Download Digging for Ginseng`s Secrets

Digging for Ginseng's Secrets
by Marilyn Davis
Ginseng is on Laura Murphy's mind—and in her tea. Should it be in
yours? It's too soon to say. Ginseng may prove useful against
cancer—someday. This is a road story, not a story about a medical
breakthrough. The destination remains beyond the horizon.
The most valuable thing in Laura Murphy's office, besides her computer, is
a bundle of homely-looking ginseng roots.
Ginseng has been used for centuries in Asian medicine as an aphrodisiac, a
tonic for well-being, and a curative. The root, legendary for the uncanny resemblance it
sometimes bears to the human body, grows slowly and should be several years old before
harvesting. In the United States, where collectors have decimated many wild populations,
growers cultivate ginseng in the woods or commercially farm it, and supplement makers
peddle it as a stimulant and an energy booster.
"Truck stops now have concentrated ginseng extract near the cash registers, where they used
to have the caffeine pills," says Murphy, an associate professor of physiology.
As an herbal remedy, ginseng is largely untested in the West. Because of the extravagant
claims made for many supplements, research into such alternative remedies sometimes is
dismissed as non-mainstream. But Murphy could have the last laugh. Her research may
eventually show that ginseng can help prevent or treat breast and prostate cancer.
Back in the early 1990s, the Illinois Ginseng Growers Association contacted Murphy to inquire
about the pharmaceutical properties of American ginseng (Panax quinquefolium), a different
species from Asian ginseng. "They were wondering why the Asians were buying so much of
their ginseng," she says. U.S. ginseng exports top 1.4 million pounds. The wild-cultivated root
can fetch $300 to $600 per pound; the commercially farmed variety, about $30 per pound.
Murphy had been studying the effects of drugs such as marijuana on reproduction and female
neuroendocrinology. The growers' query, she thought, would make an ideal research project
for some high school students who were working in her lab, courtesy of a School of Medicine
summer program funded by the Howard Hughes Medical Institute.
"There were reports that ginseng has effects on hormones and may itself act like a hormone,
which piqued my interest," she says.
Under Murphy's supervision, the high school students fed male and female rats ground-up
ginseng root in oil, then looked for hormonal changes in those animals compared with rats not
consuming ginseng. In the male rats, one of the things they looked at was libido. To Murphy's
surprise, ginseng "enhanced libido significantly," yet the team found no changes in male sex
hormones. (These findings were later published in Physiology and Behavior.)
Nor did ginseng seem to affect hormones in the female rats, other than to decrease blood
levels of prolactin (a hormone needed for milk production). All of the females reproduced and
nursed normally, and their offspring were normal.
"Ginseng has been used for thousands of years by humans and reported to have very minimal
side effects," says Murphy. "Our rat studies were the first to look for any possible toxicological
effects of high doses in the female during a very vulnerable time [reproduction]. We tested
some really high doses of American ginseng, and it seemed very safe."
Around this same time, Murphy ran across several Korean studies looking at Asian ginseng
and cancer. "The Korean scientists found that Asian ginseng inhibits cancer cell proliferation in
a variety of cancers, such as lung cancer, melanoma, and colon cancer," she says. "They knew
what component in the ginseng was responsible—and this component is not found in American
ginseng."
She wondered if American ginseng might have the same effect on cancer cells. She was also
struck by the fact that the Korean scientists hadn't yet studied any hormone-dependent
cancers, such as breast or prostate cancer.
So she and her undergraduate students exposed cultured human breast cancer cells to a
water extract of American ginseng. They found a nice dose/response relationship: the higher
the concentration of ginseng, the more it slowed down the rate of cell proliferation.
"It doesn't kill the cells, but you can raise the dose to completely inhibit proliferation," says
Murphy. "It arrests the cell in a certain state of development."
These pilot studies, funded by small grants from the School of Medicine, were promising
enough to win Murphy a $295,701 grant from the U.S. Defense Department, which
administers some funds for breast cancer research.
Breast cancers are not all alike. Many tumors have cells with estrogen receptors; they grow
rapidly in the presence of estrogen. Other tumors have cells with no estrogen receptors; their
growth is not spurred by the hormone. So Murphy expanded the petri-dish studies to compare
two different human breast cancer cell lines: one that has estrogen receptors and one that
doesn't. Ginseng inhibited the growth of both types of cells within three to seven days. But it
was about twice as effective with the estrogen-sensitive cells.
"I'm hesitant to say yet whether there's a steroid component" to the response, says Murphy.
Nonetheless, she got a similar result with two types of human prostate cancer cells, one that
is testosterone-dependent and one that
isn't.
Murphy's team next turned to animal
studies. They injected female mice with
human breast cancer cells. Some of the
mice had been drinking regular water
for the previous two weeks; the rest had
been drinking water with 1 percent
ginseng extract. (The human equivalent
would be 2-3 grams of ginseng per
day.) This procedure was continued
after the mice were injected with the
cells.
"This strain of mice has a compromised
immune system that doesn't allow them
to reject foreign tissue," Murphy
explains. "After two weeks you see
tumors form at the site of the
inoculation. There's no difference at first
[between the mice on ginseng and the controls]. But after five weeks, when the tumors are
big enough to start growing their own blood supply, ginseng has an effect."
At the end of the experiment, the tumors in the treated mice were 50 percent smaller than
those in the untreated mice.
If ginseng actually interferes with angiogenesis—the tumor's ability to generate blood
vessels—that is potentially important news. Stopping tumor angiogenesis is one key strategy
for cancer researchers.
But there are other possible explanations. Ginsenosides—the biologically active compounds in
ginseng—are fat-soluble. "My theory is that they accumulate in the fat slowly and that with
everyday usage of even small doses you may accumulate therapeutic levels in your body,"
Murphy says.
That could explain why it takes a few weeks for ginseng to kick in with the tumor-bearing
mice—and why ginseng takes several days to slow the growth of cancer cells in culture,
whereas many drugs have a much faster effect.
"No studies have looked at ginseng metabolism, so we don't know if it does hang around in
the body very long," she adds. "There's so much research we need to do. But Asians who take
ginseng regularly as part of a tonic take it every day. I think that may be important."
A junior in physiology, Jennifer Rice, won a Chancellor's Undergraduate Research Award to
tackle the next step: isolating the compound responsible for Murphy's promising findings. Rice
found it by testing different purified ginsenosides (there are at least 10 in American ginseng)
in cell studies. A ginsenoside dubbed Rc works faster than whole ginseng, checking cancer cell
growth within 48 hours.
"None of the other ginsenosides had any effect," says Murphy. "But with Rc, there's a very
rapid suppression of prostate and breast cancer cell proliferation."
She adds, "Rc is quite different from the ginsenoside in Asian ginseng [that has similar
effects]. It looks like they act through different mechanisms, because the Asian compound
induces cell death and Rc doesn't. I'd like to combine them to see if they have an additive or
synergistic effect on cell proliferation."
Murphy and Rice, who has since graduated and now works as a technician in Murphy's lab, are
trying to determine how Rc acts. " We know so little about it," says Murphy. "Does it stimulate
a receptor? Does it get inside the cell? What's it triggering or turning off in the cell? You have
to have an idea of how [a substance] is acting before you can get into clinical trials."
By measuring the amount of DNA in a cell, an instrument called a flow cytometer can pinpoint
the stage at which the cell's development has been arrested. From these tests, Murphy has
found that Rc acts on the cells when they're relatively young—before they've begun to make
new DNA in preparation for cell division. This narrows her search for the proteins and cellular
mechanisms involved.
Murphy wants to test Rc in animals just as she's tested whole ginseng. But she's run into her
first big obstacle: Rc is very expensive—about $100 per milligram—because it's hard to purify
and no one has synthesized it. Even if she could afford the large quantities needed for animal
studies, they aren't yet available.
"I'm in a corner," she says. She may try to find a chemist with whom she can collaborate to
purify the substance.
In the meantime, there are other avenues to explore. Brian Williams, a student in SIUC's
Medical Education Preparation program, is testing Rc in combination with various
chemotherapy drugs to see if it boosts their effectiveness against cancer cells. Joseph
Gonzalez, a senior in biological sciences, is comparing the effect of different doses of Asian
and American ginseng extract on human prostate cancer cells. And Murphy is beginning to test
whether American ginseng might prevent the onset of breast cancer.
Her team gave female rats ginseng-laced water for 2 weeks. Then they injected the rats with a
carcinogen that, within 6-20 weeks, triggers the development of mammary tumors. The test
rats are continuing to get ginseng in their water. A group of control rats also injected with the
carcinogen are drinking plain water.
Murphy is eager to see how this experiment pans out. Her hunch is that American ginseng will
ultimately "make more sense" as a preventive agent than as a cure, in part because of how
expensive Rc is and in part because it doesn't kill cancer cells.
"Ginseng may turn out to be useful as a food supplement you can take to decrease the
chances of onset of certain types of cancer," she says—just as we may choose to eat soy or
broccoli for their phytoestrogens, antioxidants, and other substances.
Murphy does not suggest that people make a run on their local health food store. Reni Hill, a
junior in physiology, has proved that this is a risk, if nothing else, to the wallet. Hill has been
testing different ginseng supplements on cancer cells and finding that some are duds in terms
of effectiveness. Her work squares with recent reports that some nutrition supplements
contain next to none of the active ingredient touted on the label.
Ginseng has potential health risks, too. It appears to interfere with certain medications, and
some people are allergic to it.
Beyond that, Murphy's findings, though promising, are very preliminary. American ginseng has
not been used in a clinical trial—a rigorous process of testing on humans—to check safety and
effectiveness against cancer. The path from the lab bench to the patient is a long one, and
promising research often dead-ends. But Murphy is sufficiently convinced about ginseng's
safety and its potential that she thinks the research "could move relatively quickly to clinical
trials."
Murphy's work to date, which she presented at the American Society for Cell Biology's national
meeting in December 2000, has attracted the interest of other scientists, some of whom now
also want to test Rc. She welcomes the competition.
"If people want to jump on board and start getting results out, fantastic. The more people do,
the more validated ginseng will become. I think it's important to alter our thinking about
alternative treatments."
For more information, contact Laura Murphy, Ph.D., Dept. of Physiology, at (618) 453-8212.