Feverfew Extract Research Articles

Topical formulations containing parthenolide-free extract of feverfew are highly effective in clinically reducing erythema induced by irritation or barrier disruption of the skin

Topical formulations containing parthenolide-free extract of feverfew are highly effective in clinically reducing erythema induced by irritation or barrier disruption of the skin

Daily use of a topical formulation containing parthenolide-free extract of feverfew clinically reduces the appearance of erythema due to ultraviolet exposure

Daily use of a topical formulation containing parthenolide-free extract of feverfew clinically reduces the appearance of erythema due to ultraviolet exposure

Parthenolide-free feverfew extract protects the skin against ultraviolet damage and inflammation

Parthenolide-free feverfew extract protects the skin against ultraviolet damage and inflammation

Feverfew for preventing migraine.

Feverfew (Tanacetum parthenium L.) extract is a herbal remedy used for preventing attacks of migraine. To systematically review the evidence from double-blind randomised controlled trials (RCTs) assessing the clinical efficacy and safety of feverfew versus placebo for preventing migraine. Publications describing (or which might describe) double-blind RCTs of feverfew extract for migraine were sought through the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003); PREMEDLINE/MEDLINE (1966 to July 2003); EMBASE (1974 to July 2003); the trials register of the Cochrane Pain, Palliative and Supportive care group (July 2003); and AMED (1985 to July 2003). Manufacturers of feverfew were contacted and the bibliographies of identified articles checked for further trials. Randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew for preventing migraine were included. Trials using clinical outcome measures were included. Trials focusing exclusively on physiological parameters were excluded. There were no restrictions regarding the language of publication. Data on patients, interventions, methods, outcome measures, results and adverse events were extracted systematically. Methodological quality was evaluated using the scoring system developed by Jadad and colleagues. Two reviewers independently selected studies, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. Five trials (343 patients) met the inclusion criteria. Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine. Only mild and transient adverse events were reported in the included trials. There is insufficient evidence from randomised, double-blind trials to suggest an effect of feverfew over and above placebo for preventing migraine. It appears from the data reviewed that feverfew presents no major safety problems.

Contact allergy to Compositae plants in patients with atopic dermatitis

To investigate the frequency of Compositae sensitivity is one of the most important goals of current dermatology and allergology. We have patch tested 30 adult patients suffering from "extrinsic" atopic dermatitis with sesquiterpene lactone mix and Compositae mix including Compositae mix individual ingredients, extracts of arnica (Arnica montana), chamomile (Chamomilla recutita), tansy (Tanacetum vulgare), fever few (Tanacetum parthenium) and yarrow (Achillea millefolium) as well as with specific series for patients with atopic dermatitis. All allergens were purchased from Hermal-Trolab (Reinbek, Germany). There were 6 (20%) patients positive to Compositae mix only, and 3 (10%) patients positive to both Compositae mix and sesquiterpene lactone mix. Among 9 Compositae mix-sensitive patients 8 (88.8%) were positive to at least 1 of its individual ingredients: 5 (55.5%) to chamomile, 4 (44.4%) to arnica, 2 (22.2%) to tansy, and 2 (22.2%) to fever few. Among Compositae-sensitive patients 78.8% had other contact allergies, most often to nickel (33.3%). Since our study represents the first report on contact allergy to Compositae among patients with "extrinsic" type of atopic dermatitis, it substantiates the statement that atopy represents a risk factor for Compositae allergy. In conclusion, the overall prevalence of 30% Compositae-sensitive among patients with "extrinsic" atopic dermatitis detected in our study represents a basal sesquiterpene lactone mix detection rate of 10%, reinforced and safely supplemented by 20% by testing with the Compositae mix.

Feverfew Extracts and the Sesquiterpene Lactone Parthenolide Inhibit Intercellular Adhesion Molecule-1 Expression in Human Synovial Fibroblasts

Previous studies have shown that extracts of the aromatic herb feverfew (Tanacetum parthenium) and one of its bioactive components, parthenolide, have anti-inflammatory properties in vivo and in vitro. We examined both crude feverfew extracts and purified parthenolide for their ability to modulate adhesion molecule expression in human synovial fibroblasts. Pretreatment of synovial fibroblasts with either feverfew extracts or purified parthenolide could inhibit the expression of intercellular adhesion molecule-1 (ICAM-1) induced by the cytokines IL-1 (up to 95% suppression), TNF-α (up to 93% suppression), and, less strongly, interferon-γ (up to 39% suppression). Inhibition of ICAM-1 was dose and time dependent; as little as a 30-min pretreatment with feverfew resulted in inhibition of ICAM-1. The decrease in ICAM-1 expression was accompanied by a decrease in T-cell adhesion to the treated fibroblasts. Other herbal extracts with reported anti-inflammatory effects were similarly tested and did not decrease ICAM-1 expression. The modulation of adhesion molecule expression may be an additional mechanism by which feverfew mediates anti-inflammatory effects.

Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats

Oral administration of the feverfew ( Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.

Patch testing for Compositae allergy.

The main allergenic constituents of Compositae plants are the sesquiterpene lactones (SLs). In recent years, a mixture of three SLs, each with a different sesquiterpene skeleton (alantolactone, dehydrocostuslactone or costunolide), has been routinely used to detect Compositae allergy. The purpose of our study was to establish the value of testing with a range of Compositae extracts. Ninety-seven consecutive patients with exposure pattern dermatitis or hand eczema and gardening as a hobby or occupation were patch tested to the European standard series including SL mix 0.1% pet., Compositae extracts and other relevant allergens. Twenty-six of the 97 patients tested showed allergic reactions to SL mix or Compositae extracts. Fifteen of these showed positive reactions to both the SL mix and Compositae extracts. Eleven patients showed a negative reaction to the SL mix but positive reaction to the Compositae extracts. Dandelion elicited a positive reaction in eight of the 11 SL mix-negative patients and three patients reacted to feverfew. The SL mix failed to detect 38% of our Compositae-sensitive patients. Dandelion extract alone detected 73% of SL-negative patients. Additional testing with feverfew extract would have detected 91% of the SL mix-negative individuals. Our study highlights the importance of testing the response of SL-negative patients to additional Compositae extracts when there is a clinical suspicion of Compositae allergy.

Occupational dermatitis in Danish gardeners and greenhouse workers (III). Compositae-related symptoms.

The clinical part of the study aimed at describing epidemiological and diagnostic aspects of occupational Compositae dermatitis. Patch testing with the sesquiterpene lactone (SL) and Compositae mixes, feverfew extract and supplementary allergens in 250 selected gardeners showed Compositae allergy in 25, 17 females and 8 males. 24 were possibly occupationally sensitized. The mean age was lower and the preponderance of women higher compared to classical Compositae dermatitis, and the distribution and course of the dermatitis most often did not differ from other occupational plant dermatoses. The Compositae mix detected 2x as many as the SL mix, and the overall detection rate with both was 76%, making aimed patch testing necessary. Chrysanthemum (Dendranthema), marguerite daisy (Argyranthemum frutescens) and lettuce (Lactuca sativa) were frequent sensitizers. Occupational type I allergy to Compositae comprised sensitization to Gerbera, chrysanthemum, lettuce, Senecio cruentus and Aster. Among 1657 respondents in the questionnaire part of the study, 824 had worked with Compositae, and 160 (19%) reported occupational Compositae-related symptoms of skin and mucous membranes. Possible risk factors for the development of these were assessed in a stepwise logistic regression model and a history of childhood eczema, hay fever and duration of exposure were significantly associated with Compositae-related irritant and allergic symptoms in both sexes.

Herbal medicines in migraine prevention

The efficacy of feverfew capsules on migraine prophylaxis was investigated in a randomized double-blind, placebo-controlled crossover study in which 50 patients, who had not used feverfew before, participated. The capsules were filled with a dried alcoholic extract of feverfew on microcristalline cellulose and contained 0.5 mg parthenolide. The patients used one capsule (feverfew or placebo) a day. Fourty four patients completed the 9 month study. Both treatment groups suffered the same number of migraine attacks. A prophylactic effect could not be demonstrated for our feverfew preparation, but the patients seemed to have a tendency to use fever symptomatic drugs during the period they used feverfew. This result was not in accordance with the results from two other studies. The difference may be explained by the fact that both other studies included patients who previously reported positive experiences with feverfew preparations for migraine prophylaxis.

A 6-year experience with compositae mix

A Compositae plant mixture consisting of short ether extracts of arnica, German chamomile, feverfew, tansy, and yarrow has been included in the standard series for several years (1985 to 1990) to study the frequency of allergic reactions to Compositae (Asteraceae) species. One hundred eighteen of 3,851 tested individuals gave a positive response (3.1%). Further tests with the single species of the mixture and some additionally tested extracts of chrysanthemums and laurel oil (bay leaf; Lauraceae) revealed a high percentage of reactions to feverfew (70.1%) and lower responses to chrysanthemums (63.6%), tansy (60.8%), chamomile (56.5%), arnica (51.8%), yarrow (51.8%), and the cross-reacting laurel oil (50.5%). Ten of 85 reacted to arnica alone. The results show that it is important to test Compositae extracts in patients with allergic contact dermatitis because these contain (in contrast to a mixture of pure sesquiterpene lactones) other constituents (eg, polyacetylenes, thiophenes) that may also contribute to the acquired hypersensitivity. Unrevealed sources of hand and face eczema (including airborne contact dermatitis) might be diagnosed more frequently.

Sesquiterpene lactones from feverfew, Tanacetum parthenium: isolation, structural revision, activity against human blood platelet function and implications for migraine therapy

The structures of two series of sesquiterpene lactones (the ‘α’-series 11, 12 and 16 and the ‘β’-series 15, 17 and 18) present in the herb feverfew have been revised in the light of both X-ray analysis and chemical correlations. A biosynthetic pathway is proposed, involving a Diels–Alder type addition of oxygen followed by two contrasting rearrangements, starting from a common intermediate, the cyclopentadiene 19, which has not been identified in feverfew extracts but which is related to a recently isolated structure. The activity of some of these metabolites as well as of the major sesquiterpene lactone present in feverfew, parthenolide 2, and some simple synthetic models as inhibitors of human blood platelet function has been determined. The possible relevance of this effect to migraine prophylaxis by feverfew is briefly discussed.

Toxic inhibition of smooth muscle contractility by plant-derived sesquiterpenes caused by their chemically reactive alpha-methylenebutyrolactone functions.

1. Previous studies have shown that extracts of feverfew (Tanacetum parthenium) and parthenolide, a sesquiterpene alpha-methylenebutyrolactone obtained from it, inhibit smooth muscle contractility in a time-dependent, non-specific and irreversible manner. 2. The hypothesis that this toxic effect is due specifically to the presence in the sesquiterpene lactone of the potentially reactive alpha-methylene function was tested on rabbit isolated aortic ring preparations. This was done (a) by comparing the effects of two plant-derived sesquiterpene lactones purified from yellow star thistle (Centaurea solstitialis): cynaropicrin (an alpha-methylenebutyrolactone) and solstitialin 13-acetate (lacking the alpha-methylene function), and (b) by chemically inactivating the alpha-methylene functions in cynaropicrin and parthenolide by reaction with cysteine. 3. The results show that the characteristic smooth muscle inhibitory profile is demonstrated by the two alpha-methylenebutyrolactones (parthenolide and cynaropicrin), but not by the compound lacking this functional group (solstitialin 13-acetate), or by those previously active compounds in which it has been inactivated with cysteine. 4. Thus the alpha-methylene function is critical for this aspect of the toxic pharmacological profile of the sesquiterpene butyrolactones, which are natural products widely distributed in the Compositae family of flowering plants.

A chloroform extract of the herb feverfew blocks voltage-dependent potassium currents recorded from single smooth muscle cells.

We have studied the effects of a chloroform extract of fresh leaves from the herb feverfew (Tanacetum parthenium) on potassium currents in smooth muscle. The currents were recorded from single cells dissociated from the rat anococcygeus and the rabbit ear artery using the whole-cell patch-clamp technique. When applied to cells isolated from the rat anococcygeus, the extract reduced the inactivating voltage-dependent potassium current in a concentration-related manner, with an IC50 value (the concentration that reduced the current by 50%) of 56 micrograms mL-1. Complete block of the current occurred at 1 mg mL-1. In addition to reducing the peak current, feverfew decreased the time to peak of the current and increased the rate of decay of the current. These effects can be explained by the feverfew extract blocking open potassium channels. In single cells isolated from rabbit ear artery the feverfew extract again reduced the voltage-dependent potassium current, whilst at the same time having no effect on the spontaneous transient outward currents which arise as a consequence of activation of calcium-dependent potassium channels. These results suggest that chloroform extracts of feverfew leaf contain an as yet unidentified substance capable of producing a selective, open-channel block of voltage-dependent potassium channels.

Feverfew extracts and parthenolide irreversibly inhibit vascular responses of the rabbit aorta.

Samples prepared from chloroform extracts of fresh leaves of feverfew (Tanacetum parthenium) strongly inhibited responses of rabbit aortic rings to phenylephrine, 5-hydroxytryptamine, thromboxane mimetic U46619 (9,11-dideoxy-11 alpha,9 alpha-epoxy-methano-PGF2 alpha), and angiotensin II, but the inhibition to contractions induced by potassium depolarization was much less. The inhibition was concentration- and time-dependent, non-competitive, and irreversible, and also occurred in endothelium-denuded preparations. The feverfew extracts also caused a progressive loss of tone of pre-contracted aortic rings and appeared to impair the ability of acetylcholine to induce endothelium-dependent relaxations of the tissue. These effects were mimicked by a purified preparation of an alpha-methylenebutyrolactone, parthenolide, obtained from the extract. Our results demonstrate a nonspecific and potentially toxic response to feverfew on the vasculature.

Inhibition of 5-lipoxygenase and cyclo-oxygenase in leukocytes by feverfew: Involvement of sesquiterpene lactones and other components

Leaves or infusions of feverfew, Tanacetum parthenium, have long been used as a folk remedy for fever, arthritis and migraine, and derived products are widely available in U.K. health food shops. Previous reports have suggested interactions with arachidonate metabolism. Crude chloroform extracts of fresh feverfew leaves (rich in sesquiterpene lactones) and of commercially available powdered leaves (lactone-free) produced dose-dependent inhibition of the generation of thromboxane B 2 (TXB 2) and leukotriene B 4 (LTB 4) by ionophore- and chemoattractant-stimulated rat peritoneal leukocytes and human polymorphonuclear leukocytes. Approximate 1050 values were in the range 5–50 μg/mL, and inhibition of TBX 2 and LTB 4 occurred in parallel. Isolated lactones (parthenolide, epoxyartemorin) were also inhibitory, with approximate ic 50 values in the range 1–5 μg/mL, as were crude extracts treated with cysteine (to neutralize reactive α-methylene butyrolactone functions of the sesquiterpenes). Inhibition of eicosanoid generation appeared to be irreversible but not time-dependent. We conclude that feverfew contains a complex mixture of sesquiterpene lactone and non-sesquiterpene lactone inhibitors of eicosanoid synthesis of high potency, and that these biochemical actions may be relevant to the claimed therapeutic actions of the herb.

Parthenolide content and bioactivity of feverfew (Tanacetum parthenium (L.) Schultz-Bip.). Estimation of commercial and authenticated feverfew products.

Three physicochemical methods (HPLC, NMR spectroscopy, and HPLC of a derivative) have been used to measure parthenolide in authenticated Tanacetum parthenium (feverfew) and in several commercial purported feverfew products. A bioassay based on inhibition of the secretory activity of blood platelets by extracts of feverfew in comparison with parthenolide was also used. Similar results were obtained for all three physicochemical assays and also for the bioassay. Thus different methodologies yield consistent values for parthenolide content of feverfew preparations. Parthenolide appears to be mainly responsible for the antisecretory effects of extracts of feverfew. Authenticated Tanacetum parthenium grown in the UK contained a high level of parthenolide in leaves, flowering tops and seeds but a low level in stalks and roots. The level of parthenolide in powdered leaf material fell during storage. The purported feverfew products varied widely in their parthenolide content and in some products parthenolide was not detected. Possible reasons for the variation in parthenolide content are discussed. Since therapeutic efficacy has only been demonstrated for preparations of feverfew that contain parthenolide, it is suggested that manufacturers of feverfew products should use measurements of parthenolide as a means of standardization and quality control.

A Comparison of the Effects of an Extract of Feverfew and Parthenolide, a Component of Feverfew, on Human Platelet Activity In-vitro

Extracts of the herb feverfew inhibit human blood platelet aggregation and secretion induced by a number of agents in-vitro and this may relate to the beneficial effects of feverfew in migraine. We previously identified several compounds with antisecretory activity in human blood platelets using adrenaline as the stimulant. In the present study, we have compared the inhibitory activity of one of these compounds, parthenolide, with that of crude feverfew extract. The effects of both on [14C]5-HT secretion from platelets and on platelet aggregation induced by a number of different stimulants were determined. The activating agents studied included the phorbol ester PMA, ADP, arachidonic acid, collagen, the thromboxane mimetic U46619, the calcium ionophore A23187, the diacylglycerol analogue OAG and adrenaline. The results show that there are marked similarities between the effects of feverfew extract and of parthenolide on both [14C]5-HT secretion and platelet aggregation, which is consistent with the effects of feverfew extract on platelets being brought about by parthenolide or similar compounds in the extract. Only in one case, when A23187 was used as the stimulatory agent, was there any discrepancy, which may have been due to materials in the extract other than parthenolide. Both feverfew extract and parthenolide were more effective as inhibitors of the [14C]5-HT secretion and aggregation induced by some agents and not others, and were most effective as inhibitors of the [14C]5-HT secretion (but not the aggregation) induced by PMA. This suggests that the effects of feverfew/parthenolide on the protein kinase C pathway warrants further study.

Effects of an extract of feverfew on endothelial cell integrity and on cAMP in rabbit perfused aorta.

Extracts of feverfew inhibit platelet aggregation and secretion of granular contents from platelets and other cells. They also modify the interaction of platelets with collagen substrates: feverfew extracts inhibit both platelet spreading and formation of thrombus-like platelet aggregates on the collagen surface. We have now investigated the effect of an extract of feverfew on the vessel wall using rabbit aortas that were perfused with a physiological salt solution in-situ. Addition of feverfew extract to the perfusion medium protected the endothelial cell monolayer from perfusion-induced injury and led to a reversible increase in the cAMP content of aorta segments. The results indicate that feverfew may have a vasoprotective effect in addition to its effects on platelets.

Extracts of feverfew inhibit mitogen-induced human peripheral blood mononuclear cell proliferation and cytokine mediated responses: A cytotoxic effect

The term ‘favism’ is used to indicate a severe reaction occurring on ingestion of foodstuffs consisting of or containing the beans of the leguminous plant Vicia faba (fava bean, broad bean). Within 6–24 h of the fava bean meal, the reaction manifests itself with prostration, pallor, jaundice, and dark urine. These signs and symptoms result from (sometimes massive) destruction of red blood cells (RBCs; acute hemolytic anemia), triggered by certain glucosides (divicine and convicine) present at high concentrations in the fava beans. These glucosides cause severe damage to RBCs only if the cells are deficient in the enzyme glucose-6-phosphate dehydrogenase (or G6PD); therefore, favism occurs only in people who have inherited G6PD deficiency. Favism is more common and more life-threatening in children (usually boys) than in adults; however, once the attack is over, a full recovery is usually made. In a person who is G6PD deficient, favism can recur whenever fava beans are eaten, although whether this happens or not is greatly influenced by the amount of beans ingested and probably by many other factors. From the public health point of view, it has been proven that favism can be largely prevented by screening for G6PD deficiency and by education through the mass media.