A study conducted at The Scripps Research Institute (TSRI) has revealed the science behind the ancient Chinese medicine Chang Shan. Chang Shan is an herbal concoction that has been used to treat fevers that develop from malaria for thousands of years. Now, scientists have uncovered what makes the medicine so successful by looking at a high-resolution picture of its structure.
In the most recent edition of the journal Nature, the researchers explain how an image of a two-headed compound that makes up the active ingredient of Chang Shan is responsible for the medicine’s healing properties. Previously, scientists were aware that this two headed compound, known as halofuginone, which is a derivative of the febrifugine, worked to decrease the power of the immune system. However, until now, no one had discovered just how this drug worked.
By studying the structure of Chang Shan, scientists involved in the study discovered that halofuginone stops a process called aminoacylation, which is essential for organisms to produce the proteins necessary for life. In the paper, the researchers suggest that Chang Shan fights malaria fevers because the halofuginone in the medicine interferes with this process, killing the malaria parasites in the patient’s bloodstream.
Aminoacylation is am important step in creating proteins from DNA during gene expression. During the process, DNA is first transcribed into RNA. The RNA is then translated into amino acids that link to create a protein. Aminoacylation’s roles is to bring free amino acids to the site of translation so they can be linked to the growing strand of amino acids in the protein. Without aminoacylation, no amino acids are brought to the site of translation and no proteins can be made. Since proteins are essential for life, extreme interference of this process can cause death.
Paul Schimmel, who is the Ernest and Jean Hahn Professor and chair of molecular biology and chemistry ay TSRI, believes his research has a profound impact on the study of Chang Shan. “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,” he said. Schimmel, who is also a member of The Skaggs Institute for Chemical Biology at TSRI, worked on the project with a TSRI postdoctoral fellow, Huihao Zhou.
Looking forward, Chang Shan and specifically halofuginone are expected to make a big splash in the medical and pharmaceutical industries. The ancient medicine is already in clinical trials for cancer, and the new high-resolution images will help scientists discover new ways to use the drug to fight numerous diseases.