مشاهدة النسخة كاملة : فوائد الكركم في علاج التهاب القولون التقرحي - Ulcerative Colitis

3rd April 2011, 08:29 PM
Tumor Necrosis factor

TNF is a protein that is released by activated white blood cells, triggering more inflammation, an immune system response and more damage to the mucosa of the colon because of the immune activation. Certain drugs inhibit TNF, hence reducing inflammation and immune system involvement. Infliximab was approved by the FDA for treating ulcerative colitis in March 2005. It is usually given as an intravenous infusions at weeks 0,2 and 6 and then every eight weeks thereafter. It is very useful for inducing and maintaining a remission of ulcerative colitis. Some physicians think that infliximab works better when used in combination with immunmodulators such as 6-mercaptopurine or azathioprine, but there is no definitive evidence based medicine to conclude that infliximab must be used with 6-mp or azathioprine.

Anti-TNF agents in nature

TNF or the effects of TNF are also inhibited by a number of natural compounds, including curcumin (a compound present in turmeric), and catechins (in green tea).

Potential medical uses

Turmeric has been used historically as a component of Indian Ayurvedic medicine since 1900 BC to treat a wide variety of ailments.[8] Research in the latter half of the 20th century has identified curcumin as responsible for most of the biological activity of turmeric.[8] In vitro and animal studies have suggested a wide range of potential therapeutic or preventive effects associated with curcumin. At present, these effects have not been confirmed in humans. However, as of 2008, numerous clinical trials in humans were underway, studying the effect of curcumin on various diseases, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis, and Alzheimer's disease.[9]
In vitro and animal studies have suggested curcumin may have antitumor,[10][11] antioxidant, antiarthritic, antiamyloid, anti-ischemic,[12] and anti-inflammatory properties.[13] Anti-inflammatory properties may be due to inhibition of eicosanoid biosynthesis.[14] In addition it may be effective in treating malaria, prevention of cervical cancer, and may interfere with the replication of the human immunodeficiency virus (HIV).[15] In HIV, it appears to act by interfering with P300/CREB-binding protein (CBP). It is also hepatoprotective.[16] A 2008 study at Michigan State University showed low concentrations of curcumin interfere with Herpes simplex virus-1 (HSV-1) replication.[17] The same study showed curcumin inhibited the recruitment of RNA polymerase II to viral DNA, thus inhibiting its transcription.[17] This effect was shown to be independent of effect on histone acetyltransferase activities of p300/CBP.[17] A previous (1999) study performed at University of Cincinnati indicated curcumin is significantly associated with protection from infection by HSV-2 in animal models of intravaginal infections.[18]
Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation[19] and oxidative DNA damage. Curcuminoids induce glutathione S-transferase and are potent inhibitors of cytochrome P450.
A 2004 UCLA-Veterans Affairs study involving genetically altered mice suggested curcumin might inhibit the accumulation of destructive beta-amyloid in the brains of Alzheimer's disease patients, and might also break up existing plaques associated with the disease.[20]
There is also circumstantial evidence curcumin improves mental functions; a survey of 1010 Asian people who ate yellow curry and were between the ages of 60 and 93 showed those who ate the sauce "once every six months" or more had higher MMSE results than those who did not.[21] From a scientific standpoint, though, this does not show whether the curry caused it, or people who had healthy habits also tended to eat the curry, or some completely different relationship.
Numerous studies have demonstrated curcumin, amongst only a few other things, such as high impact exercise, learning, bright light, and antidepressant usage, has a positive effect on neurogenesis in the hippocampus and concentrations of brain-derived neurotrophic factor (BDNF), reductions in both of which are associated with stress, depression, and anxiety.[22][23][24] Curcumin has also been demonstrated to be a selective monoamine oxidase inhibitor (MAOI) of type MAO-A. These results are in conflict with evidence that curcumin cannot cross the blood-brain barrier.[25]
In 2009, an Iranian group demonstrated the combination effect of curcumin with 24 antibiotics against Staphylococcus aureus. In that study, in the presence of a subinhibitory concentration of curcumin, the antibacterial activities of cefixime, cefotaxime, vancomycin and tetracycline were increased against test strain. The increase in inhibition zone surface area for these antibiotics were 52.6% (cefixime), 24.9% (cephotaxime), 26.5% (vancomycin ) and 24.4% (tetracycline). Also it showed curcumin has an antagonist effect on the antibacterial effect of nalidixic acid against the test strain.[26]
Although many preclinical studies suggest curcumin may be useful for the prevention and treatment of several diseases, the effectiveness of curcumin has not yet been demonstrated in randomized, placebo-controlled, double-blind clinical trials.[27]
From 2010 to 2011, scientists at the Cedars-Sinai Medical Center have created a new molecule from curcumin, a chemical component turmeric, and have found, in laboratory experiments, that the molecule affects mechanisms that protect and help regenerate brain cells after a stroke.[28][29]

Its potential anticancer effects stem from its ability to induce apoptosis in cancer cells without cytotoxic effects on healthy cells. Curcumin can interfere with the activity of the transcription factor NF-κB, which has been linked to a number of inflammatory diseases such as cancer.[30]
A 2009 study suggested curcumin may inhibit mTOR complex I via a novel mechanism.[31]
Another 2009 study on curcumin effects on cancer states it "modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK)".[32]
A 2010 study in malignant brain tumors showed curcumin effectively inhibits tumor cell proliferation, as well as migration and invasion, and these effects may be mediated through interference with the STAT3 signaling pathway.[33]
When 0.2% curcumin is added to diet given to rats or mice previously given a carcinogen, it significantly reduces colon carcinogenesis.[34]
Curcumin has recently been shown to have phyto-estrogenic activity that might contribute to activity against breast cancer.[35] In the murine model of breast cancer metastasis, curcumin inhibits the formation of lung metastases [36] probably through the NF-kappa-B dependent regulation of protumorigenic inflammatory cytokines.[37]


Little curcumin, when eaten, is absorbed:[38] from 2 to 10 grams of curcumin eaten alone resulted in undetectable to very low serum levels.[39] Curcumin is unstable in the gut,[40] and the traces that pass through the GI tract rapidly degrade or are conjugated through glucuronidation.
There have been several commercial products developed to provide an alternate route to curcumin. For example, curcumin supplements with piperine are readily available. But curcumin in a non-solubilized pill form can limit bioavailability. Other products, such as Nutmeric,[41] provide curcumin in an oil-solubilized form similar to Indian curry preparations.
Co-supplementation with 20 mg of piperine (extracted from black pepper) significantly increased the absorption of curcumin by 2000% in a study funded by a prominent manufacturer of piperine.[39] However, the increase in absorption only occurred during the first hour, after which the difference between the piperine curcumin and the regular curcumin was almost the same as far as absorption. Due to its effects on drug metabolism, piperine should be taken cautiously (if at all) by individuals taking other medications.
Another curcumin proprietary formulation, (BCM-95®) mixed with turmeric oils, was shown in human cross-over bioavailability comparison tests to have 8 times the bioavailability and greater blood retention time than standard 95% and up to 5 times more than curcumin combined with lecithin and piperine.[42]
This same formula was also shown to remain above 200 ng/g for 12 hours in a human clinical study. Plain curcumin remained above 200 ng/g for less than 2 hours. Two hours after ingestion, BCM-95 levels where 10-fold over that of plain curcumin.[43]
While further research will determine more definite outcomes, in a six-month placebo-controlled, double-blind clinical trial, individuals in the BCM-95 groups (receiving either 1 g or 4 g) saw reduced oxidative stress and improved antioxidant status. There were more adverse effects in the placebo group than in either 1 g or 4 g BCM-95 group. There was a noted increase in serum amyloid beta in both 1 g and 4 g groups, but not placebo. The authors noted this “possibly reflected an ability of curcumin to disaggregate amyloid beta deposits in the brain, releasing the amyloid beta for circulation and disposal.”[44]
Some benefits of curcumin, such as the potential protection from colon cancer, may not require systemic absorption. Alternatively, dissolving curcumin in hot water or in warm oils prior to ingestion may possibly increase bioavailability; however, no published studies to date have documented this. Cooking with curcumin and oil may increase absorption, but peer-reviewed scientific literature has not documented this, while the literature has documented concerns regarding the heat stability of curcumin and its degradation in the gut.[citation needed]
In 2007, a polymeric nanoparticle-encapsulated formulation of curcumin ("nanocurcumin"[45]) has been synthesized which has the potential to bypass many of the shortcomings associated with free curcumin, such as poor solubility and poor systemic bioavailability. Nanocurcumin particles have a size of less than 100 nanometers on average, and demonstrate comparable to superior efficacy compared to free curcumin in human cancer cell line models.[45] However, actual in vivo absorption has not been demonstrated with this nanoparticle.
In July 2008, researchers from the aforementioned team in UCLA's Department of Neurology announced results on a form of "lipidated curcumin" that was noted to achieve more than 5 micromolar in the brain in vivo, 50 times that found in clinical studies.[46] Another method to increase the bioavailability of curcumin was filed in a patent in 2006[47] and involves a simple procedure creating a complex with soy phospholipids; the plasma concentration of free curcumin and curcumin glucuronide using this method increased by 5-fold and by 20-fold, free curcumin reaching 33.4 nanomolar in comparison to 6.5 and curcumin glucuronide reaching 4,420 in comparison to 225 nanomolar obtained with an equal molar quantity of unformulated curcumin administered as control.[48]
In the year of 2010, a food-grade polymer micellar encapsulation system was shown to increase curcumin's water solubility and in vitro anti-cancer activity. It was found that hydrophobically modified starch, usually used to encapsulate flavors, was able to form polymer micelles. Using a simple high-speed homogenization method, it can load curcumin into its hydrophobic core, and thus solubilize curcumin. Cell culture experiments revealed an enhanced anti-cancer activity on HepG2 cell line. However, more in vivo studies are needed to further prove its efficacy in the aspect of bioavailability.

Potential risks and side effects

Kawanishi et al. (2005) remarked that curcumin, like many antioxidants, can be a "double-edged sword" where, in the test tube, anticancer and antioxidant effects may be seen in addition to pro-oxidant effects.[50] Carcinogenic effects are inferred from interference with the p53 tumor suppressor pathway, an important factor in human colon cancer.[51] Carcinogenic and LD50 tests in mice and rats, however, have failed to establish a relationship between tumorogenesis and administration of curcumin in turmeric oleoresin at >98% concentrations.[52] Other in vitro and in vivo studies suggest that curcumin may cause carcinogenic effects under specific conditions.[53][54]
Clinical studies in humans with high doses (2–12 grams) of curcumin have shown few side effects, with some subjects reporting mild nausea or diarrhea.[55] More recently, curcumin was found to alter iron metabolism by chelating iron and suppressing the protein hepcidin, potentially causing iron deficiency in susceptible patients.[56] Further studies seem to be necessary to establish the benefit/risk profile of curcumin.[57]
There is no or little evidence to suggest curcumin is either safe or unsafe for pregnant women. However, there is still some concern medicinal use of products containing curcumin could stimulate the uterus, which may lead to a miscarriage, although there is not much evidence to support this claim. According to experiments done on rats and guinea pigs, there is no obvious effect (neither positive, nor negative) on the pregnancy rate or number of live or dead embryos.[58] Curcumin has embryotoxic and teratogenic effects on zebrafishes (Danio rerio) embryos.[59]