Helenalin – a toxic sesquiterpene lactone – University of Copenhagen

NaToxAq > Toxin of the week > Helenalin

17 December 2018

Helenalin – a toxic sesquiterpene lactone

Natural toxin

Intensely poisonous to human and other mammals, causing paralysis of voluntary and cardiac muscles and fatal gastroenteritis. It suppresses the activation of an immune defense mediator and is toxic.

Figure: Arnica montana (a) and H. autumnale (b) contains Helenalin, and (c) the chemical structural of sesquiterpene lactone Helenalin. Click image for an interactive 3D model of helenalin.

Helenalin is naturally occurring sesquiterpene lactones extractable from many Helenium spp. (e.g. in sneezeweed, H. autumnale) and many other Compositae (e.g., Arnica montana, Anaphalis and Gaillardia spp.), which exhibits potent anti-inflammatory and anti-tumor effect. It is classified as pseudoguaianolide sesquiterpene lactones consisting of two reactive groups; α-methylene-γ-butyrolactone (moiety characteristic of all sesquiterpene lactones) and a reactive α,β-unsubstituted cyclopentenone group. Helenalin can undergo a Michael-type addition with proteins/peptides via thoil groups (strong nucleophile), resulting in their alkylation. Thus, it can disrupt the molecule’s biological function and consequently affects the proper function of the cell and, thereby, influences the cell functionality. Therefore, alkylation of critical tissue sulfhydryl groups is thought to provide the biochemical basis for helenalin toxicity.

Helenalin is a potent stimulator of mass cell degranulation. It can cause contact dermatitis, muscle paralysis, gastroenteritis, cardiac and liver damage. It shows cytotoxic and antileukaemic activities. It is toxic to fish and insects. Also, it shows activity against several fungi pathogenic to human, as well as molluscicdal activities. After consumption of 2.5 g/body weight, the death of cattle, sheep and goats has been reported.

CAS NO: 6754-13-8
SMILES: CC1CC2C(C(C3(C1C=CC3=O)C)O)C(=C)C(=O)O2

References:

  • Harborne JB, Baxter H and Moss GP (1999). Phythochemical dictionary: a hand book of bioactive compounds from plants. Second edition, TJ International Ltd, Padstow, UK.
  • Zwicker P, Schultze N, Niehs S, Albrecht D, Methling K, Wurster M, Wachlin G, Lalk M, Lindequist U, Haertel B (2017).  Differential effects of Helenalin, an anti-inflammatory sesquiterpene lactone, on the proteome, metabolome and the oxidative stress response in several immune cell types, Toxicology in Vitro 40: 45–54.
  • Berges C, Fuchs D, Opelz G, Daniel V, Naujokat C (2009).  Helenalin suppresses essential immune functions of activated CD4+ T cells by multiple mechanisms, Molecular Immunology 46: 2892–2901.

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