Feverfew, a member of the Asteraceae or Compositae family, is a perennial herb with a long history of traditional use.
The expression "feverfew" is derived from the Latin for fever reducer. Evidence of the anti-inflammatory properties of feverfew has been accruing over the last several decades and is now considered well established (Carcinogenesis 2004;25:1449-58).
Photo (c)Courtesy Wikimedia Commons/Dr Paul G Tuli/Creative Commons License
The feverfew extract parthenolide has anti-tumor and anti-inflammatory properties, but it has also been found to cause contact dermatitis and allergic reactions in some individuals.
In a Medline literature review of herbal agents that many people take but that might warrant discontinuing before dermatologic surgery, authors cited feverfew for its known success as a treatment for migraines (Br. Med. J. [Clin. Res. Ed.] 1985;291:569-73). In addition, feverfew is known for success in treatment for arthritis, as well as its anti-inflammatory activity in blocking phospholipase breakdown of arachidonic acid into prostaglandins and leukotrienes (Dermatol. Surg. 2001;27:759-63; Prostaglandins Leukot. Med. 1982;8:653-60).
They noted that platelet aggregation is also induced by the feverfew extract parthenolide and a byproduct of the arachidonic acid cascade, thromboxane A (Dermatol. Surg. 2001;27:759-63; J. Pharm. Pharmacol. 1990;42:553-7; J. Pharm. Pharmacol. 1987;39:459-65). Parthenolide is obtained as a hydroalcoholic extract of aerial parts of the plant, and is known to inhibit nuclear factor–kappaB (NF-kappaB) and to exhibit antiproliferative properties (Biochem. Biophys. Res. Commun. 2005;332:321-5). Feverfew also contains the potent antioxidant melatonin (Lancet 1997;350:1598-9).
Parthenolide Potency
Parthenolide has been consistently shown to exhibit in vitro antitumor activity (Mol. Cancer Ther. 2005;4:1004-12). A recent in vitro and in vivo investigation of the cancer chemopreventive potential of parthenolide using the UVB-induced skin cancer model revealed that SKH-1 hairless mice that were given parthenolide exhibited later onset of papillomas and significantly fewer papillomas in comparison to mice that were exposed only to UVB but not fed the primary component of feverfew. The in vitro phase of the study, which used cultured JB6 murine epidermal cells, showed that noncytotoxic concentrations of parthenolide pretreatment significantly suppressed UVB-induced activator protein-1 DNA binding and transcriptional activity, as well as JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase signaling activation, all of which might be crucial in the anticancer mechanism of action of parthenolide, according to the authors (Carcinogenesis 2004;25:1449-58). In a study conducted by three of the same investigators, parthenolide was found to sensitize UVB-induced apoptosis through pathways that depend on protein kinase C (Carcinogenesis 2005;26:2149-56).
In another recent study, investigators found that parthenolide effectively blocked the gene expression mediated by NF-kappaB and the production of bFGF (basic fibroblast growth factor) and MMP-1 (matrix metalloprotease-1) as well as the UVB-induced proliferation of keratinocytes and melanocytes in mouse skin, prompting the conclusion that inhibitors of NF-kappaB, particularly parthenolide, have potential to prevent cutaneous photoaging (J. Pharmacol. Exp. Ther. 2005;315:624-30).
In addition to its potential activity against skin cancer and photoaging, the feverfew constituent parthenolide confers other benefits pertinent to dermatology. Researchers recently identified potent intracellular antioxidant activity displayed by parthenolide in hippocampal HT22 cells, properties that are mediated by an increase of glutathione but not found to mediate the sesquiterpene lactone’s antiproliferative activities or its suppression of NF-kappaB (Biochem. Biophys. Res. Commun. 2005;332:321-5).
Parthenolide has also shown marked leishmanicidal activities suitable enough, according to investigators, to be considered for inclusion in the development of new drugs to treat this disease (Antimicrob. Agents Chemother. 2005;49:176-82).
Although several in vitro studies have indicated that parthenolide imparts anti-inflammatory effects, a recent in vivo study with mice demonstrated that the sesquiterpene lactone component of feverfew modestly suppressed only one gene, interleukin-6 after lipopolysaccharide-induced increases (J. Inflamm. (Lond). 2005;2:6). The authors concluded that more study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using animal models is needed to assess the efficacy of various supplements.
A recent finding regarding parthenolide indicates the expanding breadth and depth of the potential medical applications of this herbal extract. Parthenolide was recently found to exhibit significant activity in suppressing hepatitis C virus, which is often a precursor to cirrhosis and hepatocellular carcinoma (J. Inflamm. [Lond]. 2005;2:6). In hepatoma cells, parthenolide has been found to enhance the apoptosis induced by fenretinide (N-4-hydroxyphenyl retinamide, or 4-HPR), a synthetic anticancer retinoid and an established apoptosis-inducing agent. In a study focusing on the relationship of these two compounds, parthenolide was found to upregulate or downregulate 35 apoptosis-related genes, and its role as an adjuvant anticancer agent against hepatoma was elucidated (Cancer Res. 2005;65:2804-14).
Parthenolide has demonstrated potential activity against several other cancer types. The herbal compound has been found to preferentially induce apoptosis in acute myelogenous leukemia stem cells without adversely affecting normal blood cells (Expert Opin. Biol. Ther. 2005;5:1147-52). In a recent study, parthenolide dose-dependently induced apoptosis in all four cholangiocarcinoma cell lines with sarcomatous SCK cells more sensitive to parthenolide than the other adenomatous cholangiocarcinoma cells. Investigation of the greater susceptibility of SCK cells to parthenolide revealed Bcl-2 family molecular involvement, and indicated that impaired expression of Bcl-X(L) might play a role in the greater sensitivity of SCK cells, compared with other adenomatous cholangiocarcinoma cells, to parthenolide (Cancer Res. 2005;65:6312-20).