parthenolide

Parthenolide is a natural product, a sesquiterpene lactone identified as the principal bioactive constituent of feverfew (Tanacetum parthenium). It belongs to the germacranolide class and features an α-methylene-γ-lactone group that acts as a Michael acceptor, enabling covalent modification of thiol groups in proteins and contributing to its biological activity. Parthenolide occurs mainly in feverfew leaves and flowering tops and has been isolated as a major constituent of several Tanacetum species.

In pharmacology, parthenolide is best known for anti-inflammatory effects, largely attributed to inhibition of the NF-κB signaling pathway. By covalently modifying cysteine residues in components of the NF-κB axis, it reduces transcription of pro-inflammatory genes. It also shows cytotoxic activity in various cancer cell lines and has been studied for potential anti-tumor and anti-angiogenic properties in preclinical models. Because of its reactivity, parthenolide can affect multiple cellular targets, which complicates therapeutic development and contributes to toxicity concerns.

In medical use, feverfew has long been used in traditional medicine to prevent migraine. However, parthenolide itself is not an approved drug, and clinical use relies on whole-plant extracts or standardized feverfew products, with variable parthenolide content. Research continues into derivatives and formulations to improve solubility, selectivity, and safety.

Safety considerations include potential allergic reactions, mouth ulcers, gastrointestinal upset, and interactions with anticoagulants or other medications. Standardized dosing is challenging due to variability in parthenolide content in herbal preparations.