Symphytum officinale, commonly known as comfrey, is an evergreen herb belonging to the borage family (Boraginaceae). Comfrey is a native herb of Eurasia, and is often escaped or adventive in waste places (Gleason & Cronquist 1963). In the United States, S. officinale is found in the east, midwest, and west, and more sparingly in the southern states (Benson 1979).
S. officinale is used as a vegetable as well as an herbal remedy. Comfrey is also widely consumed by humans as a medicinal herb and is used as a therapeutic treatment for many illnesses. Preparations of the roots and leaves are available in a capsule form and as an herbal infusion or tea (Winship 1991, Yeong et. al. 1990). Traditionally, it has been used as a 'demulcent in chronic catarrhs, and certain mucous membrane affections of the gastrointestinal tract', and as a tonic (Winship 1991). In the United Kingdom, herbalists use S. officinale as a demulcent, an antihaemorrhagic, an antirheumatic, and an anti-inflammatory agent. The dried roots and leaves and the fresh leaves have both oral and topical uses. The traditional uses for internal consumption include gastric and duodenal ulcer, haematemesis, colitis, rheumatic pain, and arthritis. The topical applications include ulcers, bruises, sprains, athlete's foot, crural ulcers, wounds, fractures, and herniae, and chronic varicose ulceration appears to be a specific indication. (Winship 1991) Many members belonging to the borage family, including S. officinale, are found to contain the chemical constituent allantoin, which promotes healing. Comfrey contains about 0.8% in the root and 0.4% in the leaf preparation of this allantoin (Winship 1991, Benson 1979).
Like other members the Boraginaceae, the roots of comfrey contain pyrrolizidine alkaloids, which are hepatotoxic and carcinogenic agents (Winship 1991). They may cause veno-occlusive disease of the liver, occasionally with fatal results. Due to the presence of these heptatoxic pyrrolizidine alkaloids and the widespread use of this plant as a herbal tea, the toxicity of S. officinale became of increasing concern (Betz et. al. 1994, Winship 1991). A method for the extraction and solid-phase concentration and capillary gas chromatographic determination of these alkaloids and their N-oxides in botanical materials has been developed and was applied to eleven comfrey-containing products purchased from retail health-food outlets in Washington, DC. Nine of the eleven products were found to contain measurable quantities of one or more of the alkaloids. Products containing comfrey leaf in combination with one or more other ingredients naturally were found to contain the lowest alkaloid levels; as where highest levels were found in bulk comfrey roots and leaves (Betz et. al. 1994).
S. officinale contains a range of pyrrolizidine alkaloids and the corresponding N-oxides of differing biological effects (Mattocks 1980). While the major determinates of the toxicity of pyrrolizidine alkaloids are free base or N-oxide, with unsaturation at C2 and esterification at C7 or C9, the exact nature of the structure and activity relationships of the alkaloids are unknown (Couet et. al. 1996).
New procedures are described for converting unsaturated pyrrolizidine alkaloids to chemically reactive pyrrolic esters, which are probable primary toxic metabolites formed from these alkaloids in vivo. Preparations of dehydro-necines, including dehydroretronecine (DRH) are also described. Dehydrocrotanecine, and four new dehydro-alkaloids, are described for the first time. The methods give superior yields to earlier procedures, do not require a high degree of chemical expertise, and are particularly suitable for making small amounts of compounds for toxicological experiments (Mattocks et. al. 1989)
A case report described one patient with hepatic veno-occlusive disease and severe portal hypertension, who subsequently died from liver failure after injesting young comfrey leaves. The patient had been on a predominantly vegetarian diet and, prior to his illness, took comfrey leaves which are known to contain hepatotoxic pyrrolizidine alkaloids. Light microscopy and hepatic angiography showed occlusion of sublobular veins and small venous radicles of the liver, associated with widespead haemorrhagic necrosis of hepatocytes. The ingestion of significant quantities of young comfrey leaves just prior to the onset of symptoms, the histology which is compatible with pyrrolizidine toxicity, and the exclusion of other know causes of veno-occlusive disease is all point to the relationship between this patients's comfrey ingestion and the subsequent illness (Yeong et. al. 1990).
Aqueous solutions of three alkaloids fractions obtained from infusions of the comfrey root were tested for their antimitotic and mutagenic activity in meristematic cells of the lateral roots of Vicia faba. Lasiocarpine, a proven carcinogen, served as a possible control. Mutagenic effects were induced by lasiocarpine, by the alkaloid fraction I and by diluted infusions from Radix Symphyti. These tested solutions showed the mutagenic effects on the extracts of S. officinale (Furmanowa et. al. 1983)
The Ames test, which tests bacteria to determine if it produces mutations, was used to evaluate acetone extracts from S. officinale for mutagenic activity, using Salmonella and mammalian-microsome mutagenicity test (Ames) utilizing tester strains TA98 and TA100 and in the presence and absence of induced rat liver microsomes. Extracts from some plants produced only negative responses. However, extracts from S. officinale produced toxic responses that were abolished in the presence of the microsomal bioactivation system.
Anti-inflammatory tests were performed on a group of plant extracts, including S. officinale, by using Wistar albino rats. An inflammation was induced via the simultaneous injection of carageenan and prostaglandin E1 in order to evaluate the antiinflammatory activity of freeze dried plant extracts. Shipochliev et.al. (1981) found that the inflammatory effect of caraginan was strongly enhanced, and accompanied by the rapid and prolific white blood cell extravasates. The freeze-dried extracts of comfrey did not inhibit the inflammation, however, it surpessed the leukocyte infiltration at the third and forth hours of induced inflammation (Shipochliev et. al. 1981).
An alkaloid extract of S. officinale was investigated for its chromosome-damaging effect in human lymphocytes in vitro. In concentrations 1.4 or 14 micrograms/ml the alkaloids had no effect; in concentrations of 140 or 1400 micrograms/ml the alkaloids induced sister chromatid exchanges as well as chromosome aberrations (Behninger et. al. 1989).
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