Curcumin metabolites; production in liver cells and live rats and activity against cyclooxygenase-2

June 6th, 2009

Curcumin is the chemical part of tumeric which is most active. It prevents cancer in rodents, particularly in the intestines. However curcumin is poorly absorbed when given by mouth. Very little gets into the bloodstream. So these researchers wondered if metabolites of curcumin where really causing the beneficial affects attributed to curcumin. Metabolites are the products made through the metabolism of a chemical in the body. First, they found that isolated liver cells of rats and humans produced two metabolites, hexahydrocurcumin and hexahydrocurcuminol. Rats given curcumin by injection mostly made curcumin glucuronide and curcumin sulfate. They made little hexahydrocurcumin, hexahydrocurcuminol, and hexahydrocurcumin glucuronide. They then studied the effect of these metabolites on an enzyme important in the prevention of cancer, cyclooxygenase-2 (COX-2). They compared how much four metabolites blocked COX-2 activity in cells from the surface the human large intestine. Curcumin complete inhibited COX-2. Tetrahydrocurcumin, hexahydrocurcumin, and curcumin sulfate, only weakly inhibited COX-s. Tetrahydrocurcumin has been shown to be metabolite of curcumin in mice. Hexahydrocurcuminol had no effect. These scientists concluded that the live rats made different curcumin metabolites than did liver cells in a test tube. The metabolites studied inhibit COX-2 had less than curcumin. When curcumin is given by mouth, the cells on the surface of the intestine are directly exposed to curcumin, not metabolites. Therefore they advise studying curcumin as a treatment in colon and rectal cancer.

Characterization of metabolites of the chemopreven…[Cancer Res. 2001]

Rats fed curcumin reduced experimental cataracts

June 6th, 2009

Naphthalene is known to cause cataracts (clouding over of the lens of the eye) in rats and rabbits. Therefore experimental animals are treated with naphthalene in order to model and study cataracts of elderly humans. It is thought that naphthalene causes cataracts through oxidative stress. Curcumin is the most active chemical part of turmeric, a spice used in Indian curry dishes. It is an effective antioxidant. These scientists studied whether low amounts of dietary curcumin slowed the formation of the cataracts usually caused by naphthalene in rats. They looked for apoptotic cells in the cells covering the lens by measuring DNA formation. Both treated rats and control rats were given naphalene to produce experimental cataracts. Only 0.005% (w/w) curcumin was added to the diet of the treated rats. The treated rats had significantly less clouding of their lenses as compared to the control rats. They found, for the first time, that cataracts caused by naphthalene involved apoptosis of the cells covering the lens. Apoptosis is a type of programmed, deliberate cell death in which the cell corpses and fragments are safely disposed. They also found that that curcumin reduced the apoptotic effect of naphthalene.

Tumeric extract by mouth in rabbits reduces the fats that lead to heart disease.

June 6th, 2009

Curcumin is a yellow pigment obtained from roots of Curcuma longa commonly used as a spice and food colouring. These researchers looked at whether curcumin affected the fats that lead to atherosclerosis. They evaluated the effect of an alcohol-water extract obtained from rhizomes of C. longa on these fats in rabbits. To cause atherosclerosis the 18 study rabbits were fed a diet of 95.7% standard chow, 3% lard and 1. 3% cholesterol for 7 weeks. The rabbits were divided into three groups, two treatment groups and a control group. The two treatments were given turmeric extract by mouth, either 1.66 or 3.2 milligrams per kilogram of body weight. The level of several fats and related chemicals and enzymes in the plasma, the liquid part of the blood, was measured. These included low density lipoprotein (LDL) lipid structure, alpha-tocopherol, retinol, LDL thiobarbiturate reactive substances, and LDL lipid hydroperoxides. The concentration of the thiobarbiturate reactive substances is an index of lipid peroxidation and oxidative stress. They also examined the wounds atherosclerotic in the large blood vessel, the aorta. Only the low dose of the extract decreases the peroxidation of LDL. Both treatment groups had lower levels of total plasma cholesterol than the control group. The rabbits treated with the lower dose had lower levels of cholesterol, phospholipids and triglycerides in LDL than the animals treated with the higher dose. They concluded that this extract could be useful in treating diseases of the heart and blood vessels caused by atherosclerosis

Oral administration of a turmeric extract inhibits…[Atherosclerosis. 1999]

Effect of tumeric and curcumin on the chromosomal damage caused by radiation

June 6th, 2009

Both the Indian spice tumeric and curcumin (the most active chemical part of tumeric) are anti-oxidants. Anti-oxidants, chemicals that reduce free radicals, are widely used to try to prevent cancer. These investigators look at whether tumeric and curcumin changed the amount of chromosome damage caused by gamma radiation. Chinese hamster ovary cells were treated with three doses of each drug. The doses were; turmeric (100, 250, and 500 micrograms per milliliter) and curcumin (2.5, 5, and 10 micrograms per milliliter). Then they exposed the cells to radiation (2.5 grays) during different phases of the cell cycle. By itself, turmeric did not increase chromosomal damage. In contrast, curcumin, at 10 micrograms per milliliter, increased the frequency of chromosomal damage. Neither treatment protected the cells from the chromosomal damage caused by radiation. Instead, they found an obvious increase in chromosome abnormalities when two of the doses were combined with radiation. The abnormalities were increased when cells were treated with 500 microg/ml turmeric and radiation during G2/S phase of the cell cycle. The chromosomal abnormalities were also increased with 10 microg/ml curcumin plus radiation during S and G2/S phases. These are the parts of the cycle when DNA is replicated and the cell is prepared for division. The results clearly showed that tumeric and curcumin worsened the damage caused by radiation. They suggest that these treatments can boost the harmful effects of radiation depending on the experimental conditions

Potentiation by turmeric and curcumin of gamma-rad…[Teratog Carcinog Mutagen. 1999]

Kidney disease in diabetic rats was improved by curcumin in the diet

June 6th, 2009

Curcumin is the most active part the yellow Indian spice turmeric (Curcuma longa). These scientists studied its effect in kidney disease in rats. The rats served as a model of the kidney disease that occurs in humans with diabetes. The chemical streptozotocin was used to cause diabetes in Wistar rats. Then the rats were fed Curcumin (0.5%) for 8 weeks. Kidney damage was measured by the amount of proteins passed in the urine. Healthy kidneys do not pass proteins in the urine. They also looked at whether four enzymes that are part of the kidney leaked out into the urine. They measured activities of several key kidney enzymes. These included glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, lactate dehydrogenase, aldose reductase, sorbitol dehydrogenase transaminases, and ATPases. They measured the ratio of polyunsaturated fatty acids to saturated fatty acids. This ratio reflects the health of the kidney membranes. Some of their results showed that curcumin lead to significant reduction in the kidney disease caused by diabetes in these rats. Beneficial conclusions were based on the amount of enzymes and protein in the urine, the activity of kidney ATPases and fatty acid composition of renal membranes. These findings agreed with what they saw when they looked at slices of the kidneys under the microscope. They believe that the improvements they found may have been due to curcumins lowering of blood cholesterol levels.

Amelioration of renal lesions associated with diab…[Mol Cell Biochem. 1998]

Curcumin inhibits the growth of human breast cancer cells

August 16th, 2008

Safe compounds that can stop the growth of tumor cells are possible treatments for cancer. Curcumin is the most active part of the spice turmeric (Curcuma longa). It has activity against cancer in animals. In test tube experiments it suppressed steps of gene expression. These were c-jun/Ap-1 and NF-kappaB activation and type 1 human immunodeficiency virus long-terminal repeat-directed gene expression.  These scientists measured the effects of curcumin on the growth of several breast tumor cell lines. These included hormone-dependent and -independent and multidrug-resistant lines. Cell growth was measures by [3H]thymidine incorporation, Trypan blue exclusion, crystal violet dye uptake and flow cytometry. Curcumin inhibited the growth of all the cell lines tested. The effect of curcumin was greater when it was used for longer times and in greater amounts. Curcumin preferentially arrested cells in the G2/S phase of the cell cycle. These are the parts of the cycle when DNA is replicated and the cell is prepared for division. Curcumin-induced cell death was neither due to apoptosis nor to any significant change in the expression of apoptosis-related genes. Apoptosis is a type of programmed, deliberate cell death in which the cell corpses and fragments are safely disposed. Overall these results suggest that curcumin strongly reduces the growth (proliferation) of breast tumor cells and may be a possible anticancer drug.

Antiproliferative effect of curcumin (diferuloylme…[Anticancer Drugs. 1997]

The formation of cataracts in rats reduced by Curcumin

August 16th, 2008

Cataracts in the elderly are an important health problem worldwide. Cataracts (clouding over of the lens of the eye) are thought to be caused by oxidative stress. Increasing the antioxidant defenses of the lens prevents or delays the formation of cataracts. Anti-oxidants are chemicals that reduce free radicals. Because free radicals cause chain reactions that damage cells, anti-oxidants are thought to help in a number of illnesses. These scientists tested whether curcumin, an antioxidant, present in the spice turmeric, prevented cataract formation in rats. Rats were maintained on a standard diet for 2 weeks. Then they were divided into two groups. One was given a dose of corn oil alone for 14 days. The other group was fed 75 milligrams of curcumin in corn oil per kilogram of weight for 14 days. Their lenses were removed and grown for 72 hours in test tubes. The test tubes contained either no or 100 micromoles of 4-hydroxy-2-nonenal (4-HNE). 4-HNE was used to artificially produce cataracts through a process called lipid peroxidation. As expected, 4-HNE caused clouding of the lenses. The lenses from curcumin fed rats were much more resistant to 4-HNE-induced clouding than were lenses from rats fed oil alone. The lenses from the curcumin fed rats contained significantly more glutathione S-transferase isozyme rGST8-8. By increasing this enzyme curcumin may have reduced the amount of 4-HNE, thereby reducing the cataracts. These studies suggest that curcumin protects against cataracts caused by lipid peroxidation.

Curcumin protects against 4-hydroxy-2-trans-nonena…[Am J Clin Nutr. 1996]

Curcumin blocks the action of HIV-1 (AIDS) enzyme

August 16th, 2008

Curcumin is the most active part of turmeric (Curcuma longa L.), a widely used spice (curry). Curcumin exhibits a variety of drug effects against tumors, inflammation and infections. It is now being tested for treating AIDS in human patients. This study looked at how curcumin affected the enzyme, integrase, of the virus, human immunodeficiency virus type 1 (HIV-1) that causes AIDS. Integrase places HIV-1 DNA into the host chromosomal. This step is needed for the virus to multiply. Curcumin blocked the connection of a piece of viral DNA (40 micro Meters in length) to the human chromosome. When the integrase enzyme was shortened to only the amino acids number 50 to 212 curcumin still stopped the enzyme action. This means that curcumin interacts with the parts of the enzyme called the catalytic core. Two chemical that have shapes and chemistry similar to curcumin, methyl cinnamate and chlorogenic acid, did not block integrase. These results suggest how curcumin works against HIV-1; by inhibiting integrase. HIV-1 integrase is an important target for new drugs against AIDS. So Curcumin could be one the first drugs that block this enzyme, which is a new way of treating AIDS.

Inhibition of human immunodeficiency virus type-1 …[Biochem Pharmacol. 1995]

Dietary curcumin of rats effects chemically induced colon cancer and arachidonic acid metabolism

August 16th, 2008

Past studies show that the metabolism (processing) of arachidonic acid (AA) is important in colon (large intestine) cancer. Several enzymes act on AA to produce important signaling molecules such as prostaglandins. These enzymes include tumor phospholipase A2, phospholipase C gamma 1, lipoxygenase, and cyclooxygenase. These scientists looked at the effect of curcumin in the diet on colon cancer in male F344 rats. They tested whether curcumin changed AA metabolism. They intentionally started colon cancer with azoxymethane. Azoxymethane (AOM) is a substance used in cancer research to cause colon tumors in animals. Rats were fed diets of either no curcumin or 2000 parts per million at five weeks of age. This diet was continued for 54 weeks. At seven week of age animals were injected under the skin with AOM once weekly for two weeks. Curcumin resulted in less frequent colon adenocarcinomas (tumors) and fewer invasive, noninvasive, and total adenocarcinomas. Compared with those not given curcumin, those given curcumin had 57% smaller tumor volume. The rats fed curcumin had reduced activity of four AA metabolism enzymes and reduced AA products in their colons and tumors. The steps through which curcumin prevents these chemically caused colon tumors probably includes the metabolism of arachidonic acid.

Chemoprevention of colon carcinogenesis by dietary…[Cancer Res. 1995]

Natural plant products prevent mammary tumors caused by virus in mice and caused by carcinogen in rats

August 16th, 2008

Four natural plant products; turmeric, beta-carotene, catechin, and betel leaf extract were tested for their activity against tumors in two animal models of cancer. The first model was mammary (breast) tumor expressing C3H (Jax) mice. These mice had mammary tumor virus from birth. Researchers gave virgin female C3H mice turmeric in their diet and beta-carotene, catechin, and betel leaf extract in their drinking water. This resulted in less frequent tumors and smaller tumor size. Giving 5% turmeric in the diet from 2 months of age stopped activity of the enzyme, mammary tumor virus-related reverse transcriptase, and early tumor-like changes in the mammary glands. Also, feeding turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. The second animal model was Wistar rats treated with the cancer-producing chemical 7-12-dimethylbenz(a)anthracene (DMBA). In this model giving the four plant products resulted in less frequent tumors and smaller tumor size. It also delayed the start of mammary tumors.

Chemoprevention of mammary tumor virus-induced an.d..[Breast Cancer Res Treat. 1994]