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Ancient Chinese Herb's Molecular Secrets Offer New Autoimmune Disease Therapies

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Two thousand-year-old Chinese herbal remedy could inspire new therapies for autoimmune diseases, according to a study published online on February 12, 2012, in Nature Chemical Biology. Researchers from the Harvard School of Dental Medicine have uncovered the molecular secrets behind the ancient herb's powers.

The team discovered that halofuginone HF, derived from a bioactive ingredient found in the root extract commonly known as chang shan, targets a stress-response pathway to block the development of harmful immune cells called Th17 cells. These cells are implicated in diseases like inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis and psoriasis.

Chang shan prevents autoimmunity without compromising overall immunity, sd Malcolm Whitman, professor of developmental biology at Harvard School of Dental Medicine and senior author on the study. This compound may lead to novel therapeutic approaches for a range of autoimmune disorders.

Our findings highlight how understanding the molecular mechanisms of traditional herbal medicine can illuminate physiological regulation and provide new avenues for treating diseases, added Tracy Keller, first author in Whitman's lab.

The interdisciplinary research team involved Harvard-affiliated Massachusetts General Hospital among other institutions. The study builds on prior research that showed HF reduces scarring from conditions like scleroderma tightened skin, multiple sclerosis, tissue damage from cancer progression and more.

Keller explned that the initial discoveries were made after scientists found HF reduced multiple sclerosis in a mouse model at minute dosessuggesting it selectively inhibits autoimmune pathology without suppressing the immune system as a whole. Further analysis revealed that HF triggers activation of a novel signaling pathway known as the amino acid response AAR.

Scientists recently discovered this pathway plays roles in immune regulation and metabolic signaling, showing potential to ext lifespan and delay age-related diseases when animals are fed restricted diets.

The AAR pathway acts like a cell's conservation mechanism, Whitman explned. When a cell senses scarce amino acids needed for protein synthesis, the pathway inhibits inflammatory signals because inflamed tissues consume large amounts of proteins.

To investigate how HF activates the AAR pathway, researchers focused on basic biological processes that translate DNA codes into amino acid chns. They were able to hone in on prolinea specific amino acidand found restricting its intake activates the AAR response and impacts immune regulation.

While scientists do not yet fully understand why limiting certn amino acids affects disease responses or how restricting proline inhibits Th17 cell production, the findings suggest potential for further research into this area. The study demonstrates that the AAR pathway is an interesting target for drug development and highlights halofuginone's potential in both therapeutic uses and as a tool to advance understanding of its mechanism.

This research was funded by the National Institutes of Health and supported by a Harvard Technology Accelerator Award.

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