parthenolide

Parthenolide is a sesquiterpene lactone of the germacranolide class, naturally occurring in the plant feverfew (Tanacetum parthenium) and related species. It is considered the main bioactive component of feverfew and has been studied for its anti-inflammatory, anticancer, anti-migraine, and antinociceptive properties[5][6][8]. Parthenolide acts through multiple mechanisms including inhibition of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity (via interaction with IKK or directly with p65), inhibition of Signal transducer and activator of transcription protein family (STAT) and Mitogen activated protein kinase activities, reduction of Histone deacetylase 1 (HDAC1) levels, inhibition of DNA methyltransferase 2 homolog DNMT2/TRDMT1 activity leading to global DNA hypomethylation, induction of ROS accumulation in cancer cells resulting in apoptosis, partial agonism at transient receptor potential ankyrin 1 (TRPA1) channels (desensitizing them), agonism at adiponectin receptor 2 (AdipoR2), inhibition of NLR family pyrin domain containing 3 (NLRP3) ATPase activity and caspase 1 protease activity[5][6][8]. Parthenolide selectively induces cell death in cancer cells while sparing normal cells and may target cancer stem cells. Its poor water solubility and low bioavailability limit its clinical use. It has been investigated for allergic contact dermatitis diagnosis as well as various cancers; it is currently in phase I trials for cancer[2][8].