Feverfew (Tanacetum parthenium)
Tanacetum parthenium (feverfew), a member of the Asteraceae family, is a phytomedicine that has become very popular since the 1980s in treating inflammatory conditions and migraine. The ancient Greeks called the herb “Parthenium,” supposedly because it was used medicinally to save the life of someone who had fallen from the Parthenon during its construction in the 5th century BC. The first-century Greek physician Dioscorides used feverfew as an antipyretic. Feverfew also was known as “medieval aspirin” or the “aspirin” of the 18th century.
It is widely used in traditional medicine for the treatment of fevers, migraine headaches, rheumatoid arthritis, stomachache, toothache, insect bites and infertility. Feverfew has also been used for psoriasis, allergies, asthma, tinnitus, dizziness, nausea, and vomiting. Feverfew extracts also possess antiprotozoal, antibacterial, anti-inflammatory, and antioxidant properties.
In Central and South America, the plant has been used to treat a variety of disorders. The Kallaway Indians of the Andes mountains value its use for treating colic, kidney pain, morning sickness, and stomachache. Costa Ricans use a decoction of the herb to aid digestion, as a cardiotonic, an emmenagogue, and as an enema for worms. In Mexico, it is used as an antispasmodic and as a tonic to regulate menstruation. In Venezuela, it is used for treating earaches.
The most important biologically active components are the sesquiterpene lactones, the principal one being parthenolide. Parthenolide is found in the superficial leaf glands (0.2%–0.5%), but not in the stems, and comprises up to 85% of the total sesquiterpene content. Thus, more than 30 sesquiterpene lactones have been identified in feverfew. In general, there are 5 different types of sesquiterpene lactones, which may be classified by chemical ring structures. Feverfew contains eudesmanolides, germacranolides, and guaianolides. Parthenolide is a germacranolide.
Researchers have also isolated the following sesquiterpene lactones: artecanin, artemorin, balchanin, canin, costunolide, 10-epicanin, epoxyartemorin, 1-beta-hydroxyarbusculin, 3-beta-hydroxycostunolide, 8-alpha-hydroxyestagiatin, 8-beta hydroxyreynosinn, 3-beta-hydroxyparthenolide, manolialide, reynosin, santamarine, epoxysantamarine, secotanaparthenolide A, secotanaparthenolide B, tanaparthin-alpha-peroxide, and 3,4-beta-epoxy-8-deoxycumambrin B.
In clinical studies, a feverfew extract reduced the frequency of migraine attacks; a formulation containing feverfew was reported useful in decreasing the duration of aura; and a feverfew/ginger formula prevented mild headache before the onset of moderate to severe headache in patients with migraine. In another study, a combination of feverfew and acupuncture treatments led to greater improvements in quality of life in women with migraine, compared with feverfew or acupuncture alone. But a clinical trial did not find any benefit of feverfew in patients with rheumatoid arthritis.
In addition, parthenolide demonstrated anticancer effects in vitro. A phase I clinical study involving cancer patients showed that up to 4 mg of parthenolide was well tolerated; however, it could not be detected in the plasma. Consequently, a synthetic analog dimethylamino-parthenolide (DMAPT), a more hydrophilic form of parthenolide, with greater bioavailability was identified. Oral administration of DMAPT has been found to be safe and resulted in increased plasma concentrations in an animal model.
The sesquiterpene lactones, particularly parthenolide, are the active constituents responsible for feverfew’s beneficial effects. Parthenolide attenuates activation of the NF-kappa B complex to block transcription of inflammatory proteins. The inhibition of this pathway also leads to decreased platelet activity. Other mechanisms that produce antiplatelet activity by parthenolide include sulfhydryl group alterations, changes in protein kinase C interactions, and arachidonic acid metabolism. The flavonol content also has anti-inflammatory effects.
Although much of its activity is attributed to the compound parthenolide, a parthenolide-free extract of feverfew demonstrated free radical-scavenging properties, affording protection against UV-induced sun damage.
In vitro studies suggest various activities induced by parthenolide can produce antiproliferative effects. In colorectal cancer cells, it suppresses angiogenesis by reducing VEGF and VEGF-receptor expression. In cervical and breast cancer cell lines, parthenolide modulates apoptosis-regulating gene expression and activates both apoptosis pathway and AMPK-autophagy survival pathway through ROS generation. In glioblastoma cells, it induces caspase 3/7-mediated apoptosis independent of NF-kappa B suppression. Parthenolide sensitizes the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) leading to apoptosis via activation of both caspases 8 and 3 in hepatocellular carcinoma cells.
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