname.lastname@example.org">email@example.com
Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane [dextran] sulfate (DDS) (3 days), followed by 1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment.The above study suggests that the mechanism is such that pretreatment, which in human terms means prevention in nature, should be considered in patients with strong family histories of ulcerative colitis but who have not yet exhibited symptoms.
Also relating to gastritis and peptic ulcer conditions, the following suggests aloe may be an acid reducer like the drugs Zantac®, Pepcid®, and Tagamet®. Its use as a remedy for GI ailments is substantiated by the abstract below.
Use for injury to the stomach, esophagus, or duodenum from too much acid, which leads to gastritis, esophagitis, or ulcers, is suggested next.
J Ethnopharmacol. 2004 Jul;93(1):33-7. Related Articles, Links
The effect of Aloe vera A. Berger (Liliaceae) on gastric acid secretion and acute gastric mucosal injury in rats.
Yusuf S, Agunu A, Diana M.
Department of Human Physiology, Ahmadu Bello University, Zaria, Nigeria. firstname.lastname@example.org
The effect of varying doses of ethanol extract of Aloe vera (Liliaceae) on acute gastric mucosal lesions induced by 0.6 M HCl and acid output was studied in the pylorus ligated and lumen perfuse rats, respectively. Acid secretion was determined by titration of the collected gastric juice to pH 7.0. Intraperitoneal injection of Aloe vera, dose dependently inhibited gastric acid secretion. [Editor’s note: not an effect induced by topical contact with injured mucosa] The plant was more active as a gastroprotective agent at lower concentration against mucosal injury induced by 0.6 M HCl. In conclusion, Aloe vera is endowed with gastric acid anti-secretory activity and could protect the gastric mucosa at low concentrations against injurious agents.Managing psoriasis
Trop Med Int Health. 1996 Aug;1(4):505-9. Related Articles, Links
Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study.
Syed TA, Ahmad SA, Holt AH, Ahmad SA, Ahmad SH, Afzal M.
Department of Clinical Physiology, Malmo University Hospital, Sweden.
The purpose of this double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerability of topical Aloe vera extract 0.5% in a hydrophilic cream to cure patients with psoriasis vulgaris. Sixty patients (36M/24F) aged 18-50 years (mean 25.6) with slight to moderate chronic plaque-type psoriasis and PASI (Psoriasis Area and Severity Index) scores between 4.8 and 16.7 (mean 9.3) were enrolled and randomized to two parallel groups. The mean duration of the disease prior to enrollment was 8.5 years (range 1-21). Patients were provided with a precoded 100g tube, placebo or active (with 0.5% Aloe vera extract), and they self-administered trial medication topically (without occlusion) at home 3 times daily for 5 consecutive days per week (maximum 4 weeks active treatment). Patients were examined on a weekly basis and those showing a progressive reduction of lesions, desquamation followed by decreased erythema, infiltration and lowered PASI score were considered healed. The study was scheduled for 16 weeks with 12 months of follow-up on a monthly basis. The treatment was well tolerated by all the patients, with no adverse drug-related symptoms and no dropouts. By the end of the study, the Aloe vera extract cream had cured 25/30 patients (83.3%) compared to the placebo cure rate of 2/30 (6.6%) (P < href="mailto:email@example.com">firstname.lastname@example.org
Products derived from the inner gel of the Aloe vera L. plant have demonstrated multiple clinical activities, and are used routinely to accelerate wound healing. However, typical of natural products, the complex nature of Aloe vera gels may contribute to diverse pharmacologic activities. Our focus on the hematopoietic activities of Aloe vera extracts is extended by these functional studies, which used purified fractions from Aloe vera gel and included a preliminary organ-specific in vitro molecular profile. Studies using a >99% pure carbohydrate fraction from Aloe vera extracts revealed increased hematopoietic and hematologic activity compared to the starting material. In addition, this fraction differentially regulated liver and lung cytokine mRNA levels, resulting in significant increases in message for hematopoietic cytokines [granulocyte colony stimulating factor (G-CSF) and stem cell factor (SCF)]. This profile of activity differed from another fraction obtained from Aloe vera, suggesting the potential for diverse pharmacologic activity. The molecular studies were undertaken using co-cultures of organ slices to limit the amount of purified material required. In summary, these studies revealed significant hematopoietic activity by both pharmacologic and molecular analysis using a >99% pure carbohydrate fraction from Aloe vera gels.Analgesic propertiesOne of the cardinal features of inflammation is pain. In addition to aloe being a proven anti-inflammatory agent, it is an analgesic as well. The following abstract gives a possible neurophysiological explanation of how aloe works to relieve pain. The study also demonstrates a possible mechanism for the analgesic effect of aloe in inflammatory conditions. This paper uses an electrophysiological study of end plate (nerve ending) potentials in a neurophysiological model using crayfish neuromuscular junctions (where the nerves activating muscles meet the muscle cells).Phytother Res. 1999 Nov;13(7):580-3. Related Articles, Links
Initial characterization of the effects of Aloe vera at a crayfish neuromuscular junction.
Friedman RN, Si K.
Section of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202-5112, USA. email@example.com
This study examines the effects of Aloe vera on neurotransmission processes in a well-established invertebrate neuromuscular junction preparation. We studied concentration-response relationships of an Aloe vera extract on excitatory junctional potentials (EJPs) at the opener muscle of the dactyl in the first and second walking limbs of crayfish (Procambarus clarkii and simulans). We observed concentration-dependent depolarizations of the muscle fibre membrane resting potential, depression of EJP amplitudes and an increase in latency to onset of the EJP following electrical stimulation of the isolated excitatory axon in the meropodite. These effects occurred with Aloe concentrations within the 1%-10% (wt-vol) range. Effects of lower concentrations, ranging to a minimum of 0.01% were equivocal. The effects of Aloe were at least partially, and in a majority of cases totally, reversible. EJPs reduced by Aloe could be restored by increasing the nerve stimulation amplitude. This, along with the latency increase, suggests a depression of action potential generation and conduction. The results provide a preliminary characterization of the effects of Aloe vera on the neurotransmission process and suggest that these effects may at least partially account for Aloe's analgesic and antiinflammatory effects. This study shows that the crayfish NMJ preparation should be useful for further elucidating the location(s) and mechanism(s) of action of Aloe on the nervous system. Copyright 1999 John Wiley & Sons, Ltd.Spermicidal contraceptiveA study suggests the possible combination of aloe and zinc acetate as a nonirritating vaginal spermicidal contraceptive:
Contraception. 1996 Apr;53(4):231-6. Related Articles, Links
Zinc acetate and lyophilized aloe barbadensis as vaginal contraceptive.
Fahim MS, Wang M.
Center of Reproductive Science and Technology, School of Medicine, University of Missouri, Columbia 65212, USA.
Twenty samples of fresh ejaculate, donated by healthy volunteers ranging in age from 20-30 years, were obtained from the Center for Fertility & Cryobiology, University of Missouri, Columbia, Missouri. Average semen volume was 2.49 ml; average sperm motility was 71.32%; and average sperm density was 113.71 x 10(6) /ml. Testing for spermicidal effectiveness of a 1% concentration of zinc acetate, zinc sulfate, zinc chloride, and zinc gluconate proved that only zinc acetate was spermicidal. It appears this is due to the acetate in zinc acetate which may decrease oxygen utilization by sperm. Zinc acetate in vitro was antiviral while lyophilized aloe barbadensis was not. Lyophilized aloe barbadensis at concentrations of 7.5% and 10% proved to be spermicidal due to the multiple micro elements (boron, barium, calcium, chromium, copper, iron, potassium, magnesium, manganese, phosphorus, and zinc) which were toxic to the tail causing instant immobilization. The two compounds did not irritate or cause ulceration of rabbit vaginal epithelium. These results suggest the possibility of using zinc acetate and lyophilized aloe barbadensis as a new, effective and safe vaginal contraceptive.----------------------------------------------------------
Agronomic information pertaining to variance of active compounds based upon geographical origin of aloe plants considered
Planta Med. 1995 Jun;61(3):250-3. Related Articles, Links
Geographical variation in the major compounds of Aloe ferox leaf exudate.
van Wyk BE, van Rheede van Oudtshoorn MC, Smith GF.
Department of Botany, Rand Afrikaans University, Johannesburg, South Africa.
Geographical variation in fresh Aloe ferox leaf exudate of which the dried product is commercially known as Cape Aloes, was investigated throughout the natural distribution range of the species. The composition of the major compounds is remarkably invariable, with aloeresin A, aloesin, and aloin (both epimers A and B) contributing between 70% and 97% of total dry weight, in a ratio of approximately 4:3:2, respectively. Minor compounds are less evenly distributed, with aloinoside A and aloinoside B more frequent in the western parts of the distribution area and aloeresin C and 5-hydroxyaloin A generally present in small quantities throughout the distribution area. The aloin content of the exudate is clearly related to provenance but there are no distinct geographical discontinuities. The selection of high-yielding provenances, with total aloin levels above 25%, is recommended for commercial cultivation.