OHSU

OHSU Examines Herb's Effects On Diabetic Neuropathy

02/23/11  Portland, Ore.

Positive results in 2005 preclinical study prompt trial of Ayurvedic botanical

A 2005 OHSU study showing an herbal supplement speeds recovery in an animal model of nerve damage has triggered a clinical trial to determine if the compound has the same effect in humans suffering from diabetic neuropathy.

Oregon Health & Science University researchers have launched a Phase II, National Institutes of Health-funded study of an extract of Centella asiatica, a botanical traditionally used as a nerve tonic in the ancient Hindu system of healing known as Ayurveda. They will follow 60 subjects with diabetic neuropathy who will be given the herbal extract or placebo for a year in the randomized, double-blind trial expected to last through 2010.

The trial's principal investigator, Jau-Shin Lou, M.D., Ph.D., associate professor of neurology in the OHSU School of Medicine, said those with diabetes have some options to treat symptoms like numbness, pain and weakness, but there is no way to promote regrowth of the damaged nerves. This means these people will have these symptoms as long as they have diabetes.

"Physicians really don't have a good way of preventing diabetic neuropathy other than trying to control blood sugar," said Lou, director of the OHSU's EMG Laboratory. "This drug, if effective, will give us a treatment for diabetic neuropathy on top of regular sugar control."

Bethany Klopfenstein, M.D., a diabetologist at the OHSU Diabetes Center, serves as a co-investigator of the study. Klopfenstein, an assistant professor in the OHSU School of Medicine, said "neuropathy is one of the most disabling complications of diabetes, and also the most difficult to treat. The medications currently available can dull the symptoms, but also have side effects that can be difficult to tolerate. In addition, once neuropathy is present, we have no way to reverse the damage. The preliminary studies suggest Centella asiatica may lead to recovery of damaged nerves."

The trial was prompted by results from an OHSU study on laboratory rats that lost use of their hind legs due to sciatic nerve damage. The results, published in 2005 by OHSU's Bruce Gold, Ph.D., associate professor of neurology, and Amala Soumyanath, Ph.D., associate professor of neurology an expert on medicines derived from botanicals, in the Journal of Pharmacy and Pharmacology, showed that Centella asiatica, sometimes sold as gotu kola, regenerated nerve cells in the rats when given an extract of the herb in their drinking water.

Soumyanath said the rats tend to recover spontaneously from their disability without Centella asiatica over three weeks. But things change after they consume the extract.

"We found if you put this extract in their water, they just recover a whole lot faster," she said. "They start to recover virtually from day four, and they recover so much of their function by day 18, it's a statistically significant difference."

Klopfenstein, Soumyanath and Lou hope to see similar results in humans. The trial will use a blend of Centella asiatica's three active ingredients - asiatic acid, madecassic acid and asiaticoside - known collectively as Centella asiatica selected triterpenes (CAST), prepared by Indena, a manufacturer of high quality botanical extracts.

"What we tested in the rats was actually a crude extract (of Centella asiatica), which means it had a whole mishmash of things, including these compounds," Soumyanath said. "We did test these compounds on nerve cells, and we found they all had the same effect as the crude extract, suggesting that these three components were responsible, to a large extent, for the activity of the extract."

Significantly, these three compounds also have been shown to improve "microcirculation" - the flow of blood through the body's smallest vessels, such as arterioles, capillaries and venules - in other studies in humans.

"We believe it's kind of double-whammy for those with diabetic neuropathy," Soumyanath said. "It improves your microcirculation and it helps your nerves regenerate. I mean, if it works, that would be great."

Centella asiatica is a slender plant with fan-shaped leaves that is found primarily in the swampy regions of India, Madagascar and other tropical climates, including the southern United States. It is often prepared as a tea and can be dried for use in capsules; dietary supplement retailers describe it as an energy and vitality booster that promotes circulation to the brain and throughout the body. The validity of those claims is uncertain, and the research at OHSU is aimed at clarifying the facts surrounding this and other botanical therapies.

Diabetic neuropathy occurs when poor circulation caused by high glucose levels in diabetes damages nerve cells. According to the National Institutes of Health, about half of diabetes sufferers have some form of neuropathy, but not all with neuropathy have symptoms. Peripheral neuropathy, which affects the arms and legs, is the most common type of diabetic neuropathy.

Lou's laboratory specializes in finding and studying damage to large and small nerve fibers, the thin, branch-like threads through which signals are sent between the cell body and its terminal. Typically, weakness and numbness occur if the large fibers are damaged, while burning and stabbing sensations result when small fibers are damaged.

"It's very disturbing to a lot of diabetic patients," Lou said. "In diabetic neuropathy, both of these fiber types can be affected. In our laboratory, we have specific procedures to test large fibers and small fibers so we can document the changes of these nerve functions over the time of this drug trial to see if CAST can slow down the progression of neuropathy."

Doing so "can improve the patient's quality of life because of reduced pain and burning, and it can preserve their motor function so they can begin functioning without losing muscle strength," he added.

Klopfenstein, Soumyanath and Lou hope the trial, if successful, leads to similar therapies for other disorders of both the peripheral and central nervous systems. In fact, in a study co-authored by Soumyanath and presented to the Society for Neuroscience in late 2005, Centella asiatica appeared to normalize the behavior of mice bred to express a protein mutation that causes Alzheimer's-like symptoms.

"At some point, we may also want to see whether it can actually penetrate the central nervous system, in which case there are a whole other bunch of diseases where you've got nerve degeneration," Soumyanath said. "And there are many other conditions, like paralysis, and other causes of neuropathy, and we would like to study this same herb in those."

One such cause of neuropathy is alcohol abuse, Lou said. "Alcoholic neuropathy is very common," he said. "If you drink too much, it damages your nerves. It's the same type of neuropathy you see in diabetics. It's a huge population."

For more information on the clinical trial, contact Grace Arnold, research coordinator for this study, at 503 494-4987 or arnoldg@ohsu.edu.

OHSU STATEMENT: Dr. Soumyanath is the director of research and development for Oregon's Wild Harvest, which was involved in the preparation of investigational products used in this research. This potential conflict of interest has been reviewed and managed by OHSU.

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