June 2011 by Wendy Zukerman
A hooked herb, root extract and a dash of bark – it may sound like a witches’ brew, but these compounds could provide treatments for diseases that have so far foiled western doctors, such as Parkinson’s and irritable bowel syndrome. For over 2000 years Chinese doctors have treated “the shakes” – now known as Parkinson’s disease – with gou teng, a herb with hook-like branches.
Early this year, 115 people with Parkinson’s were given a combination of traditional Chinese medical herbs, including gou teng, or a placebo for 13 weeks. At the end of the study, volunteers who had taken the herbs slept better and had more fluent speech than those taking the placebo. Gou teng appears to stabilise symptoms, says Li Min, a traditional Chinese doctor at Hong Kong Baptist University. Now, Li and her colleagues have figured out how it might work.
Parkinson’s symptoms, such as muscle tremors, slowness of movement and rigidity, are caused by the progressive destruction of brain cells that produce dopamine. Previous work has suggested that an abundance of a protein called alpha-synuclein may be to blame. Current treatments aim to boost levels of dopamine, which only partly alleviates symptoms and does not affect the protein clusters. It is thought that clumps of alpha-synuclein accumulate because brain cells cannot remove them through autophagy – a type of programmed cell death. Mice without the genes needed for autophagy quickly develop Parkinson’s-like symptoms.
According to Li, autophagy is the only known process that gets rid of abnormal proteins within cells. “Enhancing this pathway may be key to treating Parkinson’s,” she says. Li’s team screened gou teng for its active compounds and tested which of these compounds increase the rate of autophagy and remove alpha-synuclein. To do this, the team added the compounds to human nerve cells and fruit flies that had been genetically modified to develop alpha-synuclein clusters.
One of the compounds, an alkaloid called isorhy, induced autophagy for alpha-synuclein at a similar rate to a drug called rapamycin. Rapamycin is normally used to suppress the immune system in transplant patients, but has recently been touted as a promising candidate for Parkinson’s treatment because it prevents nerve cell death in flies with a Parkinson’s-like disease. However, because rapamycin depresses the immune system, it would have serious side effects for people with Parkinson’s. Gou teng, meanwhile, has been taken for centuries with no apparent side effects. Further testing found that isorhy activates autophagy through a different pathway to rapamycin, which may explain why it does not affect the immune system in the same way. Li, who recently presented her results at theKeystone Symposia on Molecular and Cellular Biology in Whistler, British Columbia, Canada, will begin trials of Isorhy in rodents later this year.
Herbs for the gut
Meanwhile, Zhaoxiang Bian, also at Hong Kong Baptist University, is developing a drug called JCM-16021 for irritable bowel syndrome (IBS) using seven herbal plants and based on a Chinese formulation called Tong Xie Yao Fang, used to treat IBS since the 1300s. IBS affects up to 20 per cent of people, causing abdominal pain, constipation and diarrhoea. “They feel really rotten, and it’s sufficiently severe for people to take time off work,” says John Furness at the University of Melbourne, Australia. Stress management can help symptoms, but there is no effective medicine to treat it.
In 2007, Bian gave 80 people with IBS either JCM-16021 with Holopon – a drug that interrupts nerve impulses in the parasympathetic nervous system responsible for digestion – or Holopon alone. After eight weeks, 52 per cent of those given JCM-16021 with Holopon reported reduced IBS symptoms, compared with 32 per cent of those given Holopon alone.
IBS is partly caused by high levels of serotonin in the gut. Last year, Bian found that giving JCM-16021 to rats with IBS-like symptoms broke down serotonin in their bowel faster than normal, reducing their discomfort. His team has since isolated several active compounds in JCM-16021 that block serotonin’s activity in the rat gut, including magnolol, a herb taken from the bark of Magnoliae officinalis.
Root of relief
This month, Keiko Lee at Juntendo University in Tokyo, Japan, found that paeoniflorin, a root extract used in JCM-16021, acts as an analgesic in rats, inhibiting adrenaline receptors in the spine. Bian is now combining the active extracts of JCM-16021 to develop a new drug that attacks IBS from different angles. Unlike conventional approaches, which target only one aspect of the disease, he believes the combination drug will be more effective. “I think it is a very rational way to go,” says Furness, but warns that combination drugs usually take longer to gain approval because of the greater-than-usual possibility of unexpected side effects. But because these compounds have a long history of being safe for human consumption, it is hoped they will be approved faster, says Li. “In the past the pharmaceutical industry didn’t put much effort into traditional Chinese medicine,” says Jing Kang, a biochemist at Harvard Medical School in Boston. “In the past few years this has been changing. More people are paying attention.”
Journal references: gou teng and Parkinson’s: Parkinson’s Disease, DOI: 10.4061/2011/789506; rapamycin and Parkinson’s: Nature Neuroscience, DOI: 10.1038/nn.2372; JCM-16021 and serotonin: World Journal of Gastroenterology, DOI: 10.3748/wjg.v16.i7.837; paeoniflorin and pain relief:European Journal of Pain DOI: 10.1016/j.ejpain.2011.04.011