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Common Comfrey (Symphytum officinale) and Inflammation (general): evidence and sources
inferred from anti-inflammatory action
For educational purposes only, not medical advice. Always consult a qualified practitioner before using medicinal plants, especially alongside prescribed medication, during pregnancy, or for a serious condition.
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Comfrey has a centuries-old tradition as a medicinal plant. Today, multiple randomized controlled trials have demonstrated the efficacy and safety of comfrey preparations for the topical treatment of pain, inflammation and swelling of muscles and joints in degenerative arthritis, acute myalgia in the back, sprains, contusions and strains after sports injuries and accidents, also in children aged 3 or 4 and over. This paper provides information on clinical trials and non-interventional studies published on comfrey to date and further literature, substantiating the fact that topical comfrey preparations are a valuable therapy option for the treatment of painful muscle and joint complaints.
Ethnopharmacological relevance Symphytum officinale L. (comfrey, Boraginaceae) has been traditionally used for millennia in joint distortions, myalgia, bone fractures and hematomas. However, key activity-determining constituents and molecular mechanisms underlying its use have not been completely elucidated. Aim of the study The objective of this study was to isolate and identify the major compounds from a hydroethanolic root extract of S. officinale and evaluate their antioxidant potential, alongside their effect on the cytokine production of ex vivo stimulated neutrophils, thus providing scientific support for the traditional use of comfrey root. Material and methods Four caffeic acid oligomers were isolated from comfrey roots by liquid-liquid chromatography, their structures being established by MS and NMR analyses. In vitro antioxidant evaluation was performed by DPPH and ABTS assays. The cytotoxicity of isolated compounds was established by flow cytometry. The effect on cytokine release, such as interleukin (IL)-1β, IL-8 and tumor necrosis factor alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated neutrophils was determined by enzyme-linked immunosorbent assay (ELISA). Results The main constituents found in comfrey root were represented by four caffeic acid oligomers, namely globoidnan B (1), rabdosiin (2), rosmarinic acid (3) and globoidnan A (4). Rabdosiin, globoidnans A and B were isolated for the first time from S. officinale. In the in vitro antioxidant tests, compound 2 was the most active, with EC 50 values in DPPH and ABTS assays of 29.14 ± 0.43 and 11.13 ± 0.39, respectively. Neutrophils' viability over the tested concentration domain of 12.5-50 μM was not altered. At 50 μM, all compounds significantly inhibited IL-1β release, with compound 3 (45.60% release vs. LPS stimulated neutrophils) being the most active, followed by compounds 1 (53.85%), 2 (69.89%) and 4 (60.68%). Conclusions The four caffeic acid oligomers reported in S. officinale root may contribute to the overall anti-inflammatory activity for which comfrey preparations are used in traditional medicine.
4 sources supporting Common Comfrey for Inflammation (general). Includes scientific publications, books, monographs and traditional-use references.
Mechanistic basis
This use is associated with the plant's anti-inflammatory action. Further evidence for that pharmacology:
Comfrey ( Symphytum officinale L.) contains rosmarinic acid which has different pharmacological activities, such as antioxidant and anti-inflammatory activities. However, the medicinal use of comfrey is limited by the hepatotoxic effect of lycopsamine in comfrey, which overshadows the health benefits of rosmarinic acid. Natural deep eutectic solvents (NADES) have a wide range of extraction properties, that provides a new approach to the detoxification of comfrey. In the present study, betaine-based and choline chloride-based NADES were screened for selective extraction of rosmarinic acid over lycopsamine. Ultrasonication was used in conjunction with NADES extraction. The chemical profile of the NADES extracts on antioxidant, anti-inflammatory and hepatotoxic activities were investigated using some chemical reagents. Betaine-urea (1:2 molar ratio, 50% water) obtained the highest content of rosmarinic acid and a low level of lycopsamine (1.934 and 0.018 mg/g, respectively). Betaine-urea was also shown to be more effective to extract rosmarinic acid compared to methanol-UAE under the same conditions, which gave lower rosmarinic acid and higher lycopsamine levels (0.007 and 0.031 mg/g, respectively). Betaine-urea extracts showed higher antioxidant and anti-inflammatory properties as compared with other NADES extracts, however, had lower hepatotoxic profile. This study recommends the use of betaine-urea to detroxify comfrey to open wider opportunities for the development of comfrey for medicinal use.
Background External preparations of the herb comfrey (most commonly Symphytum officinale L.) are widely available for over-the-counter, practitioner and healthcare professional usage. Traditional practice suggests comfrey can be used to treat musculoskeletal disorders, wounds and various other conditions; however a full and critical coverage of the evidence base has not yet been undertaken. Methods A critical scoping review was undertaken. Six bibliographic databases, 10 grey literature databases and nine trials registers were searched plus reference lists of included studies and a descriptive overview of comfrey. Randomised or non-randomised clinical trials assessing the external use of comfrey for any indication were included and methodological and reporting quality were assessed. Observational studies were included only in the assessment of adverse events. Studies were grouped and summarised according to the type of indication treated. Results Of 1348 identified records, 64 full texts were screened for inclusion and 26 were included in the review - 13 RCTs, 5 non-randomised controlled trials and 8 observational studies evaluating treatments for ankle distortion, back pain, abrasion wounds, venous leg ulcers and osteoarthritis. The majority of included trials had an overall unclear risk of bias due to poor quality of reporting. Few adverse events were reported. Conclusions Individual clinical trials showed evidence of benefit for ankle distortion, back pain, abrasion wounds and osteoarthritis. Topical application appears to be safe but further rigorous assessment is needed. Systematic reviews focussing on particular indications may clarify the treatment effect and safety of external comfrey preparations.
Comfrey root preparations are used for the external treatment of joint distortions and myalgia, due to its analgesic and anti-inflammatory properties. Up to date, key activity-determining constituents of comfrey root extracts have not been completely elucidated. Therefore, we applied different approaches to further characterize a comfrey root extract (65% ethanol). The phenolic profile of comfrey root sample was characterized by HPLC-DAD-QTOF-MS/MS. Rosmarinic acid was identified as main phenolic constituent (7.55 mg/g extract). Moreover, trimers and tetramers of caffeic acid (isomers of salvianolic acid A, B and C) were identified and quantified for the first time in comfrey root. In addition, pyrrolizidine alkaloids were evaluated by HPLC-QQQ-MS/MS and acetylintermedine, acetyllycopsamine and their N-oxides were determined as major pyrrolizidine alkaloids in the comfrey root sample. Lastly, the antioxidant activity was determined using four assays: DPPH and ABTS radicals scavenging assays, reducing power assay and 15-lipoxygenase inhibition assay. Comfrey root extract exhibited significant antioxidant activities when compared to known antioxidants. Thus, comfrey root is an important source of phenolic compounds endowed with antioxidant activity which may contribute to the overall bioactivity of Symphytum preparations.