March 31, 2010 -- Most Americans have used herbal drugs during the past year, even though in nearly all cases there is no clear scientific evidence that they work. Now, an international team of scientists has found a way to collect that evidence, and even determine which components of very complex compounds are doing the work, and which aren't.
The effort is lead by Yuan Luo, an associate professor in the University of Maryland's department of pharmaceutical science, who grew up in China where many herbal remedies that are used today have been used for thousands of years.
"This provides the first step to find, from all of the hundreds of compounds in herbs, which ones have potential for medicinal purposes. And you can do this very quickly and efficiently," said Laura Dosanjh, a graduate student and coauthor of a paper describing the research in the journal PLoS ONE.
The first results suggest that two very popular herbs, cinnamon and ginseng, can potentially extend lifespan. But that's based on research with the star of this show, a transparent earthworm, C. elegans, which has become a real workhorse in labs around the world because of genetic similarities with higher animals, including humans.
Few Studies on Herbs Because No Profit Motive
"Nobody is saying this will increase the lifespan in humans, because that research has never been done," Luo said in a telephone interview. But the results in C. elegans are tantalizing. Cinnamon alone was found to increase the lifespan of the worm by up to 14.5 percent.
Luo's technology could help answer questions that have bedeviled health professionals for years. Herbs are medicines, although they have never gone through the clinical trials required for approval by the Food and Drug Administration.
Those trials are very expensive, and pharmaceutical companies that normally pay for the trials have no incentive to do so for herbs that are already on the market because they cannot be patented. Thus, no profit motive leads to very little evidence that any of them work.
What is left is anecdotal evidence from people who have used them and claim to have benefited. That is what has kept the drugs so popular in China for many generations, said Luo, who came to the United States for graduate school and never left.
Anecdotal Evidence Boosts Herbal Drugs in China
"When people are weak or they are old they drink green tea and they feel better," she said. "That's why they think this is good. It's not experimental evidence."
When she set out to fill that evidentiary gap a few years ago she turned to C. elegans, a tiny worm, about the size of a human eyelash, that has played a critical role in genetics research. Sydney Brenner, who won the Nobel prize in 2002 for his work with the worm, introduced C. elegans to the laboratory in 1974, and the rest, as they say, is history.
This remarkable worm has 20,000 genes, many of which perform the same functions in both the worm and humans, so its arrival gave researchers a chance to find out which genes were responsible for which activities in the worm, and as it turned out in many cases, in humans as well.
The worm has a lifespan of only two to three weeks, so it is possible to carry out experiments in a brief period of time. It is fairly easy to disable various genes, thus making it easier to determine their functions, and the worms can be frozen and stored, then awakened to do their job.
Herbs Extend Life of a Worm, But What About Humans?
So a researcher who needs a worm with one gene silenced can go to the worm store and buy a bunch. It's really that easy.
It also turns out to be fairly easy to manipulate the lifespan of the worm. Researchers at Emory University, for example, found they could add 50 percent to the longevity of C. elegans with drugs designed to eliminate free radicals, toxic byproducts of metabolism. And scientists at the Howard Hughes Medical Institute found they could extend the lifespan by about 30 percent with a drug used to treat depression.
But C. elegans hit center stage a few years ago when scientists announced that resveratrol, a natural compound, also extended its lifespan. Resveratrol is found in red wine, so it was a very popular discovery.
The fact that the worm's lifespan can be stretched so much may not bode well for similar results in humans. We are living longer these days, but not all that much, despite centuries of medical progress. We may be similar to a worm, but we're a tad more complicated.
Cinnamon Is Among Most Potent Antioxidant Herbs
And many herbs, it turns out, don't do much for C. elegans either. Luo and her team, which includes researchers in Korea, tested several herb-based supplements, including green tea, breaking them down into their component parts so they could analyze all the herbs individually, and in concert with other herbs.
"Among all individual herbs tested, only two herbs, Panax ginseng root and Cinnamomum (cinnamon) cassia bark significantly extended the life span in C. elegans," they wrote in their study.
They also found that cinnamon is a star performer.
"A systematic evaluation of more than 30 herbs found that cinnamon is among the most potent antioxidant herbs," they reported.
The research also revealed that both of those herbs reduced the expression of amyloid, a "hallmark in the human brain of pathological development of Alzheimer's disease."
By turning to the tiny earthworm, Luo and her colleagues have established a way to examine even complex compounds to determine which components are essential. She explained that in some cases a certain "synergism" is required, so some herbs might detoxify while others help cells fight off cancer, for example. If herbs are removed without understanding their role, the drug might be weakened.
Perhaps the biggest concern among medical professionals, however, is not over whether the herbs do good. It's whether they do damage instead.
In the absence of clinical trials that determine the efficacy of drugs - even if they cannot be patented - many questions will persist. And it is still not known if herbs that work for an earthworm also work for humans.
But we are, after all, more similar than anyone thought just a few years ago.