helenalin

Helenalin is a sesquiterpene lactone that occurs in several Arnica species, notably Arnica montana (mountain arnica) and Arnica chamissonis. It is among the most bioactive and toxic constituents of arnica extracts, typically present alongside related helenanolides such as dihydrohelenalin.

Chemically, helenalin is a germacranolide-type sesquiterpene lactone characterized by an α-methylene-γ-lactone moiety, a reactive Michael acceptor that readily forms covalent bonds with thiol groups in proteins. This reactivity underpins both its pharmacological effects and its toxicity.

Biological activity: In vitro, helenalin inhibits the transcription factor NF-κB by covalently modifying the RelA/p65 subunit, preventing DNA binding and transcription of NF-κB target genes. It also shows cytotoxic effects against several cancer cell lines at low micromolar concentrations, though issues of selectivity and in vivo efficacy remain active research areas. In plants, helenalin is part of a chemical defense system against herbivores and pathogens.

Safety and regulation: Due to its alkylating reactivity, helenalin can cause skin irritation and dermatitis on contact. For this reason, many topical arnica preparations are processed to reduce helenalin content; oral ingestion of helenalin-containing products is discouraged. It is not approved as a pharmaceutical drug, and arnica products are typically marketed for mild topical use with caution.