Symphytum Research Articles

Efficacy of a comfrey root extract ointment in the treatment of painful osteoarthritis

Efficacy of a comfrey root extract ointment in the treatment of painful osteoarthritis

Analysis of gene expression changes in relation to toxicity and tumorigenesis in the livers of Big Blue transgenic rats fed comfrey (Symphytum officinale)

BackgroundComfrey is consumed by humans as a vegetable and a tea, and has been used as an herbal medicine for more than 2000 years. Comfrey, however, is hepatotoxic in livestock and humans and carcinogenic in experimental animals. Our previous study suggested that comfrey induces liver tumors by a genotoxic mechanism and that the pyrrolizidine alkaloids in the plant are responsible for mutation induction and tumor initiation in rat liver.ResultsIn this study, we identified comfrey-induced gene expression profile in the livers of rats. Groups of 6 male transgenic Big Blue rats were fed a basal diet and a diet containing 8% comfrey roots, a dose that resulted in liver tumors in a previous carcinogenicity bioassay. The animals were treated for 12 weeks and sacrificed one day after the final treatment. We used a rat microarray containing 26,857 genes to perform genome-wide gene expression studies. Dietary comfrey resulted in marked changes in liver gene expression, as well as in significant decreases in the body weight and increases in liver mutant frequency. When a two-fold cutoff value and a P-value less than 0.01 were selected, 2,726 genes were identified as differentially expressed in comfrey-fed rats compared to control animals. Among these genes, there were 1,617 genes associated by Ingenuity Pathway Analysis with particular functions, and the differentially expressed genes in comfrey-fed rat livers were involved in metabolism, injury of endothelial cells, and liver injury and abnormalities, including liver fibrosis and cancer development.ConclusionThe gene expression profile provides us a better understanding of underlying mechanisms for comfrey-induced hepatic toxicity. Integration of gene expression changes with known pathological changes can be used to formulate a mechanistic scheme for comfrey-induced liver toxicity and tumorigenesis.

Formation of DHP-derived DNA adducts in vivo from dietary supplements and Chinese herbal plant extracts containing carcinogenic pyrrolizidine alkaloids

We recently determined that the metabolism of a series of tumorigenic pyrrolizidine alkaloids resulted in the formation of a set of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts. These DHP-derived DNA adducts have been proposed as potential biomarkers of pyrrolizidine alkaloid tumorigenicity, as well as pyrrolizidine alkaloid exposure. In this paper, we report that DHP-derived DNA adducts are formed in the liver of female F344 rats, gavaged with three dietary supplements (comfrey root extract, comfrey compound oil, and coltsfoot root extract), or an extract of a Chinese herbal plant, flos farfara (Kuan Tong Hua).

Comparison of local Symphytum officinale L. (comfrey) root extract and diclofenac for sprained ankles

Focus on Alternative and Complementary TherapiesVolume 11, Issue 1 p. 21-22 Comparison of local Symphytum officinale L. (comfrey) root extract and diclofenac for sprained ankles First published: 14 June 2010 https://doi.org/10.1211/fact.11.1.0007Read the full textAbout ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume11, Issue1March 2006Pages 21-22 RelatedInformation

Efficacy of a Comfrey root extract ointment in comparison to a Diclo-fenac gel in the treatment of ankle distortions: Results of an observer-blind, randomized, multicenter study

In the treatment of minor blunt injuries several topical drugs are known to have anti-inflammatory and analgesic properties. They represent, however, two fundamentally different major pharmacological therapy approaches: the "chemical-synthetical" and the "phytotherapeutical" approach. The main objective of this trial (CODEC_2004) was to compare the efficacy and tolerability of an ointment of Comfrey extract (Extr. Rad. Symphyti) with that of a Diclofenac gel in the treatment of acute unilateral ankle sprain (distortion). In a single-blind, controlled, randomized, parallel-group, multicenter and confirmatory clinical trial outpatients with acute unilateral ankle sprains (n=164, mean age 29.0 years, 47.6% female) received either a 6 cm long ointment layer of Kytta-Salbe f (Comfrey extract) (n=82) or of Diclofenac gel containing 1.16 g of diclofenac diethylamine salt (n=82) for 7 +/- 1 days, four times a day. Primary variable was the area-under-the-curve (AUC) of the pain reaction to pressure on the injured area measured by a calibrated caliper (tonometer). Secondary variables were the circumference of the joint (swelling; figure-of-eight method), the individual spontaneous pain sensation at rest and at movement according to a Visual Analogue Scale (VAS), the judgment of impaired movements of the injured joint by the method of "neutral-zero", consumption of rescue medication (paracetamol), as well as the global efficacy evaluation and the global assessment of tolerability (both by physician and patient, 4 ranks). In this study the primary variable was also to be validated prospectively. It was confirmatorily shown that Comfrey extract is non-inferior to diclofenac. The 95% confidence interval for the AUC (Comfrey extract minus Diclofenac gel) was 19.01-103.09h*N/cm2 and was completely above the margin of non-inferiority. Moreover, the results of the primary and secondary variables indicate that Comfrey extract may be superior to Diclofenac gel.

A Rapid Cleanup Method for the Isolation and Concentration of Pyrrolizidine Alkaloids in Comfrey Root

Preparations from comfrey (Symphytum officinale and S. x uplandicum) root and leaf contain varying levels of the hepatotoxic pyrrolizidine alkaloids (PAs). Reference compounds for comfrey are not commercially available, and there is currently no rapid extraction or analytical method capable of determining low levels in raw materials or as adulterants in commercially available extracts. A solid-phase extraction (SPE) method was developed using an Ergosil cleanup column that specifically binds the PAs. With this method, powdered comfrey root was extracted by sonication and shaking with basic chloroform. The extract was applied to the cleanup column under vacuum, washed with 2 mL acetone-chloroform (8 + 2, v/v) followed by 2 mL petroleum ether to remove excess chloroform. The column was dried under vacuum, and the PAs were eluted with 2 successive 1 mL aliquots methanol. Percent recoveries of the PAs following Ergosil SPE had an overall average of 96.8%, with RSD of 3.8% over a range of 1.0 to 25.0 g extracted in 100 mL. Average precision of the method (n = 3 over 4 extraction concentrations) gave an overall RSD of 6.0% for the 5 alkaloids, with a range of 0.8% (5 g in 100 mL) to 11.2% (25 g in 100 mL). Recovery optimization testing showed that 1.0 g comfrey root extracted in 100 mL yielded the greatest recovery (% dry weight) of the PAs, with an extraction efficiency and accuracy of 94.2%, and RSD of 1.7% (n = 9). The unique properties of the Ergosil cleanup column provide rapid sample cleanup, volume reduction, and concentration of PAs from comfrey extracts, and allow the eluant to be analyzed directly by traditional chromatographic methods.

Efficacy and tolerance of a comfrey root extract (Extr. Rad. Symphyti) in the treatment of ankle distorsions: results of a multicenter, randomized, placebo-controlled, double-blind study

Comfrey (Symphytum officinale L.) is a medicinal plant with anti-inflammatory, analgesic and tissue regenerating properties. In a double-blind, multicenter, randomized, placebo-controlled, group comparison study on patients suffering from unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four treatments per day for 8 days) was confirmed decisively. Compared to placebo, the active treatment was clearly superior regarding the reduction of pain (tonometric measurement, p<0.0001, as the primary efficacy variable) and ankle edema (figure-of-eight method, p = 0.0001). Statistically significant differences between active treatment and placebo could also be shown for ankle mobility (neutral zero method), and global efficacy. Under active treatment, no adverse drug reactions were reported. The good local and global tolerance of the trial medication could also be confirmed. The study results are consistent with the known pre-clinical and clinical data concerning comfrey.

Simultaneous analysis of hepatotoxic pyrrolizidine alkaloids and N-oxides in comfrey root by LC-ion trap mass spectrometry.

The purpose of the current study was to develop a LC-MS(n) method for the analysis of pyrrolizidine alkaloids (PAs) in comfrey. Published data presents an extensive list of PAs and their N-oxides present in comfrey. However, standards are not commercially available for any of the PAs typically present in comfrey. Those PAs that are not stereoisomers were readily resolved on a C(18) column using a water-acetonitrile gradient as the mobile phase. The use of a selective technique, LC-MS/MS, allowed us to identify groups of PAs and their N-oxides, as well as identify the number of PAs present in each group, including those that were not completely resolved chromatographically.

Comfrey root and bone healing

Comfrey root and bone healing

Application of Gas Chromatography/Matrix Isolation/Fourier Transform Infrared Spectroscopy to the Identification of Pyrrolizidine Alkaloids from Comfrey Root (Symphytum officinale L.)

Abstract This paper demonstrates that pyrrolizidine alkaloids (PAs) extracted from comfrey root grown in Washington State (USA) can be identified by gas chromatography/matrix isolation/Fourier transform infrared (GC/MI/FTIR) spectroscopy. Infrared spectral bands observed in the fingerprint region were unique even for closely related structures. The identities of the 4 major components, intermedine, lycopsamine, 7-acetylintermedine, and 7-acetylly-copsamine, were confirmed by comparison with standards. Confirmation was also obtained by using the established techniques of electron ionization and positive ion chemical ionization gas chro-matography/mass spectrometry. The infrared spectra observed for the components of the root extract were consistent with known structures of specific PAs. The identities of the minor components, sym-phytine and its isomers symlandine and/or sym-viridine, in the same extract were not confirmed.

Determination of Pyrrolizidine Alkaloids in Commercial Comfrey Products

The presence of hepatotoxic pyrrolizidine alkaloids in comfrey (Symphytumsp.) and the widespread use of decoctions of this plant as a beverage (herbal tea) are of increasing concern. A method for the extraction and solid‐phase concentration and capillary gas chromatographic determination of these alkaloids and theirN‐oxides in botanical materials has been developed and was applied to eleven comfrey‐containing products purchased from retail health‐food outlets in the Washington, DC, area during May‐June 1989. Nine of the 11 products were found to contain measurable quantities of one or more of the alkaloids, in ranges from 0.1 to 400.0 ppm. Products containing comfrey leaf in combination with one or more other ingredients were found to contain the lowest alkaloid levels. Highest levels were found in bulk comfrey root, followed by bulk comfrey leaf. The species of the bulk material was verified by thin‐layer chromatography and other means.

Echimidine Content of Commercial Comfrey (Symphytumspp.-Boraginaceae)

The pyrrolizidine alkaloid (PA) content of 13 commercial comfrey products sold in Canada was examined following an increased health concern about the consumption of PA-containing plant material, and particularly comfrey, the use of which had been linked to a number of cases of human poisoning during the last decade. The samples were purchased so as to be representative of the variety of sources, shapes and forms of the commercially available products. Total PA content of comfrey root samples, determined by 1H-NMR spectroscopy, has indicated significant variation both quantitatively and qualitatively. The occurrence of echimidine, probably the most toxic PA of Symphytum spp., has been evaluated by reverse-phase HPLC (RP-HPLC), TLC, and GC-MS. Echimidine was detected in 9 of the 13 samples analyzed, and was noted to be the major PA constituent of 1 root preparation-approximately 85 percent Symphytum as measured by RP-HPLC. Leaf preparations generally contained lower levels of echimidine, detected only by GC-MS, associated with lower overall quantities of extract. Of the 6 preparations identified on the package label as being derived from the species Symphytum officinale, 3 were observed to contain echimidine at varying levels, likely an indication of inaccurate species designation since substantial echimidine content is usually indicative of Symphytum officinale hybridization.

COMFREY HERB TEA AND HEPATIC VENO-OCCLUSIVE DISEASE

COMFREY HERB TEA AND HEPATIC VENO-OCCLUSIVE DISEASE

Hepatic Venocclusive Disease Associated With the Consumption of Pyrrolizidine Containing Dietary Supplements

Venocclusive disease, a form of Budd-Chiari syndrome, was diagnosed in a 49-yr-old woman. The patient had portal hypertension associated with obliteration of the smaller hepatic venules. A liver biopsy specimen showed centrilobular necrosis and congestion. Analysis of food supplements the woman regularly consumed showed the presence of pyrrolizidine alkaloids. The major source was a powder purporting to contain ground comfrey root (Symphytum sp). We calculated that during the 6 mo before the woman was hospitalized, she had consumed a minimum of 85 mg of pyrrolizidine alkaloids (15 micrograms/kg body wt X day). The clinical and analytic findings were consistent with chronic pyrrolizidine intoxication, indicating that low-level, chronic exposure to such alkaloids can cause venocclusive disease.

The alkaloids of Symphytum × uplandicum (Russian comfrey)

Eight pyrrolizidine alkaloids have been identified in the leaves of Symphytum × uplandicum Nyman (Russian comfrey). They are echimidine (1), symphytine (2), lycopsamine (3), intermedine (4) and four new alkaloids, 7-acetyllycopsamine (5), 7-acetylintermedine (6), symlandine (7)(7-angelyl-9-viridiflorylretronecine) and uplandicine (8) (7-acetyl- 9-echimidinylretronecine).

Measurement of Ankle Joint Swelling Using a Figure of 8

The method of measuring joint swelling in a figure of 8 has the following advantages: 1) being readily reproducible, 2) measuring swelling at the various sites of ankle sprains, and 3) requires only a tape measure and marking pen.J Orthop Sports Phys Ther 1979;1(1):51-52.

Comfrey. fodder, food and remedy

Comfrey. fodder, food and remedy

Carcinogenic Activity of &lt;italic&gt;Symphytum officinale&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;

The carcinogenicity of Symphytum officinale L., Russian comfrey, used as a green vegetable or tonic, was studied in inbred ACI rats. Three groups of 19--28 rats each were fed comfrey leaves for 480--600 days; four additional groups of 15--24 rats were fed comfrey roots for varying lengths of time. A control group was given a normal diet. Hepatocellular adenomas were induced in all experimental groups that received the diets containing comfrey roots and leaves. Hemangioendothelial sarcoma of the liver was infrequently induced.

Alkaloids and other compounds of Symphytum tuberosum

Alkaloids and other compounds of Symphytum tuberosum

On the nitrogen content of Russian comfrey

Russian comfrey の新鮮葉100g 風乾葉10g に水， 10%食塩水， 70% アルコーノレ液， 3.3%苛性ソーダ溶液， 0.3% 苛性ソーダ60% アノレコーノレ液を順次10 倍量宛加え，同じ操作を3回繰返しその合一＊液について窒素を測定した.各種溶剤可溶の窒素総量は全室奈量に対し新鮮葉は60%，風乾葉は47%で稿少ない.また試料の風乾lとより各種溶剤可溶窒素は総量lこ対し， 10%食境水可溶窒素量はその割合を減少するが， 0.3% 苛性ソーダ可溶窒素量はその割合を増加lする.純蛋白質においても同様の傾向がみられる. これは乾燥のため蛋白質に変性をきたしたもので試料保取の時期を異にしても同様な結果を示す.なおアンモニア態，硝酸態，アミノ態，アミド態，ペプチド態窒素をも測定し，特に硝酸と家畜Methemoglobinemia との関係を検討した.