How does ginseng kill cancer cells?
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CM NEWS - Ginseng, a herbal medicine used extensively for centuries in oriental medicine including Chinese, Korean and Japanese as a general tonic to promote longevity can be effective in combating cancer, diabetes, stress, fatigues and oxidants. These effects of ginseng are mainly attributed to a group of compounds called ginsenosides, which recent studies indicate that they might act in a similar way as steroid hormones.
A review of recent studies on ginseng was done by researchers from the UK, Hong Kong and China in a report published on the Chinese Medicine Journal. The report has unveiled the secret behind this longevity-enhancing herb.
What is ginseng? Ginseng is a deciduous perennial plant that belongs to the Araliaceae family. Currently, twelve species have been identified in the genus Panax. Among them, Panax ginseng C. A. Meyer (Araliaceae), cultivated in China, Korea, Japan, Russia, and the US, P. quinquefolium L (American ginseng), grown in southern Canada and the US and P. notoginseng, cultivated in Yunnan and Guangxi provinces in China, represent the three most extensively investigated species.
In modern times, ginseng is not only used as a therapeutic by traditional medical practitioners but is also as health supplements readily available in the commercial market.
“Recently, it has been found that ginsenosides can act as functional ligands to activate different steroid hormone receptors. Through such mechanisms, ginseng can exert its effects on the human body by acting in a similar way as the steroid hormones,” the researchers write.
What are the known effects of ginseng? The pharmacological and therapeutic effects of ginseng have been demonstrated to affect the central nervous system (CNS), cardiovascular system, endocrine secretion, immune function, metabolism, biomodulating action, anti-stress, and anti-aging. Recently, there have been controversies concerning the usefulness of ginseng in cancer therapy.
Most studies claimed that the pharmacological effects of ginseng are attributed to its bioactive constituents such as ginsenosides, saponins, phytosterols, peptides, polysaccharides, fatty acids, polyacetylenes, vitamins and minerals.
So how does ginseng make it? How does it combat cancers?
According to the Chinese Medicine Journal’s report, the anti-tumour effects of ginsenosides include its ability to induce cell death (such as apoptosis and necrosis), and having effects of anti-proliferation, anti-invasion and metastasis, and anti-angiogenesis.
Inducing cell death
Several compounds found in ginsenosides have been shown to induce apoptosis in prostate cancer cells, ovarian cancer cells, neuroblastoma cells and lung adenocarcinoma cells. The induction of tumour cell death by ginsenosides may be one of the mechanisms in the elimination of tumour cells, the writers say.
Anti-proliferation
Ginsenosides also have preventative effects by inhibiting the cell cycle progression. They have been shown to arrest the growth of human tumour cell lines in lung tumour cells, prostate carcinoma cells, leukuemia cells, and hepatoma (liver cancer) cells.
Anti-invasion and anti-metastasis
Cancer metastasis is a complex process involving angiogenesis and cell-cell interactions.
What is cancer metastasis? Metastasis is the spread of cancer from its primary site to other places in the body. Cancer cells can break away from a primary tumour, penetrate into lymphatic and blood vessels, circulate through the bloodstream, and grow in a distant focus (metastasize) in normal tissues elsewhere in the body.
Tumours are classified as either benign or malignant. Malignant tumours can spread by invasion and metastasis whilst benign tumours cannot (and only grow locally). Metastatic tumours are very common in the late stages of cancer. The spread of metastases may occur via the blood or the lymphatics or through both routes. The most common places for the metastases to occur are the adrenals, liver, brain and the bones. There is also a propensity for certain tumours to seed in particular organs.
Scientists recently demonstrated that the invasiveness of some endometrial cancer cells (including those of the uterus) was inhibited by treating them with a certain types of ginsenosides. The inhibitory effect is due to suppression of MMP-2 expression.
What are matrix metalloproteinases (MMPs)? MMPs are capable of degrading all kinds of extracellular matrix proteins. MMPs are also thought to play a major role on cell behaviours such as cell proliferation, migration (adhesion/dispersion), differentiation, angiogenesis, apoptosis and host defense.
The anti-invasive effects of several ginsenosides include the abilities to significantly inhibit in vitro invasion of hepatoma cells, melanoma cells, human lung carcinoma and pancreatic cancer cells. Ginsensodies have also been shown to inhibit lung metastasis, reduce the weight of tumours in lung, breast, gastric and melanoma cancers.
Anti-angiogenesis effects
What is angiogenesis? Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Excessive angiogenesis has been defined as a prominent pathological feature of many diseases such as tumour, rheumatoid arthritis, atherosclerosis, psoriasis and diabetic retinopathy (”diabetic eyes”).
According to the present report, numerous recent studies have demonstrated several ginsenosides exert an anti-angiogenic action in different animal models when administered alone or in combination with other conventional chemicals, such as human breast infiltrating duct carcinoma, ovarian carcinoma cells, melanoma cells and colon carcinoma. These data indicate that one of the mechanisms of anti-metastatic effect of ginsenosides is probably related to suppression of tumour-induced angiogenesis.
A new class of anti-tumour drugs: ginsenosides Rg3 and Rh2?
The researchers say that both gensensides Rg3 and its metabolite form Rh2 have emerged in Mainland China and Taiwan as anti-cancer drugs in the form of capsules (e.g. ‘Rg3 Shenyi Jiaonang’ and ‘GOOD LIFE ginsenoside Rh2 capsule’). Rg3 Shenyi Jiaonang suppresses tumour angiogenesis and prevents adhesion, invasion and metastasis of tumour cells. Rh2 as an adjuvant agent was also tested in the nude mouse model with human ovarian cancer cells transplanted. In the presence of Rh2, cisplatin could significantly inhibit tumour growth in vivo and prolong survival time. Neither Rh2 nor cisplatin alone could inhibit tumour growth. It was shown that chemotherapy supplemented with Rh2 is 60% more effective than chemotherapy alone. It could also mitigate the adverse effects of hair loss, anemia, nausea, vomit and poor appetite following chemotherapy or radiotherapy.
Both Rg3 and Rh2 are extracted from red ginseng which is processed by steaming and drying. During the process, the malonyl group at the C-6 is released and the glycosyl moiety at C-20 is partially detached to generate Rh1, Rh2 and Rg3 through deglycosylation similar to the deglycosylated product, compound K generated from the metabolic transformation of ginsenoside Rb1 by intestinal bacteria. However, whether all of the ginsenosides generated by such post-treatment of white ginseng have similar anti-tumour effects are still not known.
[Chinese Medicine 2007, 2:6 doi:10.1186/1749-8546-2-6]
chinese medicineGinseng, gingko biloba won’t interfere with drug absorption if taken within limit
ginseng" alt="ginseng" class="imageframe imgalignleft" align="left" height="200" hspace="10" vspace="10" width="128" />CM NEWS - Daily use of ginseng or ginkgo biloba supplements at the recommended doses, or the combination of both supplements, are unlikely to alter the pharmacokinetics of most drugs, a study has found.
Recent findings that the widely-used herbal supplement Saint John’s wort could dramatically affect the absorption and metabolism of many prescription and non-prescription drugs raised concerns that other popular herbal supplements might cause similar changes, thus significantly altering drugs’ therapeutic or toxic effects.
What, for example, about ginseng and ginkgo biloba, two of the most widely used herbal supplements? Ginseng and gingkgo biloba are commonlyly used in traditional Chinese medicine.
What are the effects of ginseng? In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides.
Panax qinsenq & Panax quinquefolium are two species of the ginseng plant. The herb grows to a height of about 60 centimeters (around two feet) and belongs to the Araliaceae family.
The plant grows very slowly and requires a cool shady climate. It grows best in China, Korea, and Japan. Ginseng also grows wild in some parts of North America. Indeed, it has been said that the best type is the wild type with roots which are several years old.
The Asian form is the Panax qinsenq, the American variety is the quinquefolium type. Both have many similar properties, but the Chinese version is more useful for a winter tonic because of its warming nature and the American variety is useful for a summer tonic because it has a more yin or cooling nature
There is an entirely different plant called Eleutherococcus senticosus which, although a botanical cousin of ginseng is often sold as “Siberian Ginseng”. It has some similar properties to ginseng.
Korean ginseng is considered by many folks to be the “best”. The most potent ginseng is considered by some to be that which is grown in South Korea, especially in the Kunsan and Kaesong provinces.
Speaking on May 1 at Experimental Biology 2007, University of Kansas Medical Center scientist Dr. Gregory Reed reports a study that found daily use of ginseng or ginkgo biloba supplements at the recommended doses, or the combination of both supplements, are unlikely to alter the pharmacokinetics - by which drugs are absorbed, distributed, metabolized, and eliminated by the body - of the majority of prescription or over-the counter drugs. Dr. Reed’s presentation was part of the scientific program of the American Society for Pharmacology and Experimental Therapeutics.
The research team, led by Dr. Reed and the late Dr. Aryeh Hurwitz, recruited 72 healthy non-smoking adults (31 men and 41 women, ages 20 to 59) who were not taking any prescription drugs or dietary supplements. The participants were given a “cocktail” of five drugs, each drug in the cocktail chosen because it provides a measure of the activity of a key drug metabolism pathway. Taken together, the five drugs in the cocktail provide measurements of the pathways that determine the pharmacokinetics of over 90% of prescription drugs. The scientists then measured the presence of these drugs or their metabolites in each subject’s blood and urine in order to establish a baseline for how each individual absorbed and metabolized the different prescription drugs in the absence of herbal supplements.
The 72 individuals next were randomly assigned to one of four groups. For four weeks, the first group received a ginseng supplement and a placebo for ginkgo biloba; the second received ginkgo biloba and a placebo for ginseng; the third received both ginseng and ginkgo biloba supplements; and the fourth received placebos for both supplements. The prescription drug cocktail was again administered and blood and urine samples taken in order to determine the absorption and metabolism of these drugs in the presence of either or both of the herbal supplements.
What is gingko biloba used for? According to gingko’s fact sheet provided by the National Centre for Complementary and Alternative Medicine:
- Ginkgo seeds have been used in traditional Chinese medicine for thousands of years, and cooked seeds are occasionally eaten. More recently, ginkgo leaf extract has been used to treat a variety of ailments and conditions, including asthma, bronchitis, fatigue, and tinnitus (ringing in the ears).
- Today, people use ginkgo leaf extracts hoping to improve memory; to treat or help prevent Alzheimer’s disease and other types of dementia; to decrease intermittent claudication (leg pain caused by narrowing arteries); and to treat sexual dysfunction, multiple sclerosis, tinnitus, and other health conditions.
The science behind it: Numerous studies of ginkgo have been done for a variety of conditions. Some promising results have been seen for Alzheimer’s disease/dementia, intermittent claudication, and tinnitus among others, but larger, well-designed research studies are needed.
- Some smaller studies for memory enhancement have had promising results, but a trial sponsored by the National Institute on Aging of more than 200 healthy adults over age 60 found that ginkgo taken for 6 weeks did not improve memory.
- NCCAM is conducting a large clinical trial of ginkgo with more than 3,000 volunteers. The aim is to see if the herb prevents the onset of dementia and, specifically, Alzheimer’s disease; slows cognitive decline and functional disability (for example, inability to prepare meals); reduces the incidence of cardiovascular disease; and decreases the rate of premature death.
- Ginkgo is also being studied by NCCAM for asthma, symptoms of multiple sclerosis, vascular function (intermittent claudication), cognitive decline, sexual dysfunction due to antidepressants, and insulin resistance. NCCAM is also looking at potential interactions between ginkgo and prescription drugs.
In this study, the scientists found no significant differences between those who received one, both, or none of the ginseng and ginkgo biloba supplements in how their bodies absorbed or metabolized any of the five prescription drugs.
This suggests, says Dr. Reed, that neither ginseng nor ginkgo biloba will affect the pharmacokinetics of the majority of prescription or over-the counter drugs.
He does note, however, that the team did not investigate any possible effects of the herbal supplements on pharmacodynamic interactions: the way drugs produce desired therapeutic effects or cause adverse side effects. The possibility of these pharmacodynamic, as opposed to pharmacokinetic, interactions remains to be investigated.
Studies in Dr. Reed’s laboratory continue with an examination of the effects of Saint John’s wort on pharmacokinetics of prescription and non prescription drugs and the role of an individual’s genetic makeup in determining the magnitude of the herbal supplement’s effects. This work was supported by the National Center for Complementary and Alternative Medicine of the National Institutes of Health.
Ginseng, flaxseed may fight cancer, but shark cartilage worthless, studies say
ginseng, cancer" title="american ginseng, cancer" class="imageframe imgalignleft" align="left" height="200" hspace="10" vspace="10" width="200" />AP - The first scientific tests of some popular alternative medicine products hint that American ginseng might lessen cancer fatigue and that flaxseed might slow the growth of prostate tumours.
But a big Canadian-U.S. study proved shark cartilage worthless against lung cancer, and doctors said people should not take it.
The research was reported Saturday at an American Society of Clinical Oncology conference.
What is American ginseng? According to information offered by the University of Maryland Medical Centre, the American ginseng plant has leaves that grow in a circle around a straight stem. Yellowish-green umbrella-shaped flowers grow in the center and produce red berries. Wrinkles around the neck of the root tell how old the plant is. This is important because American ginseng is not ready for use until it has grown for four to six years. American ginseng is very expensive and is now being grown on farms in order to protect the wild American ginseng from over-harvesting.
American ginseng products are made from ginseng root and the long, thin offshoots called root hairs. The main chemical ingredients of American ginseng are ginsenosides and polysaccharide glycans (quinquefolans A, B, and C). American ginseng seems to be more relaxing than Asian ginseng, which may have stimulating effects.
American ginseng (dried) is available in water, water-and-alcohol, or alcohol liquid extracts, and in powders, capsules, and tablets. American ginseng is available with other herbs in several combination formulas.
How to take it
Children
- This herb is not recommended for use in children unless under the supervision of a qualified health care provider.
Adult
- Fresh root: 1 - 2 g, once daily for up to 3 months
- Dried root: 1/2 - 2 g, chew and swallow once daily
- Tincture (1:5): 1 - 2 teaspoonfuls, 1 - 3 times daily
- Fluid extract (1:1): 1/4 - 1/2 teaspoonfuls, 1 - 3 times daily
- Standardized extract: 100 - 200 mg, 1 - 3 times daily, standardized to contain 4 - 5% ginsenosides
Reported side effects of taking ginseng include:
- High blood pressure
- Insomnia
- Restlessness
- Anxiety
- Euphoria
- Diarrhea
- Vomiting
- Headache
- Nosebleed
- Breast pain
- Vaginal bleeding
To avoid low blood sugar (hypoglycemia), even in people who do not have diabetes, you should take American ginseng with food.
People with hypertension should not take American ginseng products without specific guidance and instruction from a qualified health care provider. At the same time, people with low blood pressure as well as those with an acute illness or diabetes (because of the risk of a sudden drop in blood sugar), should use caution when taking ginseng.
The safety of taking American ginseng during pregnancy is unknown. Therefore, it is not recommended when pregnant or breastfeeding.
American ginseng should be discontinued at least 7 days prior to surgery. American ginseng can lower blood glucose levels and, therefore, create problems for patients fasting prior to surgery. In addition, American ginseng may act as a blood thinner, thereby increasing the risk of bleeding during or after the procedure.
The ginseng and flaxseed studies are small and preliminary, and specialists warned against making too much of them because the substances tested are not the same as what consumers find on store shelves.
But the results suggest that some herbal remedies eventually may find niches for treating specific cancers, symptoms or side effects. Americans spend millions on these products, which are not approved by the federal Food and Drug Administration, even though no good studies confirm the benefits they tout.
“One of the most common things patients ask me is about these things they have snookered away in their purses” and medicine chests, said Dr. Bruce Cheson, a cancer specialist at Georgetown University Hospital. “They’ll come in with big bags of this stuff.”
Some “natural” remedies such as laetrile or high doses vitamin C proved not helpful and even harmful for cancer patients once they were scientifically studied, he noted. Some keep chemotherapy from working as it should.
“Just because it is a vitamin or a leafy green does not ensure it does not have some harmful effects,” Cheson said.
Herbal products vary widely in their purity and the amount and type of active ingredients. These three federally funded studies used standardized compounds so they could say with some certainty whether they have any effect.
Debra Barton, a research nurse at the Mayo Clinic in Rochester, Minn., tested powdered, four-year-old Wisconsin ginseng root, which is different from Asian ginseng and other varieties commonly sold, to treat the extreme tiredness that most people suffer from cancer or its treatment.
She randomly assigned 282 people with breast, lung, colon and other forms of cancer to take either 750, 1,000 or 2,000 milligrams of ginseng or dummy capsules daily for eight weeks. Neither the participants nor the researchers knew who received what.
One-fourth of those on the two highest doses said their fatigue was moderately or much better, compared with only 10 per cent of those on the low dose or dummy pills.
Results are promising, but it is too soon to recommend that people use ginseng, Barton said. A better idea is exercise, the one treatment already shown to help cancer fatigue, she said.
The flaxseed study was aimed at fighting prostate cancer, not treating a side effect. The edible seed has been used for hundreds of years in cereals and breads and is high in beneficial omega-3 fatty acids and in lignan, a substance that can affect hormone levels and perhaps squelch their cancer-promoting effects.
Four groups of about 40 men who were scheduled to have their prostates removed three weeks later were assigned to get either 30 grams of powdered flaxseed, a low-fat diet, both or neither until their surgery.
After the men’s prostates were removed, researchers found that tumours had been growing 30 to 40 per cent slower in the two groups taking flaxseed, based on how quickly cells were multiplying. Low-fat diets had no effect on this, said Wendy Demark-Wahnefried of Duke University Medical Center, who led the study.
“Our findings are compelling but they’re preliminary,” she cautioned.
But several doctors said flaxseed is nutritious and seems to have little downside other than a sawdust-like consistency, since it must be used ground or powdered because it has an inedible hull or coating.
Scientists plans to study flaxseed on men with prostate cancer that comes back after initial treatment, and Canadian scientists also are testing it for breast cancer, she said.
The shark cartilage study was done because Congress ordered it. Some very small early studies suggested high doses of it might extend survival of people with advanced cases of non-small cell lung cancer, the most common form of the disease.
Dr. Charles Lu of the University of Texas M.D. Anderson Cancer Center in Houston tested Neovastat, a shark cartilage liquid extract that the Canadian company Aeterna-Zentaris was trying to develop as a regular pharmaceutical product.
All 379 people in the study, which was done throughout Canada and the United States, were given standard chemotherapy and radiation. Half also were given shark cartilage twice a day.
After about four years there was no difference in survival, which averaged 15 months for both groups.
On the Net:
Cancer meeting: www.asco.org
Cancer society: www.cancer.org
National Center for Complementary and Alternative Medicine: www.nccam.nih.gov
Ginseng Board of Wisconsin: www.ginsengboard.com
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