Research will begin to test the plant
against cancer and its symptoms

Thursday, June 19, 2001
GEORGE F. LEE / GLEE@STARBULLETIN.COM
Research physician Dr. Brian Issell displayed the CAT
scans of patients being monitored in a study on the
effects of medications from the noni plant.The Noni plant, used in traditional healing throughout Polynesia, has become one of the most popular complementary treatments worldwide for all kinds of diseases.

Yet, there is no evidence that the plant is useful medically, says Dr. Brian Issell, clinical sciences program director at the Cancer Research Center of Hawaii.

He has received a National Institutes of Health grant of $170,000 per year for two years to conduct the first scientific study of Noni in humans.

Noni, extracted from the Indian mulberry plant, has been used for more than 1,000 years in traditional healing practices of native Hawaiians and other Pacific Islanders and Asian populations.

However, it’s the least known of the five most commonly used complementary medicines, says Nina Etkin, medical anthropologist who heads the University of Hawaii anthropology department.

The others — aloe, garlic, ginseng and lemongrass — are very well characterized chemically and their medical uses are well-documented, she said.

Etkin looked at the plants as part of a study on use of complementary medicines in Hawaii published in 1999 in “Economic Botany.”

She said she became interested when Noni emerged as “a prominent phenomenon” here in the early 1990s. “At one point it was very expensive. People were using Noni for virtually everything — cancers, diabetes, cardiovascular disease, colds, infections and wounds.”

Noni was used sparingly in traditional Hawaiian medicine, and only topically on wounds and skin disorders, never internally, she said. So, she was curious about the plant’s dramatic reputation for medical treatments.

She found that, driven by commercial ventures and advertising, “it really took fire and now is very popular worldwide,” she said. “But, as many of these complementary and alternative medicines, it was virtually untested. Its reputation preceded demonstrated scientific merit.”

Issell said he was prompted to look at Noni because many people say it is helping them. Some studies have shown it has some effect on cancer cells, but it hasn’t been studied scientifically in people, he said.

“We want to see if it works or not, and how good the compounds are,” he said. “We want to make sure it helps people more than harms them.”

He plans to begin research early next month after the Noni capsules arrive. A mainland company is producing them with freeze-dried extract from Hawaii-grown plants, he said.

Cancer patients for whom standard treatments haven’t worked, or who haven’t had any treatments, and meet other criteria will be recruited to take the capsules.

The first phase is to figure out what doses can be tolerated and if there is any evidence that Noni alleviates a patient’s cancer symptoms or causes the cancer to shrink, he said.

Patients will be evaluated regularly, with measurements of the tumors and other things associated with cancer, such as fatigue, depression and general quality of life, he said.

The next stage will be to look at particular cancers and identify any ingredients in Noni that are more powerful as anti-cancer agents, he said. A traditional way of preparing Noni in Hawaii is to seal the fruit in a glass jar with water and leave it in the sun to ferment, making juice to drink.

Issell said: “The smell is worse than the taste. When you taste it, it’s not as bad as you think it would be. It’s a little sour, a little bitterness to it.”

Putting it in capsules is not so much to hide the taste but to be consistent, he said.

He said he’s excited because his Noni research is “just the very first step at looking at a number of botanicals, plant extracts, that have been used in traditional healings of our multicultural population here.”

Issell has been involved in developing other anti-cancer drugs from plants, such as those from the periwinkle plant. “Two very powerful drugs actually cured patients with otherwise incurable cancer,” he said.

For more information about the Noni study, call the clinical trials unit at 1-808-586-2979. For information about complementary and alternative treatments for cancer, call the Cancer Information Service, 1-800-4-CANCER.

© 2001 Honolulu Star-Bulletin
http://starbulletin.com

T. Hiramatsu, M. Imoto, T Koyano, K. Umezawa Cancer Letters 73 (1993) 161-166

In this study, a team of Japanese researchers studied the effect of over 500 extracts from tropical plants on the K-ras-NRK cell (a pre cursor to certain types of cancer). The compound, damnacanthal, found in the Morinda Citrifolia (Noni), was found to be an inhibitor of Ras function. The research: Ras cells were seeded into 96 plates and incubated at 33 degrees centigrade for 24 hours. The Noni plant extract was added and the cell morphology was examined every day for five days.

The Ras function was inhibited by the injected plant extract. This same compound has been found to inhibit the Epstein-Barr virus early-antigen activation. The extract from the Morinda Citrifolia was found to be most effective in inhibiting Ras function among the 500 tested extracts.

Hirazumi, E. Furusawa, Phytother Res. 1999 Aug;13(5):380-7.

The fruit juice of Morinda citrifolia (noni) contains a polysaccharide-rich substance (noni-ppt) with antitumour activity in the Lewis lung (LLC) peritoneal carcinomatosis model. Therapeutic administration of noni-ppt significantly enhanced the duration of survival of inbred syngeneic LLC tumour bearing mice. It did not exert significant cytotoxic effects in an adapted culture of LLC cells, LLC1, but could activate peritoneal exudate cells (PEC) to impart profound toxicity when co-cultured with the tumour cells. This suggested the possibility that noni-ppt may suppress tumour growth through activation of the host immune system. Concomitant treatment with the immunosuppressive agent, 2-chloroadenosine (C1-Ade) or cyclosporin (cys-A) diminished its activity, thereby substantiating an immunomodulatory mechanism. Noni-ppt was also capable of stimulating the release of several mediators from murine effector cells, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-10, IL-12 p70, interferon-gamma (IFN-gamma) and nitric oxide (NO), but had no effect on IL-2 and suppressed IL-4 release. Improved survival time and curative effects occurred when noni-ppt was combined with sub-optimal doses of the standard chemotherapeutic agents, adriamycin (Adria), cisplatin (CDDP), 5-fluorouracil (5-FU), and vincristine (VCR), suggesting important clinical applications of noni-ppt as a supplemental agent in cancer treatment.

This is a very significant study by a team of researchers from the University of Hawaii led by Annie Hirazumi. Ms. Hirazumi became interested in the study of the Noni fruit because of earlier experiences with its amazing qualities. Her father helped a good friend with the juice of the Noni, and later, Annie administered the pure Noni juice to a pet dog who was dying. The dog recovered miraculously, and Annie set out to find out more about this incredible fruit. The study by Ms. Hirazumi and her colleagues was conducted on live laboratory mice (specifically C57BL/6 mice) specifically identified as very receptive to injected Lewis Lung Carcinoma cells. The mice were injected with active Lewis Lung Carcinoma cells (LLC). Untreated, the mice died from 9-12 days after injection from the tumor growth. A portion of the injected mice were treated with Noni juice in five separate daily treatments. The Noni juice was shown to significantly increase the life span of the treated mice (from 105% 123%) with 9 of the 22 mice surviving for more than 50 days. The experiment was repeated on a different lot of mice with similar results. The Research Team concluded that the Noni juice: seems to act indirectly by enhancing host immune system involving macrophages and/or lymphocytes.

February 9, 1992
Sunday Star-Bulletin & Advertiser

By Jan TenBruggencate
Advertiser Environmental Writer

Much information about native Hawaiian medicinal plants is lost, but several important medicinal herbs are still in regular use in the Islands.

One of them is Noni, which has reputed value in a wide range of ills.

“People are crazy about this plant. They use it for diabetes, high blood pressure, cancer,” and many other illnesses, said Isabella Abbott, G.P. Wilder Professor of Botany at the University of Hawaii.

Abbott said she doesn’t hand out medical advice, but gets plenty of calls from people who are looking for medicinal herbs and can’t locate them. Her interest in ethnobotany, the native uses of plants, has given her the reputation of one who knows where to find useful plants.

And normally, she does know, she said.

The plant about which she gets the most calls, perhaps 10 a week, is Noni, known to science as Morinda citrifolia, she said.

Noni is one of the plants believed to have been brought to Hawaii by early Polynesian immigrants. It is an attractive shrub with large, shiny green leaves, but has one characteristic that limits its value to those who would consider growing it in their yards or gardens.

The fruit stinks.

“It smells like something the dog dragged in,” Abbott said. “It’s a beautiful tree. It is. What I would do is pick off the fruit before they’re ripe.

Medicinally, fortunately, the half-ripe fruit is as good or better than the ripe, or few people would even consider it.

Former University of Hawaii researcher R.M. Heinicke, writing in a 1985 issue of the Bulletin of the National Tropical Botanical Garden, said the fruit contains a natural alkaloid, xeronine, as well as a chemical that is converted to xeronine in the digestive tract. Xeronine may have some beneficial medicinal effects in diseases related to a lack of the chemical, he wrote.

Heinicke, while making no guarantees, lists ailments which in some cases might be eased by the use of Noni juice: high blood pressure, menstrual cramps, arthritis, gastric ulcers, sprains, injuries, mental depression, senility, poor digestion, atherosclerosis, blood vessel problems, drug addiction and others. It may even help relieve pain, Heinicke wrote.

Abbott said she is careful not to promote the use of specific herbs for specific diseases.

“When I talk about ethnobotanical plants, I use all kinds of disclaimers,” she said. But she may also add personal experiences.

Her mother, Abbott said, used the ripe fruit juice on cuts and scrapes, to prevent infection. She assumes that such products as Noni juice or aloe sap simply create a barrier to the entry of germs.

Another plant for which Abbott gets occasional calls is the `uhaloa, a fuzzy-leafed shrub.

The `ulaloa, or hi`aloa, Waltheria indica , is used for sore throats. The outer bark is scraped off the roots, and the inner bark collected. It is mixed with water and used for a gargle, in one use.

Some native plants can be difficult to grow, but can be worth the effort, simply for cultural interest, because they are attractive and because they can be useful.

One upcoming source of plenty of information on the subject is “Polynesian Herbal Medicine,” by ethnobotanist W. Arthur Whistler, to be published later this year by the National Tropical Botanical Garden.