Sesquiterpene lactones: adverse health effects and toxicity mechanisms

Crit Rev Toxicol. 2013 Aug;43(7):559-79. doi: 10.3109/10408444.2013.813905.


Sesquiterpene lactones (STLs) present a wide range of biological activities, mostly based on their alkylating capabilities, which underlie their therapeutic potential. These compounds are the active constituents of a variety of plants, frequently used as herbal remedies. STLs such as artemisinin and its derivatives are in use as first-line antimalarials while others, such as parthenolide, have recently reached cancer clinical trials. However, the toxicological profile of these compounds must be thoroughly characterized, since the same properties that make STL useful medicines can also cause severe toxicity. STL-containing plants have long been known to induce a contact dermatitis in exposed farm workers, and also to cause several toxic syndromes in farm animals. More recently, concerns are been raised regarding the genotoxic potential of these compounds and the embryotoxicity of artemisinins. A growing number of STLs are being reported to be mutagenic in different in vitro and in vivo assays. As yet no systematic studies have been published, but the genotoxicity of STLs seems to depend not so much on direct DNA alkylation as on oxidative DNA damage and other partially elucidated mechanisms. As the medicinal use of these compounds increases, further studies of their toxic potential are needed, especially those focusing on the structural determinants of genotoxicity and embryotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / toxicity*
  • Antimalarials / administration & dosage
  • Antimalarials / toxicity
  • Artemisinins / chemistry
  • Artemisinins / toxicity*
  • Cardiovascular System / drug effects
  • Cardiovascular System / pathology
  • Central Nervous System / drug effects
  • Central Nervous System / pathology
  • DNA Damage
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / pathology
  • Insecta / drug effects
  • Insecta / metabolism
  • Kidney / drug effects
  • Kidney / pathology
  • Lactones / chemistry
  • Lactones / toxicity*
  • Liver / drug effects
  • Liver / pathology
  • Mammals
  • Plant Extracts / chemistry
  • Plant Extracts / toxicity*
  • Plant Leaves / chemistry
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / toxicity
  • Skin Diseases / chemically induced
  • Skin Diseases / pathology
  • Teratogenesis / drug effects


  • Anti-Infective Agents
  • Antimalarials
  • Artemisinins
  • Lactones
  • Plant Extracts
  • Sesquiterpenes
  • parthenolide
  • artemisinin