December 24, 2012
Researchers Unlock The Secret Of Ancient Herbal Malaria Cure
redOrbit Staff & Wire Reports - Your Universe Online
For over a millennium the Chinese have used an herb known as Chang Shan to treat fevers associated with malaria. While its effectiveness in treating the disease has long been confirmed by modern medicine, its exact function has remained mystery. However, in a recent study, scientists at The Scripps Research Institute (TSRI) say they have uncovered the molecular mechanism that gives this ancient homeopathic drug its healing properties.The researchers say the critical component in Chang Shan is a molecule called halofuginone, and by analyzing its molecular structure they have discovered how it interacts with the immune system to ward off the tiny parasites associated with malaria.
Halofuginone is already being tested in clinical trials as a treatment for cancer. However, the researchers now say the biochemical´s unique molecular structure may make it useful as a multipurpose template compound for treating a variety of disease, such as malaria.
According to Paul Schimmel, the study´s lead researcher and Chair of Molecular Biology and Chemistry and member of The Skaggs Institute for Chemical Biology at TSRI, the compound halofuginone works by disrupting an important step in the production of proteins known as aminoacylation — a step that is critical to essentially all forms of life.
In order for proteins to be produced in any organism, they must first be decoded from DNA and translated into amino acids, the building blocks that make up proteins. Critical to this process is a family of molecules known as transfer RNAs (tRNA), which help transport these amino acid building blocks around so they can be added to proteins that are being synthesized. However, before tRNA can shuttle around amino acids, they must first be able to latch onto the tiny molecules. And it is here halofuginone comes into the picture.
At the most basic level, the process of aminoacylation involves four key players: a tRNA molecule, an amino acid, an energy providing molecule called ATP, and an enzyme called aminoacyl-tRNA synthetase that helps attach the amino acid to the tRNA. If any one of these molecules isn´t functioning properly, the production of vital proteins breaks down.
The researchers have discovered the halofuginone molecule acts by blocking the activity of the aminoacyl-tRNA synthetase enzyme in the parasites that cause malaria. Like a monkey wrench thrown into the cogs of a machine, the herbal chemical compound lodges itself into the structure of the enzyme and prevents it from helping the tRNA and amino acid connect with each other. And if the tRNA can´t latch onto the amino acid, then it can´t carry it to the site where the new proteins are being constructed, meaning protein production is disrupted, causing the organism to die.
“Our new results solved a mystery that has puzzled people about the mechanism of action of a medicine that has been used to treat fever from a malaria infection going back probably 2,000 years or more,” said Schimmel
The team´s article, titled “ATP-Directed Capture of Bioactive Herbal-Based Medicine on Human tRNA Synthetase,” was coauthored by Schimmel´s colleagues Huihao Zhou, Litao Sun and Xiang-Lei Yang, and appears in the December 23 edition of the journal Nature.