Anti-Inflammatory Activity of Parthenolide-Depleted Feverfew (Tanacetum parthenium)

Extracts of Tanacetum parthenium (L.) Sch. Bip., a plant known under the common name “Feverfew”, contains the sesquiterpene lactone parthenolide, a potent skin sensitizer. To eliminate the risk of skin sensitization from Feverfew, we developed a parthenolide-depleted extract of Feverfew (PD-Feverfew) and determined its effectiveness as an anti-inflammatory agent. We confirmed that PD-Feverfew was sufficiently depleted of parthenolide since PD-Feverfew did not inhibit TNF-α induced-NF-κB activity unlike parthenolide containing whole Feverfew. PD-Feverfew directly inhibited the activity of pro-inflammatory enzymes 5-lipoxygenase, phosphodiesterase-3 and phosphodiesterase-4. PD-Feverfew inhibited the release of pro-inflammatory mediators nitric oxide, PGE₂ and TNF-α from macrophages and TNF-α, IL-2, IFN-γ and IL-4 from human peripheral blood mononuclear cells. Additionally, PD-Feverfew inhibited TPA-induced release of PGE₂ from human skin equivalents. In vivo, PD-Feverfew inhibited oxazolone-induced dermatitis, and was more potent than whole Feverfew in reducing TPA-induced dermatitis. Finally the efficacy of PD-Feverfew was confirmed clinically by a reduction in erythema in a methyl nicotinate-induced vasodilation model. In conclusion, our results indicate that PD-Feverfew extracts have potent anti-inflammatory activity suggesting that this botanical would be efficacious in relieving inflammation without inducing immune sensitization.     

小白菊内酯诱导肝癌细胞SMMC 7721自噬性死亡的实验研究

目的 探讨小白菊内酯对肝癌细胞SMMC 7721自噬反应的影响及其机制。方法 通过MTT测定小白菊内酯对 SMMC 7721细胞活力的影响;通过吖啶橙染色观察不同浓度小白菊内酯对SMMC 7721细胞自噬的影响,Western blot检测细胞自噬标志物LC3、p62的表达以及自噬流检测分析小白菊内酯对细胞自噬的影响;用抗氧化剂NAC去除细胞中ROS,通过Western blot检测小白菊内酯对细胞自噬的影响,确定ROS在其中的作用。结果 小白菊内酯可抑制SMMC 7721细胞的增殖,并具有浓度依赖性;通过自噬的标志物及自噬流的检测显示小白菊内酯可诱导肝癌细胞系SMMC 7721细胞发生自噬,用NAC去除ROS后,小白菊内酯引起的自噬明显下降,说明其诱导的SMMC 7721细胞发生自噬依赖于ROS。 结论 小白菊内酯可能是通过刺激细胞产生ROS诱导SMMC 7721肝癌细胞发生自噬性死亡。     

Feverfew: weeding out the root of leukaemia

Malignant stem cells are central to the pathogenesis and perpetuation of acute myelogenous leukaemia (AML). Despite their crucial role, standard chemotherapy often does not target these critical cells and, thus, the ‘root’ of leukaemic disease is not eradicated. To derive better therapies, unique molecular features of malignant stem cells have been characterised for AML and evaluated with regard to ablation of disease. In the course of such studies, the compound parthenolide, which is derived from the medicinal plant feverfew, has recently been shown to preferentially induce AML stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect on normal blood cells. Thus, this naturally occurring agent may provide new avenues of investigation for the treatment of leukaemia. In this article, characteristics of parthenolide are reviewed.     

Parthenolide-depleted Feverfew (Tanacetum parthenium) protects skin from UV irradiation and external aggression

The skin is under continual assault from a variety of damaging environmental factors such as ultraviolet irradiation and atmospheric pollutants, and as organisms age the cumulative damage exceeds the capacity of endogenous antioxidant defenses resulting in chronic inflammation and premature aging. Botanical extracts such as Feverfew containing naturally occurring antioxidants could replenish the depleted cutaneous stores and perhaps forestall these degenerative changes. A parthenolide-depleted extract of Feverfew (PD-Feverfew), which was free of sensitization potential, was found to possess free radical scavenging activity against a wide range of reactive oxygen species and with greater activity than Vitamin C. In vitro, PD-Feverfew restored cigarette smoke-mediated depletion of cellular thiols, attenuated the formation of UV-induced hydrogen peroxide and reduced pro-inflammatory cytokine release. In vivo, topical PD-Feverfew reduced UV-induced epidermal hyperplasia, DNA damage and apoptosis. In a clinical study PD-Feverfew treatment significantly reduced erythema versus placebo 24 h post-UV exposure. Through the ability to scavenge free radicals, preserve endogenous antioxidant levels, reduce DNA damage and induce DNA repair enzymes, which can help repair damaged DNA, parthenolide-depleted extract of Feverfew may protect skin from the numerous external aggressions encountered daily by the skin and reduce the damage to oxidatively challenged skin.     

The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis--a double-blind,multicentre, randomized placebo-controlled dose-response study

Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.     

5-Hydroxytryptamine-inhibiting property of Feverfew: role of parthenolide content

AIM: To study the mechanism of antimigraine activity of Tanacetum parthenium ( Feverfew), its extracts and parthenolide, a component of Feverfew, by observing their effect on 5-HT storage and release, and stimulation of 5-HT2B and 5-HT2A receptors. Also to standardize a dosage form of Feverfew with respect to its parthenolide content. METHODS: Isometric responses to 5-HT and an indirect acting serotonergic, d-fenfluramine, were obtained on rat fundus and ileum. In one set of experiments the effect of dichloromethane extract of Feverfew and parthenolide was observed on the above. The extract was then thermally degraded upto 10 %, 23 %, and 33 % with respect to its parthenolide content by keeping at 60℃ and 75 % relative humidity and the experiments were repeated. In another set of experiments rats were fed with 20 mg/kg Feverfew powder (equivalent to a human dose of 500 μg parthenolide per day) for 30 d or were ip injected with parthenolide (23.4 μg/day) for 7 d. In the same set of experiments one gro     

A reproductive screening test of feverfew: is a full reproductive study warranted?

Feverfew is currently used in the treatment of migraine and arthritis. It is traditionally contraindicated in pregnancy but there are no studies confirming this warning. An in vivo and in vitro preliminary screen was performed using a rat model: five female rats were orally dosed with 839 mg/kg feverfew daily on either gestation days (GD) 1–8 or 8–15. On GD20, rats were sacrificed and fetuses, placentae and ovaries were collected. The fetuses were weighed and examined for malformations. While maternal weight gain appeared to be reduced, ANCOVA analysis suggested that the difference was due to litter size, rather than treatment. Pre-implantation loss appeared increased but this was not statistically significant in the feverfew GD1–8 group. Fetuses exposed to feverfew from GD8–15 were smaller than ethanol controls perhaps as a result of the increased frequency of runts in treated litters. Feverfew induced toxicity when GD10.5 embryos were cultured for 26 h in rat serum to which extract was added. The results of the present preliminary study suggest that a comprehensive reproductive study of feverfew is warranted.