Parthenolide anti-inflammatory effects

Organic and aqueous feverfew powdered leaf extracts were found to inhibit IL-1-induced prostaglandin E2 release from synovial cells, IL-2-induced thymidine uptake by lymphoblasts, and mitogen-induced uptake of thymidine by peripheral blood mononuclear cells (PBMCs) (23). Parthenolide also inhibited thymidine uptake by PBMCs. Both parthenolide and the extracts were cytotoxic to the PBMCs and synovial cells thus, the anti-inflammatory effects of feverfew may be secondary to cytotoxicity. These results reflect those of previous researchers who found parthenolide and other sesquiterpene lactones to be cytotoxic to cultures of human fibroblasts, human laryngeal carcinoma cells, and human cells transformed with simian virus 40 (24). 

Based on previous reports of antiinflammatory activity, a 1989 double-blind, placebo-controlled, randomized study evaluated the effect of dried leaves (70-86 mg) in the treatment of rheumatoid arthritis. Over the 6-week trial, 41 female patients with symptomatic rheumatoid arthritis received feverfew or placebo. More than 13 laboratory and/ or clinical parameters were assessed. The authors concluded that there were no important differences between the control group and those receiving feverfew. Participating patients, however, had not previously responded to conventional therapies. The results do not preclude possible benefits for the use of feverfew in osteoarthritis and soft tissue lesions. Later in vivo studies showed that both feverfew extract and parthenolide possessed antiinflammatory and antinociceptive activities in mice and rats and that such activities were dose dependent. The extract, parthenolide, and some of the constituent flavonoids were also shown to inhibit the arachidonic acid pathways in leukocytes. Another possible mechanism for the anti-inflammatory effect of feverfew is the inhibition of the expression of intercellular adhesion molecule-1 (ICAM-1). ... 

Tanacetum parthenium (Asteraceae), commonly known as feverfew, is a popular herbal remedy used a prophylactic in the treatment of migraine [88]. Studies have revealed that the action of feverfew is probably mediated by the sesquiterpene lactone parthenolide. Indeed, feverfew and parthenolide produce anti-inflammatory and antinociceptive effects in experimental animals [89]. Parthenolide is a potent inhibitor of the transcription factor NF-kB activation, a key regulator of pro-inflammatory protein production, such as cytokines, COX-2 and inducible nitric oxide synthase [90]. However, a clinical study revealed that feverfew did not provide any benefit in the treatment of rheumatoid arthritis [91]. Additional clinical studies must be carried out to explore the feverfew efficacy as an analgesic. 

Parthenolide, isolated from Tanacetum parthenium and other species, is a sesquiterpene lactone widely investigated for its anti-inflammatory activity [168,169,170]. Recent in vitro studies have shown that this compound inhibits the NF-kB pathway. A study on the effect of parthenolide in endotoxic shock in rodents showed that treatment with this compound stopped nitrotyrosine formation, PARP synthetase expression, and apoptosis. It also reduced iNOS mRNA content in the tissues studied. All these effects are brought about by the compound s inhibition of NF-kB [171]. In addition, parthenolide mimicked the effects of IkBoc in that it inhibited both NF-kB DNA binding activity as well as Mn-SOD expression, while simultaneously increasing paclitaxel-induced apoptosis of breast cancer cells [90]. 

Parthenolide (18) Anti-inflammatory and anti-hyperalgesic effects potential cancer drug... 

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