Artemisinins: pharmacological actions beyond anti-malarial.

Abstract

Artemisinins are a family of sesquiterpene trioxane lactone anti-malarial agents originally derived from Artemisia annua L. The anti-malarial action of artemisinins involves the formation of free radicals via cleavage of the endoperoxide bond in its structure, which mediate eradication of the Plasmodium species. With its established safety record in millions of malarial patients, artemisinins are also being investigated in diseases like infections, cancers and inflammation. Artemisinins have been reported to possess robust inhibitory effects against viruses (e.g. Human cytomegalovirus), protozoa (e.g. Toxoplasma gondii), helminths (e.g. Schistosoma species and Fasciola hepatica) and fungi (e.g. Cryptococcus neoformans). Artemisinins have demonstrated cytotoxic effects against a variety of cancer cells by inducing cell cycle arrest, promoting apoptosis, preventing angiogenesis, and abrogating cancer invasion and metastasis. Artemisinins have been evaluated in animal models of autoimmune diseases, allergic disorders and septic inflammation. The anti-inflammatory effects of artemisinins have been attributed to the inhibition of Toll-like receptors, Syk tyrosine kinase, phospholipase Cγ, PI3K/Akt, MAPK, STAT-1/3/5, NF-κB, Sp1 and Nrf2/ARE signaling pathways. This review provides a comprehensive update on non-malarial use of artemisinins, modes of action of artemisinins in different disease conditions, and drug development of artemisinins beyond anti-malarial. With the concerted efforts in the novel synthesis of artemisinin analogs and clinical pharmacology of artemisinins, it is likely that artemisinin drugs will become a major armamentarium combating a variety of human diseases beyond malaria.

• Authors: Wanxing Eugene Ho, Hong Yong Peh, Tze Khee Chan, W S Fred Wong
• Journal: Pharmacology & therapeutics (Pharmacol Ther) Vol. 142 Issue 1 Pg. 126-39 (Apr 2014) ISSN: 1879-016X [Electronic] England
• PMID: 24316259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antifungal Agents
• Antimalarials
• Antineoplastic Agents
• Antiparasitic Agents
• Antiviral Agents
• Artemisinins

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antifungal Agents (pharmacology)
• Antimalarials (pharmacology)
• Antineoplastic Agents (pharmacology)
• Antiparasitic Agents (pharmacology)
• Antiviral Agents (pharmacology)
• Artemisinins (pharmacology)
• Humans