Aloe aus pharmazeutischer Sicht
14.4.2002
1. Sven Jaehnichen : "Wundermittel Aloe Vera Saft" 2. Die Monographien der WHO : "Aloe" "Aloe vera Gel"
Sven Jaehnichen hat mir freundlicherweise die Wiedergabe eines auf seinem Usenet-Artikel basierenden Texts über aloe vera aus pharmazeutischer Sicht erlaubt.
Ich wurde in letzter Zeit immer wieder mit dem Thema Aloe Vera Saft konfrontiert. Insbesondere im AOL-Pinboard häufen Anfragen zum Thema Aloe Vera Saft (bzw. Aloe Vera Gel) - nicht selten steckt da ein MLM dahinter, wie weitere Anfragen ergaben. An einigen Ständen der Berliner Food-Messe "Grüne Woche" waren jene Mittel ebenfalls zu sehen. Ihm werden verschiedenste antidiabetische, immunstimmulierende und entzündungshemmende Wirkungen zugeschrieben - u.a. auch gegen Krebs und AIDS - während der Vertrieb als Lebensmittel (bzw. Nahrungsergänzungsmittel (NEM)) erfolgt. Also wieder mal ein Grund, dies genauer unter die Lupe zu nehmen.
Was ist Aloe Vera? Was ist Aloe?
Als "Aloe Vera" bezeichnet man den genuinen gelartigen Pflanzensaft der Heilpflanze Aloe barbadensis MILLER. Im Gegensatz zu dem als Abführmittel verwendeten "Aloe" (Wirkstoffe: Aloine) wird Aloe Vera nicht durch verschiedene Methoden zu einem Konzentrat eingeengt. Auf zahlreichen Internetseiten der Vertreiber ist dies falsch dargestellt.
Es muß darauf geachtet werden, daß bei der Bearbeitung aus der Blattrinde kein Saft in das gewonnene Gel gelangt. Hierzu die Monographie der WHO:
Das Lebensmittelrecht verlangt einen Aloingehalt von weniger als 0,1ppm.
Es gibt "Aloe-Vera"-Gele, die nicht nach Filetierung gewonnen wurden und daher Aloine enthalten.
Es werden sogar einige aloinhaltige Aloe vera Produkte vertrieben, die aus dem ganzen Blatt gewonnen wurden.
Woraus besteht Aloe Vera?
Aloe Vera Saft enthält neben viel Wasser (95%) und einigen Heteropolysacchariden (z.B. Acemannan; 5%)[1] eine Reihe von Inhaltsstoffen in geringer Konzentration. Genannt werden insbesondere Vitamine, Mineralien (beide nicht in überdurchschnittlichen Konzentrationen), Enzyme, Aloine und Saponine.
Ist Aloe Vera unbedenklich?
Nicht alle Inhaltsstoffe sind unbedenklich. Während der Wirkstoff Acemannan selbst in i.v.-Dosen bis zu 10mg/kg beim Hund keine toxischen Effekte zeigte [4], so sind die Aloine für eine ausgeprägte abführende Wirkung verantwortlich, sie zeigen eine Wirksamkeit im unteren Milligrammbereich. Eine Überdosierung kann schwere Folgen haben. Im NEM-Bereich gab es in Deutschland bereits einen solchen Fall ("Zitronen-Schlank-Kapseln", die zusätzlich Aloe enthielten): der Hersteller hatte sich bei der Dosierung verrechnet.
Die meisten Hersteller geben zwar an, dass sie diese Aloine abtrennen. Wie sie dies machen, verraten sie nur selten. Die Trennung über Aktivkohle, wie es ein Hersteller praktiziert dürfte wenig effektiv sein - sie ist für Eiweißbestandteile (Enzyme) wohl besser geeignet. Noch weniger Hersteller weisen valide Analysenzertifikate vor. Auch das Bundesinstitut für gesundheitlichen Verbraucherschutz (BgVV) meldete Zweifel an, das diese Verfahren überhaupt geeignet sind, Aloin abzutrennen [1] und verweist darauf, das in Lebensmitteln ein Höchstwert von 0,1mg/kg toleriert wird.
Zertifikate - sofern diese mal vorliegen - bestätigen allerdings nur einen Aloingehalt von weniger als 2mg/kg.
Weitere toxikologisch bedeutsame Substanzen konnten in Aloe Vera Saft Präparaten gefunden werden [2], die den Nutzen weiter eingrenzen können.
Die Qualität eines Aloe Vera Saftes ist für den Laien schlecht einschätzbar. Auch der Fachmann wird in der Regel diese Qualität nicht beurteilen können, da im Grau-Bereich der NEMs kaum gesicherte Daten zu erhalten sind.
Eine Dokumentation zu unerwünschten Wirkungen ist auf den Internetseiten der amerikanischen Lebensmittel- und Gesundheitsbehörde FDA zu finden [9]. Hier werden z.Z. 30 Fälle aufgelistet, die im Zusammenhang mit Aloe vera gesehen werden.
Dazu zählen u.a.
Wie wirkt Aloe Vera?
Aloe Vera ist ein vieluntersuchtes Objekt. Sämtliche Forschungsergebnisse hier wiederzugeben ist ein Ding der Unmöglickeit, zumal die meisten sich auf wissenschaftlich dünnen Eis befinden.
In in-vitro Untersuchungen ("im Reagenzglas") konnten verschiede Wirkungen von Aloe Vera beobachtet werden, die praktisch alle auf das Polysaccharid Acemannan, das auch als Gebisskleber verwendet wird, zurückgeführt werden. So konnte an isolieten Zellen eine Stimmulation des Immunsystems durch Macrophagenstimmulation [3] und durch Freisetzung von Mediatoren gezeigt werden. Ebenso einige Berichte über eine positive Beeinflussung von Viren- und Tumorerkrankungen am Tier nach parenteraler Verabreichung ("per Spritze") von Acemannan. Wundheilungsfördernde Effekte konnten ebenso Tierexperimentell gezeigt werden [10].
Nach diesen Erfolgen wurden auch Studien am Menschen betrieben. Diese Studien wurden gut geplant und liefern die einzig interessante Aussage: Wirkt es überhaupt?
Auch andere Studien bestätigen dies [8].
Da offensichtlich keine einzige klinische Studie existiert, die die Wirksamkeit von Aloe Vera bei irgendeiner Indikation belegt(!), wohl aber einige in-vitro- und Tierversuche positive Ergebnisse lieferten, ist der therapeutische Nutzen zumindest in Frage zu stellen.
Möglicherweise wird das Polysaccharid Acemannan, wie viel anderen Verwandten, gar nicht erst nach oraler Gabe vom Körper aufgenommen - an dieser Hürde scheitern die meisten potentiellen Arzneistoffe. Aber dies wäre reine Spekulation und würde von vorn herein Aloe Vera Saft als unwirksam bezeichnen.
Wie wird Aloe Vera vertrieben?
Aloe Vera Saft und Gel wird in Deutschland vom BgVV auf Grund seiner Zweckbestimmung als Arzneimittel eingestuft [1]. Da diese Mittel keine Zulassung als solche besitzen (dazu wären u.a. ein Wirksamkeitsnachweis und ein Unbedenklichkeitsnachweis nötig), wird versucht sie illegal als Lebensmittel oder genauer als Nahrungsergänzungsmittel abzusetzen, da hierfür diese Nachweise nicht erforderlich sind. Das BgVV erwähnt des weiteren, dass keine ernährungsphysiologische Bedeutung für Aloe Vera existiert [1]. Für Lebensmittel insbesondere für NEMs darf keine gesundheitsbezogene Werbung betrieben werden, pharmakologische Effekte dürfen nicht vorhanden sein (§§17,18 LMBG) - sonst wären sie ja Arzneimittel (§2 AMG), womit wir wieder beim ersten Satz dieses Absatzes wären. Aber wo kein Kläger ist, ist auch kein Richter.
Theoretisch wäre ein Vertrieb als "Novel Food" gemäß einer EU-Richtlinie möglich. Dazu müsste nur ein Unbedenklichkeitsnachweis vorliegen (was bei ordnungsgemäßer Qualität nicht das Problem sein dürfte). Diese Lebensmittel dürfen mit Heilaussagen beworben werden, solange sie sich beweisen lassen - sonst gibts Ärger mit dem HWG.
Auch der Preis der Produkte streut erheblich. Für einen Liter dieses Getränkes muss man zwischen 20 und 90 Euro zahlen. Damit liegt er in der Champagnerklasse. Da sich Aloe Vera noch nicht zu einem derartigen Kultgetränk entwickelt hat, steht also der Schluss nahe, das es zu anderen Zwecken als Genusszwecken verwendet wird. Die Hersteller freuts. Nirgendwo sind die Spannen so hoch wie im NEM-Markt.
Literatur
http://planeta.clix.pt/plantura/deutsch/aloe-deutsch.htm
Das Gel enthät natürlicherweise Aloine (in geringer Menge), ist also NICHT frei von Aloinen.
Zusatz: Über Herstellung und Anwendung von Aloe
Zum Thema Aloe schreibt das Nachschlagewerk "Hunnius - Pharmazeutisches Wörterbuch":
------------------------------------------------------------------------------- "Aloe: Succus Aloe inspissatus, Bärengalle; der bis zur Trockne eingedickte Saft der Blätter einiger Arten der Gattung Aloe, Fam. Liliaceae (bzw. Fam. Asphodelaceae). Man unterscheidet im allgemeinen zwischen Aloe lucida (mit glänzenden Bruchflächen), erhalten durch rasches Eindampfen des Saftes, und Aloe hepatica (leberfarben, matt), gewonnen durch langsames Eindampfen. Aloe ist von eigenartigem Geruch und von stark bitteren Geschmack, wenig löslich in Wasser v. 20°C, fast ohne Rückstand löslich in siedenden Wasser" -------------------------------------------------------------------------------
("Aloe lucida" und "Aloe hepatica" sind dabei lediglich Bezeichnungen für das Aussehen der Aloe-Rohwaren. Die aus "Aloe barbadensis MILLER" (= Aloe vera L.; im Mittelmeerraum und in der Karibik verbreitet) gewonnene "Curacao-Aloe" wird schonend getrocknet und im allg. als Hepatica-Ware angeboten - im Gegensatz zu der aus Aloe ferox MILLER (Afrika) gewonnenen "Kap-Aloe", die in Tiegeln über offenen Feuer getrocknet als Lucida-Ware angeboten wird.)
Auch die Monographieen des Arzneibuchs (Pharm. Eur. III) sprechen vom eingedickten "Pflanzensaft"!. Dies ist ebenfalls in den Lehrbüchern der pharm. Biologie und Heilpflanzenkompendien (z.B. W. Schaffner) zu lesen.
Daß Aloe plötzlich etwas ganz anderes sein soll, hörte ich erstmals im Internet - einem nicht sehr vertrauenswürdigen Medium.
Aloe auf das an Blättern anhaftende Blattharz zu beschränken ist Unsinn, zumindest wird dies nicht pharmazeutisch verwendet.
Wie auch auf den WHO-Seiten zu lesen ist, befinden sich die Aloine in und unterhalb der Blatthülle. Hier liegt wohl auch der Verarbeitungsunterschied. Die meisten Aloe-Vera-Vertreiber heben auf ihren Hompages die "Filetierung" der Blattstücke bei der Herstellung hervor. Auf diese weise werden die Aloine weitgehend abgetrennt, wie dies auch im WHO-Artikel zu lesen ist. Dennoch wird vielfach auf ein derartiges Verfahren verzichtet. Einige Anbieter preisen ihre Produkte als Ganzblatt-Präparate (z.B. www.aim-naturprodukte.com) oder als ausdrücklich aloinhaltig (z.B. www.interaloe.com) an - als Lebensmittel natürlich...
Die zahlreichen Publikationen über Aloe vera, die die WHO wiedergibt, spiegeln genau das wieder, was man auch im Pubmed findet: zahlreiche interessante Ergebnisse in in-vitro- und in Tierversuchen nach intravasculärer Applikation (insbesondere immunmodulatorische Effekte) einerseits - und nur vereinzelte positive Ergebnisse im Humanversuch, die sich dann auch fast nur auf dermatologische Anwendungen beschränken, andererseits.
Daß die Informationen über Nebenwirkungen respektive Giftigkeit der Aloe kein Geheimwissen sind, zeigt eine Web-Site über Pflanzen und Gärtnerei: http://www.desert-tropicals.com/Plants/Asphodelaceae/Aloe_vera.html
Dort heißt es wörtlich:
(Hervorhebungen von mir)
------------------------------------------------------------------------------- Medicinal Aloe Scientific Name: Aloe vera (L.)Burm.f. Synonym: Aloe barbadensis family: Asphodelaceae Recommended Temperature Zone: sunset: 8,9,12-27 USDA: 9-10 Frost Protection: Hardy to 23øF (-5øC) Sun Exposure: Full sun Origin: Cape Verde Islands, Canary Islands Growth Habits: Clumping rosettes, each about 8 inches in diameter (20 cm). Watering Needs: Drought resistant, but use moderate to regular water if you plan to use the plant for its gel. Propagation: Offsets The moist gel inside the Medicinal Aloe leaves is used to treat burns, including sunburns. Skin inflammation can occur in sensitive individuals. The gel is mildly toxic if ingested. -------------------------------------------------------------------------------
Die WHO hat im Internet Texte zu Medizin und Pharmazie, darunter auch über Heilpflanzen:
http://www.who.int/medicines/library/trm/medicinalplants/monograph_volume_one.shtml
Die Texte liegen als PDF-Files vor. (Eine Liste finden Sie hier)
In den "WHO monographs on selected medicinal plants" ist in "Volume 1":
Es ist notwendig, als Querverweis zu den Behauptungen der Verkäufer bestimmte Stellen zu markieren und zu kommentieren. Deshalb mußten die beiden Texte der WHO hier zu Beweiszwecken eingebunden werden (siehe hierzu insbesondere die unterstrichenen Passagen).
Die Texte weisen unmißverständlich hin auf
Wenn also jemand in einer Fernsehsendung als derjenige vorgestellt wird, "der auf der Erde am meisten über aloe vera weiß", dann sollte dieser Jemand diese Fakten kennen und auf diese Fakten hinweisen.
Wenn also in der Sendung "Fliege" ein Michael Peuser von Jürgen Fliege als derjenige vorgestellt wird, "der auf der Erde am meisten über aloe vera weiß", dann sollte dieser Michael Peuser diese Fakten kennen und auf diese Fakten hinweisen. Er tat es nicht.
Es ist unverantwortlich von Jürgen Fliege und von seiner Redaktion und von Michael Peuser, diese Informationen zu unterschlagen.
Original-URL: http://www.who.int/medicines/library/trm/medicinalplants/pdf/033to042.pdf
Aloe
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Aloe
Definition
Aloe is the dried juice of the leaves of Aloe vera (L.) Burm. f. or of A. ferox Mill. and its hybrids with A. africana Mill. and A. spicata Baker (Liliaceae) (1-6).
Synonyms
Aloe vera (L.) Burm. f.
In most formularies and reference books, Aloe barbadensis Mill. is regarded as the correct species name, and Aloe vera (L.) Burm. f. is considered a synonym.
However, according to the International Rules of Botanical Nomenclature, Aloe vera (L.) Burm. f. is the legitimate name for this species (8-10). The genus Aloe has also been placed taxonomically in a family called Aloeaceae.
Aloe ferox Mill.
Selected vernacular names
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Description
Aloe vera (L.) Burm. f.
Succulent, almost sessile perennial herb; leaves 30-50cm long and 10cm broad at the base; colour pea-green (when young spotted with white); bright yellow tubular flowers 25-35cm in length arranged in a slender loose spike; stamens frequently project beyond the perianth tube (12).
Aloe ferox Mill.
Arborescent perennial shrub with a single stem of 2-3m in height, crowned by a large rosette of numerous leaves which are glaucous, oval-lanceolate, 40- 60cm in length, thorny on the ridge and the edges; inflorescence an erect raceme 60 cm in height; flowers with perianth 2.5 cm in length, red, yellow, or orange (2).
Plant material of interest: dried juice
Solidified juice originating in the cells of the pericycle and adjacent leaf parenchyma, and flowing spontaneously from the cut leaf, allowed to dry with or without the aid of heat.
It is not to be confused with Aloe Vera Gel, which is the colourless mucilaginous gel obtained from the parenchymatous cells in the leaves of Aloe vera (L.) Burm. f. (13).
General appearance
Curacao or Barbados Aloe, derived from Aloe vera (L.) Burm. f.
The dried juice occurs in dark chocolate-brown usually opaque masses; fracture, dull waxy, uneven, and frequently conchoidal (2, 6).
Cape Aloe, derived from A. ferox Mill. and its hybrids with A. africana Mill. and A. spicata Baker
The dried juice occurs in dark brown or greenish brown glassy masses, often covered with a yellowish powder; in thin fragments it is transparent and exhibits a yellowish, reddish brown or greenish tinge; fracture, smooth, even, and glassy (2, 6).
Organoleptic properties
Aloe is marketed as opaque masses that range from reddish black to brownish black to dark brown in colour. Odour, characteristic and disagreeable; taste, somewhat sour, nauseating and very bitter (2, 7, 12).
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Microscopic characteristics
See -Powdered plant material below. Powdered plant material
Powdered aloes are yellowish brown to dark reddish brown. Microscopically, Cape Aloe appears as transparent brown or greenish brown irregular and angular fragments; Curacao Aloe shows fragments with numerous minute acicular crystals embedded in an amorphous matrix (1-3, 12, 14).
Geographical distribution
Native to southern and eastern Africa, and subsequently introduced into northern Africa, the Arabian peninsula, China, Gibraltar, the Mediterranean countries, and the West Indies (15). It is commercially cultivated in Aruba, Bonaire, Haiti, India, South Africa, the United States of America, and Venezuela (2, 7, 12, 14, 15).
General identity tests
Macroscopic and microscopic examinations (1-3, 7, 12, 14); solvent solubility (hot alcohol, boiling water, and ether) determination (2, 4-6); chemical reactions (1-6, 8, 12-14); and thin-layer chromatographic analysis employing barbaloin as the reference standard (4-7).
Purity tests
Microbiology
The test for Salmonella spp. in aloe products should be negative. The maximum acceptable limits of other microorganisms are as follows (16-18).
For preparation of decoction: aerobic bacteria -- not more than 10^7/g; fungi -- not more than 10^5/g; Escherichia coli -- not more than 10^2/g. Preparations for internal use: aerobic bacteria -- not more than 10^5/g or ml; fungi -- not more than 10^4/g or ml; enterobacteria and certain Gram-negative bacteria -- not more than 10^3/g or ml; Escherichia coli -- 0/g or ml.
Foreign organic matter
Adulterants: Aloe in commerce may sometimes be adulterated with black catechu, pieces of iron, and stones. These can be detected by examining alcohol-soluble extracts under ultraviolet light which gives a deep brown colour with aloe and a black colour with catechu (14).
Total ash
Not more than 2% (3-5).
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Water-soluble extracts
Not less than 50% (1, 2, 14).
Alcohol-insoluble extracts
Not more than 10% (1-3, 14).
Moisture
Not more than 10% for Cape Aloe (6), and not more than 12% for Curacao or Barbados Aloe (2-6, 14).
Pesticide residues
To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin for Aloe is not more than 0.05 mg/kg (18). For other pesticides, see the WHO guidelines on quality control methods for medicinal plants (16) and guidelines for predicting dietary intake of pesticide residues (19).
Heavy metals
Recommended lead and cadmium levels are not more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (16).
Radioactive residues
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (16).
Other tests
Acid-insoluble ash and chemical tests to be established in accordance with national requirements.
Chemical assays
Thin-layer chromatography and microchemical analyses are employed for the qualitative analysis for the presence of anthracene glycosides (1-7, 12, 14). Quantitative analysis of total anthracene glycosides, calculated as barbaloin, is performed by spectrophotometry (4, 5).
Curacao or Barbados Aloe, derived from Aloe vera (L.) Burm. f.
Contains not less than 28% of hydroxyanthracene derivatives, expressed as
barbaloin (4-6).
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Cape Aloe, derived from A. ferox Miller and its hybrids with
A. africana Mill. and A. spicata Baker
Contains not less than 18% of hydroxyanthracene derivatives, expressed as
barbaloin (4, 5).
Major chemical constituents
Aloe contains as its major and active principles hydroxyanthrone derivatives, mainly of the aloe-emodin-anthrone 10-C-glucoside type. The major constituent is known as barbaloin (aloin) (15-40%) (8, 13). It also contains hydroxyaloin (about 3%). Barbaloin ( aloin) is in fact a mixture of aloin A (10S) [1] and B (10R) [2]. A. ferox also contains aloinoside A [3] and B [4]. Aloin A and B interconvert through the anthranol form as do aloinoside A and B (13).
Dosage forms
Powdered, dried juice and preparations thereof for oral use.
Medicinal uses
Uses supported by clinical data
Short-term treatment of occasional constipation (2, 12, 13, 15).
Uses described in pharmacopoeias and in traditional systems of medicine
None.
Uses described in folk medicine, not supported by experimental or clinical data
Treatment of seborrhoeic dermatitis, peptic ulcers, tuberculosis, and fungal infections, and for reduction of blood sugar (glucose) levels (11, 20).
[ --- hier finden Sie im Original Strukturformeln ---]
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Pharmacology
Experimental pharmacology
As shown for senna, Aloe's mechanism of action is twofold. It stimulates colonic motility, augmenting propulsion and accelerating colonic transit, which reduces fluid absorption from the faecal mass. It also increases paracellular permeability across the colonic mucosa probably owing to an inhibition of Na+, K+-adenosine triphosphatase or to an inhibition of chloride channels (8, 21, 22), which results in an increase in the water content in the large intestine (21).
Clinical pharmacology
The laxative effects of Aloe are due primarily to the 1, 8-dihydroxyanthracene glycosides, aloin A and B (formerly designated barbaloin) (23, 24). After oral administration aloin A and B, which are not absorbed in the upper intestine, are hydrolysed in the colon by intestinal bacteria and then reduced to the active metabolites (the main active metabolite is aloe-emodin-9-anthrone) (25, 26), which like senna acts as a stimulant and irritant to the gastrointestinal tract (27).
The laxative effect of Aloe is not generally observed before 6 hours after oral administration, and sometimes not until 24 or more hours after.
Toxicity
The major symptoms of overdose are griping and severe diarrhoea with consequent losses of fluid and electrolytes. Treatment should be supportive with generous amounts of fluid. Electrolytes, particularly potassium, should be monitored in all recipients, especially in children and the elderly (28).
Contraindications
As with other stimulant laxatives, products containing Aloe should not be used in patients with intestinal obstruction or stenosis, atony, severe dehydration with electrolyte depletion, or chronic constipation (28). Aloe should not be administered to patients with inflammatory intestinal diseases, such as appendicitis, Crohn disease, ulcerative colitis, irritable bowel syndrome, or diverticulitis, or to children under 10 years of age. Aloe should not be used during pregnancy or lactation except under medical supervision after evaluating benefits and risks. Aloe is also contraindicated in patients with cramps, colic, haemorrhoids, nephritis, or any undiagnosed abdominal symptoms such as pain, nausea, or vomiting (28, 29).
Warnings
Aloe-containing products should be used only if no effect can be obtained through a change of diet or use of bulk-forming products. Stimulant laxative products should not be used when abdominal pain, nausea, or vomiting are present. Rectal bleeding or failure to have a bowel movement within 24 hours.
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after use of a laxative may indicate a serious condition. Chronic use may cause dependence and need for increased dosages, disturbances of water and electrolyte balance (e.g. hypokalaemia), and an atonic colon with impaired function (28).
The use of stimulant laxatives for more than 2 weeks requires medical supervision.
Chronic abuse with diarrhoea and consequent fluid and electrolyte losses (mainly hypokalaemia) may cause albuminuria and haematuria, and may result in cardiac and neuromuscular dysfunction, the latter particularly in the case of concomitant use of cardiac glycosides (digoxin), diuretics, corticosteroids, or liquorice root (see Precautions below).
Precautions
General
Laxatives containing anthraquinone glycosides should not be used continuously for longer than 1-2 weeks, owing to the danger of electrolyte imbalance.
Drug interactions
Decreased intestinal transit time may reduce absorption of orally administered drugs (30).
Existing hypokalaemia resulting from long-term laxative abuse can potentiate the effects of cardiotonic glycosides (digitalis, strophanthus) and anti-arrhythmic drugs such as quinidine (30). The induction of hypokalaemia by drugs such as thiazide diuretics, adrenocorticosteroids, and liquorice root may be enhanced, and electrolyte imbalance may be aggravated (31).
Drug and laboratory test interactions
Standard methods may not detect anthranoid metabolites, so measurements of faecal excretion may not be reliable (26). Urinary excretion of certain anthranoid metabolites may discolour the urine, which is not clinically relevant but which may cause false positive results for urinary urobilinogen, and for estrogens when measured by the Kober procedure (30).
Carcinogenesis, mutagenesis, impairment of fertility
Data on the carcinogenicity of Aloe are not available. While chronic abuse of anthranoid-containing laxatives was hypothesized to play a role in colorectal cancer, no causal relationship between anthranoid laxative abuse and colorectal cancer has been demonstrated (32-35).
In vitro (gene mutation and chromosome aberration tests) and in vivo (micro-nucleus test in murine bone marrow) genotoxicity studies, as well as human and animal pharmacokinetic data, indicate no genotoxic risk from Cape Aloe (36-38).
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Pregnancy: teratogenic effects
No teratogenic or fetotoxic effects were seen in rats after oral treatment with aloe extract (up to 1000 mg/kg) or aloin A (up to 200 mg/kg) (39).
Pregnancy: non-teratogenic effects
Aloe should not be used during pregnancy except under medical supervision after benefits and risks have been evaluated (40).
Nursing mothers
Anthranoid metabolites appear in breast milk. Aloe should not be used during lactation except under medical supervision, as there are insufficient data available to assess the potential for pharmacological effects in the breast-fed infant (30, 40).
Paediatric use
Oral use of Aloe in children under 10 years old is contraindicated.
Adverse reactions
Abdominal spasms and pain may occur after even a single dose. Overdose can lead to colicky abdominal spasms and pain, as well as the formation of thin, watery stools (28).
Chronic abuse of anthraquinone stimulant laxatives can lead to hepatitis (41).
Long-term laxative abuse may lead to electrolyte disturbances (hypokalaemia, hypocalcaemia), metabolic acidosis, malabsorption, weight loss, albuminuria, and haematuria (30, 42, 43).
Weakness and orthostatic hypotension may be exacerbated in elderly patients when stimulant laxatives are repeatedly used (31).
Secondary aldosteronism may occur owing to renal tubular damage after aggravated use. Steatorrhoea and protein-losing gastroenteropathy with hypoalbuminaemia have also been observed, as have excessive excretion of calcium in the stools and osteomalacia of the vertebral column (44, 45).
Melanotic pigmentation of the colonic mucosa (pseudo-melanosis coli) has been observed in individuals taking anthraquinone laxatives for extended time periods (29, 42). The pigmentation is clinically harmless and usually reversible within 4 to 12 months after the drug is discontinued (29, 42).
Conflicting data exist on other toxic effects such as intestinal-neuronal damage after long-term use (42, 46).
Posology
The correct individual dose is the smallest amount required to produce a soft-formed stool (26).
As a laxative for adults and children over 10 years old, 0.04-0.11 g (Curacao or Barbados Aloe) or 0.06-0.17 g (Cape Aloe) of the dried juice (6, 14), corresponding to 10-30mg hydroxyanthraquinones per day, or 0.1 g as a single dose in the evening.
Aloe
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References
Original-URL: http://www.who.int/medicines/library/trm/medicinalplants/pdf/043to049.pdf
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Aloe Vera Gel
Definition
Aloe Vera Gel is the colourless mucilaginous gel obtained from the parenchy-matous cells in the fresh leaves of Aloe vera (L) Burm. f. (Liliaceae) (1, 2). Synonyms Aloe barbadensis Mill., Aloe chinensis Bak., A. elongata Murray, A. indica Royle, A. officinalis Forsk., A. perfoliata L., A. rubescens DC, A. vera L. var. littoralis König ex Bak., A. vera L. var. chinensis Berger, A. vulgaris Lam. (2-5). Most formularies and reference books regard Aloe barbadensis Mill. as the correct species name, and Aloe vera (L.) Burm. f. as a synonym. However, according to the International Rules of Botanical Nomenclature, Aloe vera (L.) Burm. f. is the legitimate name for this species (2-4). The genus Aloe has also been placed taxonomically in a family called Aloeaceae.
Selected vernacular names
Aloe vera gel, aloe gel.
Description
Succulent, almost sessile perennial herb; leaves 30-50 cm long and 10 cm broad at the base; colour pea-green (when young spotted with white); bright yellow tubular flowers 25-35 cm in length arranged in a slender loose spike; stamens frequently project beyond the perianth tube (6).
Plant material of interest: liquid gel from the fresh leaf
Aloe Vera Gel is not to be confused with the juice, which is the bitter yellow exudate originating from the bundle sheath cells of the leaf. The drug Aloe consists of the dried juice, as defined on page 33.
General appearance
The gel is a viscous, colourless, transparent liquid.
Organoleptic properties
Viscous, colourless, odourless, taste slightly bitter.
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Microscopic characteristics
Not applicable.
Geographical distribution
Probably native to north Africa along the upper Nile in the Sudan, and subsequently introduced and naturalized in the Mediterranean region, most of the tropics and warmer areas of the world, including Asia, the Bahamas, Central America, Mexico, the southern United States of America, south-east Asia, and the West Indies (2).
General identity tests
To be established in accordance with national requirements.
Purity tests
Microbiology
The test for Salmonella spp. in Aloe Vera Gel should be negative. Acceptable maximum limits of other microorganisms are as follows (7-9).
For external use: aerobic bacteria -- not more than 10^2/ml; fungi -- not more than 10^2/ml; entero-bacteria and certain Gram-negative bacteria -- not more than 10^1/ml; Staphylo-coccus spp. -- 0/ml. (Not used internally.)
Moisture
Contains 98.5% water (10).
Pesticide residues
To be established in accordance with national requirements. For guidance, see WHO guidelines on quality control methods for medicinal plants (7) and guidelines on predicting dietary intake of pesticide residues (11).
Heavy metals
Recommended lead and cadmium levels are not more than 10 and 0.3mg/kg, respectively, in the final dosage form (7).
Radioactive residues
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (7).
Other tests
Chemical tests for Aloe Vera Gel and tests for total ash, acid-insoluble ash, alcohol-soluble residue, foreign organic matter, and water-soluble extracts to be established in accordance with national requirements.
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Chemical assays
Carbohydrates (0.3%) (12), water (98.5%) (10). Polysaccharide composition analysis by gas-liquid chromatography (13).
Major chemical constituents
Aloe Vera Gel consists primarily of water and polysaccharides (pectins, hemi-celluloses, glucomannan, acemannan, and mannose derivatives). It also contains amino acids, lipids, sterols (lupeol, campesterol, and -sitosterol), tannins, and enzymes (1). Mannose 6-phosphate is a major sugar component (14).
Dosage forms
The clear mucilaginous gel. At present no commercial preparation has been proved to be stable. Because many of the active ingredients in the gel appear to deteriorate on storage, the use of fresh gel is recommended. Preparation of fresh gel: harvest leaves and wash them with water and a mild chlorine solution.
Remove the outer layers of the leaf including the pericyclic cells, leaving a "fillet" of gel. Care should be taken not to tear the green rind which can contaminate the fillet with leaf exudate. The gel may be stabilized by pasteurization at 75-80°C for less than 3 minutes. Higher temperatures held for longer times may alter the chemical composition of the gel (2).
Medicinal uses
Uses supported by clinical data
None.
Uses described in pharmacopoeias and in traditional systems of medicine
Aloe Vera Gel is widely used for the external treatment of minor wounds and inflammatory skin disorders (1, 14-17). The gel is used in the treatment of minor skin irritations, including burns, bruises, and abrasions (1, 14, 18). The gel is further used in the cosmetics industry as a hydrating ingredient in liquids, creams, sun lotions, shaving creams, lip balms, healing ointments, and face packs (1).
Aloe Vera Gel has been traditionally used as a natural remedy for burns (18, 19). Aloe Vera Gel has been effectively used in the treatment of first- and second-degree thermal burns and radiation burns. Both thermal and radiation burns healed faster with less necrosis when treated with preparations containing Aloe Vera Gel (18, 19). In most cases the gel must be freshly prepared because of its sensitivity to enzymatic, oxidative, or microbial degradation.
Aloe Vera Gel is not approved as an internal medication, and internal adminis-tration of the gel has not been shown to exert any consistent therapeutic effect.
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Uses described in folk medicine, not supported by experimental or clinical data
The treatment of acne, haemorrhoids, psoriasis, anaemia, glaucoma, petit ulcer, tuberculosis, blindness, seborrhoeic dermatitis, and fungal infections (2, 6, 19).
Pharmacology
Wound healing
Clinical investigations suggest that Aloe Vera Gel preparations accelerate wound healing (14, 18). In vivo studies have demonstrated that Aloe Vera Gel promotes wound healing by directly stimulating the activity of macrophages and fibroblasts (14). Fibroblast activation by Aloe Vera Gel has been reported to increase both collagen and proteoglycan synthesis, thereby promoting tissue repair (14). Some of the active principles appear to be polysaccharides composed of several monosaccharides, predominantly mannose. It has been suggested that mannose 6-phosphate, the principal sugar component of Aloe Vera Gel, may be partly responsible for the wound healing properties of the gel (14).
Mannose 6-phosphate can bind to the growth factor receptors on the surface of the fibroblasts and thereby enhance their activity (14, 15).
Furthermore, acemannan, a complex carbohydrate isolated from Aloe leaves, has been shown to accelerate wound healing and reduce radiation-induced skin reactions (20, 21).
The mechanism of action of acemannan appears to be twofold.
First, acemannan is a potent macrophage-activating agent and therefore may stimulate the release of fibrogenic cytokines (21, 22). Second, growth factors may directly bind to acemannan, promoting their stability and prolonging their stimulation of granulation tissue (20).
The therapeutic effects of Aloe Vera Gel also include prevention of progressive dermal ischaemia caused by burns, frostbite, electrical injury and intra-arterial drug abuse. In vivo analysis of these injuries demonstrates that Aloe Vera Gel acts as an inhibitor of thromboxane A2, a mediator of progressive tissue damage (14, 17). Several other mechanisms have been proposed to explain the activity of Aloe Vera Gel, including stimulation of the complement linked to polysaccharides, as well as the hydrating, insulating, and protective properties of the gel (1).
Because many of the active ingredients appear to deteriorate on storage, the use of fresh gel is recommended. Studies of the growth of normal human cells in vitro demonstrated that cell growth and attachment were promoted by exposure to fresh Aloe vera leaves, whereas a stabilized Aloe Vera Gel preparation was shown to be cytotoxic to both normal and tumour cells. The cytotoxic effects of the stabilized gel were thought to be due to the addition of other substances to the gel during processing (23).
Anti-inflammatory
The anti-inflammatory activity of Aloe Vera Gel has been revealed by a number of in vitro and in vivo studies (14, 17, 24, 25). Fresh Aloe Vera Gel significantly
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reduced acute inflammation in rats (carrageenin-induced paw oedema), although no effect on chronic inflammation was observed (25). Aloe Vera Gel appears to exert its anti-inflammatory activity through bradykinase activity (24) and thromboxane B2 and prostaglandin F2 inhibition (18, 26). Furthermore, three plant sterols in Aloe Vera Gel reduced inflammation by up to 37% in croton oil-induced oedema in mice (15). Lupeol, one of the sterol compounds found in Aloe vera, was the most active and reduced inflammation in a dose-dependent manner (15). These data suggest that specific plant sterols may also contribute to the anti-inflammatory activity of Aloe Vera Gel.
Burn treatment
Aloe Vera Gel has been used for the treatment of radiation burns (27-30).
Healing of radiation ulcers was observed in two patients treated with Aloe vera cream (27), although the fresh gel was more effective than the cream (29, 30).
Complete healing was observed, after treatment with fresh Aloe Vera Gel, in two patients with radiation burns (30). Twenty-seven patients with partial-thickness burns were treated with Aloe Vera Gel in a placebo-controlled study (31). The Aloe Vera Gel-treated lesions healed faster (11.8 days) than the burns treated with petroleum jelly gauze (18.2 days), a difference that is statistically significant (t-test, P 0.002).
Contraindications
Aloe Vera Gel is contraindicated in cases of known allergy to plants in the Liliaceae.
Warnings
No information available.
Precautions
No information available concerning general precautions, or precautions dealing with carcinogenesis, mutagenesis, impairment of fertility; drug and laboratory test interactions; drug interactions; nursing mothers; paediatric use; or teratogenic or non-teratogenic effects on pregnancy.
Adverse reactions
There have been a few reports of contact dermatitis and burning skin sensations following topical applications of Aloe Vera Gel to dermabraded skin (18, 32). These reactions appeared to be associated with anthraquinone contaminants in this preparation (33). A case of disseminated dermatitis has been reportedfollowing application of Aloe Vera Gel to a patient with stasis dermatitis (34).
An acute bullous allergic reaction and contact urticaria have also been reported to result from the use of Aloe Vera Gel (35).
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Posology
Fresh gel or preparations containing 10-70% fresh gel.
References
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