Study Suggests Compound in Chinese Root Extract Effective In Treating MS, Other Autoimmune Diseases

Herbal medicine has been used since ancient times to treat certain diseases and ailments. Scientists are closely looking into the molecular mechanism behind some remedies used in traditional herbal medicine to further determine their effectiveness in treating certain diseases. Researchers have closely looked into a 2,000 year-old Chinese herbal remedy for malaria and discovered that it can also be used to treat many autoimmune disorders such as MS as well.

Researchers from the Harvard School of Dental Medicine have looked into the molecular mechanism behind a compound known as halofuginone, a compound taken from a root extract known as Chang Shan, a traditional Chinese herbal remedy to treat malaria. The researchers found out that halofuginone or HF triggers a stress-response pathway in the body that blocks the production of immune cells called Th17, which has previously been implicated in a variety of autoimmune disorders.

According to Malcolm Whitman, professor of developmental biology at the Harvard School of Dental Medicine and a senior author of the said study, “HF prevents the autoimmune response without dampening immunity altogether. This compound could inspire novel therapeutic approaches to a variety of autoimmune disorders.”

The said study also involved an interdisciplinary team of researchers hailing from the Massachusetts General Hospital and other centers. “This study is an exciting example of how solving the molecular mechanism of traditional herbal medicine can lead both to new insights into physiological regulation and to novel approaches to the treatment of disease,” adds Tracy Keller, an instructor in Whitman’s lab and the first author of the paper. The findings are published in the February 12 online edition of Nature Chemical Biology.

Th17 cells have been implicated in various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel syndrome, multiple sclerosis and psoriasis. Keller and colleagues have reported in 2009 that HF protects against the wayward Th17 cells without affecting the other beneficial immune cells. Low doses of HF were able to reduce multiple sclerosis symptoms in mouse models of the said disease. HF was able to selectively suppress this harmful portion of the immune system without affecting the other more important parts. The researchers also further discovered that HF was also able to turn on those genes that are involved in a newly discovered pathway that’s known as the amino response pathway or AAR.

It is only recently that researchers have fully determined the function of the Aar pathway in immune regulation as well as metabolic signaling. It is the AAR that lets the cells know when it is the time to preserve essential resources in the body.

The researchers investigated how HF is able to activate the AAR pathway. They were able to discover that a type of amino acid called proline that is incorporated into proteins. They further discovered that HF targets and inhibits a particular enzyme essential in incorporating proline into proteins. When this happens, the AAR response it triggered, leading to the therapeutic effects of HF.

When supplemental proline is provided, the effects of HF are reversed, thereby establishing that HF specifically affects proline incorporation in proteins. Supplementation of other amino acids yielded no such effects on HF.

The researchers believe that using HF seems to mimic the deprivation of proline on a cellular level which activates the AAR response which then affects immune regulation. Researchers might require further studies in order to understand how proline is able to inhibit Th17 cell production.


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