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Curcumin, An Atoxic Antioxidant and Natural NF[Kappa]B, Cyclooxygenase-2, Lipooxygenase, and Inducible Nitric Oxide Synthase Inhibitor: A Shield Against Acute and Chronic Diseases

Posted on: Tuesday, 17 January 2006, 03:02 CST

By Bengmark, Stig

ABSTRACT. Background: The world suffers a tsunami of chronic diseases, and a typhoon of acute illnesses, many of which are associated with the inappropriate or exaggerated activation of genes involved in inflammation. Finding therapeutic agents which can modulate the inflammatory reaction is the highest priority in medical research today. Drugs developed by the pharmaceutical industry have thus far been associated with toxicity and side effects, which is why natural substances are of increasing interest. Methods: A literature search (PubMed) showed almost 1500 papers dealing with curcumin, most from recent years. All available abstracts were read. Approximately 300 full papers were reviewed. Results: Curcumin, a component of turmeric, has been shown to be non- toxic, to have antioxidant activity, and to inhibit such mediators of inflammation as NFκB, cyclooxygenase-2 (COX-2), lipooxygenase (LOX), and inducible nitric oxide synthase (iNOS). Significant preventive and/or curative effects have been observed in experimental animal models of a number of diseases, including arteriosclerosis, cancer, diabetes, respiratory, hepatic, pancreatic, intestinal and gastric diseases, neurodegenerative and eye diseases. Conclusions: Turmeric, an approved food additive, or its component curcumin, has shown surprisingly beneficial effects in experimental studies of acute and chronic diseases characterized by an exaggerated inflammatory reaction. There is ample evidence to support its clinical use, both as a prevention and a treatment. Several natural substances have greater antioxidant effects than conventional vitamins, including various polyphenols, flavonoids and curcumenoids. Natural substances are worth further exploration both experimentally and clinically. (Journal of Parenteral and Enteral Nutrition 30:45-51, 2006)

Chronic diseases (ChD) constitute a fast-increasing burden to society. The World Health Organization estimates that 46% of global disease burden and 59% of global mortality is due to ChD; 35 million individuals die each year from ChD, and the numbers are increasing steadily.

The painful increase in costs for health care in recent decades is expected to continue and to accelerate. This is not only because the numbers of patients with ChD is increasing but also because treatments are becoming more sophisticated and thereby more expensive. For example, the costs of diabetes doubled during the past 5 years. If these trends continue, most healthcare systems, socialized or private, will be in great trouble, and dramatic and painful cuts in privileges will be unavoidable. In 2002, $1.6 trillion was spent in the US on health care, about $5440 for every person, an expense expected to double by 2011.1 In order to prevent a total collapse of the system, preventive measures will be increasingly necessary.

The cost of medication is a large and growing part of health expenditure. This is one of many reasons why inexpensive alternatives to standard pharmaceuticals for prevention and treatment of disease, methods which have been successfully practiced for centuries in countries such as India and China, are increasingly attractive. Agents with the documented ability to boost resistance and decrease vulnerability to disease, often referred to as chemopreventive agents, will have an important role to play. These substances are not only inexpensive, they are also easily available and have limited or no toxicity. Among these chemopreventive agents are a series of phenolic and other compounds believed to reduce aging and prevent degenerative malfunctions of organs: isothiocyanates in cruciferous vegetables, epigallocatechin-3- gallate (EGCG) in green tea, caffeic acid in coffee, capsaicin in hot chili peppers, chalcones in apples, euginol in cloves, gallic acid in rhubarb, hisperitin in citrus fruits, naringenin in citrus fruits, kaempferol in white cabbage, myricetin in berries, quercetin in apples and onions, resveratrol and other procyanidin dimers in red wine, and various curcumenoids found in turmeric (TU) curry.

Curcumin (CU): A Promising Tool

Interest in polyphenols, and especially in CU as a chemoproctive agent, has dramatically increased in recent years. CU, the most explored of the curcumenoids, has received increasing interest in recent years. The majority of studies reported thus far are experimental and few clinical studies have been published. This review is intended to provide a comprehensive description of the experimental and clinical effects of treatment with CU.

The nuclear factor NFκB plays a critical role in several signal transduction pathways involved in chronic inflammatory diseases2 such as asthma and arthritis and various cancers.3 Activation of NFκB is linked with apoptotic cell death, either promoting or inhibiting apoptosis, depending on cell type and condition. The expression of several genes such as cyclooxygenase-2 (COX-2), matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF), interleukin-8 (IL-8), eotaxin, cell surface adhesion molecules, and antiapoptotic proteins are regulated by NFκB.4 The cyclooxygenases are responsible for prostaglandin synthesis. Although COX-1 is constitutive and required for normal "housekeeping" functions, COX-2 is inducible and barely detectable under normal physiologic conditions. It is rapidly but transiently induced as an early response to proinflammatory mediators and mitogenic stimuli, including cytokines, endotoxins, growth factors, oncogenes, and phorbol esters. COX-1 is responsible for protection of mucosal surfaces, maintenance of renal function, and platelet activity and stability. COX-2 synthesizes series-2 prostaglandins (PGE2, PGF2-α), which contribute to inflammation, swelling, and pain. Among the functions of PGE2 are promotion of IL-10, an immunosuppressive cytokine, and suppression of IL-12.5 Another enzyme that plays a pivotal role in mediating inflammation is iNOS. iNOS is activated by NFκB and acts in synergy with COX-2 to promote the inflammatory reaction.

TU: An Approved Food Additive

CU, 1,7-bis(4-hydroxy-3-methoxyphenol)-1,6heptadiene-3,5-dione), is a polyphenol found in the dietary spice TU, derived from dried rhizozomes of the perennial herb Curcuma longa Linn, a member of the ginger family. It is a lipophilic molecule with phenolic groups and conjugated double bonds. Its molecule resembles ubiquinols and other phenols known to possess strong antioxidant activities. Its bioavailability from oral administration is low but can be improved by dissolution in ambivalent solvents (glycerol, ethanol, DMSO).6 Its bioavailability has been reported to be increased by coingestion of peperine (a component of pepper), a finding that has been demonstrated in both experimental animals and humans.7 TU is mainly known for its ability to preserve food and is approved as a food additive in most Western countries. It is produced in several Asian and South American countries. In India alone, about 500,000 metric tons are produced each year, of which about half is exported. It has been used for generations in traditional medicine for the treatment of inflammatory conditions such as arthritis, colitis, and hepatitis. Several studies have demonstrated that CU is nontoxic, even in very high doses.8,9 Treatment of humans during 3 months with 8000 mg CU per day showed no side effects.9 It is estimated that most adult Indians consume 80-200 mg CU per day.10 A common therapeutic dose is 400-600 mg CU 3 times daily, corresponding to up to 60 g fresh TU root or about 15 g TU powder. The content of CU in TU is usually 4%-5%.

CU Controls Stress-Induced Overinflammation

CU inhibits COX-2 and iNOS inhibits arachidonic acid metabolism, modulates cellular signal pathways, and inhibits certain hormonal, growth factor, and oncogene activities.11 It is also a potent inducer of cytoprotective heat shock proteins (HSP).12,13 CU inhibits lipooxygenases (LOX) and leukotreines such as LBT4 and 5HETE,14 especially when bound to phosphatidylcholine micelles.15 It is reported to inhibit cytochrome P450 isoenzymes and thereby activation of carcinogens.16 CU can intercept and neutralize potent prooxidants and carcinogens, both ROS (reactive oxygen species, Superoxide, peroxyl, hydroxyl radicals) and NOS (nitric oxide, NO; peroxynitrite).17 It is also a potent inhibitor of TGF-β and fibrogenesis,18 which may explain its positive effects in diseases such as kidney fibrosis, lung fibrosis, liver cirrhosis and Crohn's disease, and in prevention of the formation of tissue adhesions.19 It has been suggested that CU is effective in Thl-mediated immune diseases.20

Many medicinal herbs and pharmaceutical drugs are therapeutic at one dose and toxic at another. Interactions between herbs and drugs, even if structurally unrelated, may increase or decrease the pharmacologic and toxicological effects of either component.21,22 It is suggested that CU may increase the bioavailability of vitamins such as vitamin E and decrease cholesterol. In experimental studies, CU significantly raises the concentration of α-tocopherol in lung tissues and decreases plasma cholesterol.23 Polyphenols, iso\thiocyanates such as CU and flavonoids such as resveratrol, are all made accessible for absorption into the intestinal epithelial cells and the rest of the body by digestion/fermentation in the intestine by microbial flora.24 CU binds to albumin, by hydrophobic interactions, and may thereby be transported to appropriate target cells, where it elicits its pharmacologie effects.25 It is also reported to form intracellular conjugates with glutathione.26

CU to Prevent and Treat Diseases

Atherosclerosis. Hyperhomocysteinemia, an expression of increased prooxidant activity in the body, is generally regarded as a cardiovascular risk factor, equivalent to hypercholesterolemia.27 High intake of antioxidants and vitamins, particularly B-vitamin- rich foods and Mate, is known to be associated with reduced total plasma homocysteine (tHcy) and lower incidence of cardiovascular disease.28,29 A strong inverse association has been reported between low levels of plasma concentrations of vitamin E, high levels of plasma cholesterol, and presence of carotid arteriosclerosis.30 CU may prevent lipid peroxidation, stabilize cellular membranes, inhibit proliferation of vascular smooth muscle cells, and inhibit platelet aggregation, all important ingredients in the pathogenesis of arteriosclerosis. When the ability of CU, quercetin, capsaicin and a defined antioxidant, butylated hydroxyl anisole (BHA) to inhibit the initiation and propagation phases of low density lipoprotein (LDL) oxidation were compared, CU was found to be the most effective and quercetin the least.31 Cellular membranes, such as those of erythrocytes, which contain excess cholesterol content show reduced fluidity and become fragile. CU, capsaicin, and garlic (allecin), fed to rats receiving a cholesterol-enriched diet, prevented both the increase in membrane cholesterol and the increased erythrocyte fragility.32 Dietary curcumenoids have been reported to increase hepatic acyl-CoA and prevent high-fat dietinduced accumulation in the liver and adipose tissues in rats.33 CU was reported to prevent early atherosclerotic lesions in the thoracic and abdominal aorta, in parallel with significant increases in plasma concentrations of coenzyme Q, retinol, and α- tocopherol and reductions in LDL-conjugated dienes and TBARS (thiobarbituric acid-reactive substances), which were observed in rabbits fed an atherogenic diet for 30 days.34

Diabetes. Insulin resistance syndrome is associated with elevated tHcy and increased lipid oxidation.35 TU (1 g/kg body weight) or CU (0.08 g/kg body weight) was supplied daily for 3 weeks to rats with alloxan-induced diabetes (AID). Then, healthy controls (CO) were compared with diabetic animals (AID) and with animals treated with CU.36 Significant improvements were observed in blood glucose (mg/ dL CO 88.3, AID 204.4, TU 142.7, CU 140.1), hemoglobin (gm/dL CO 14.7, AID 10.8, TU 13.6, CU 13.1), and glycosylated hemoglobin (gm/ dL CO 2.8, AID 11.2, TU 9.0, CU 7.8). Significant differences were also observed in TBARS in liver tissue (nmol/g tissue CO 43.0, AID 54.0, TU 34.0, CU 29.0), TEARS in plasma (nmol/mL CO 3.8, AID 7.3, TU 5.3, CU 4.6), glutathione in liver (g/mg CO 23.4, AID 11.2, TU 16.6, CU 20.9), and glutathione in plasma (mg/dL CO 22.4, AID 14.2, TU 18.4, CU 20.1). Activity of sorbitol dehydrogenase (SDH), which catalyzes the conversion of sorbitol to fructose, was significantly lowered by treatment with both TU and CU.

Respiratory diseases. As mentioned above, CU is a potent inhibitor of TGF-β and fibrogenesis18 and may have positive effects in fibrotic diseases in kidneys, liver, intestine (Crohn's disease), body cavities (prevention of fibrous adhesions),19 and lung fibrosis, including cystic fibrosis. The latter is of special interest as it has been linked to glutathione deficiency. The effect of CU upon amiodarone-induced lung fibrosis was recently studied in rats.37 Significant inhibition of LDH activity, infiltration of neutrophils, eosinophils and macrophages in lung tissue, LPS- stimulated TNF-α release, phorbol myristate acetate (PMA)- stimulated superoxide generation, myeloperoxidase (MPO) activity, TGF-β1 activity, lung hydroxyproline content and expression of type I collagen and c-Jun protein were observed when CU was supplemented (200 mg/kg body weight) in parallel with intratracheal instillation of 6.25 mg/kg body weight of amiodarone. CU exhibits structural similarities to isoflavonoid compounds that are thought to bind directly to the cystic fibrosis transmembrane conductance regulator (CFTR) protein and alter its channel properties.38 Egan et al,39 who had previously observed that CU inhibits a calcium pump in endoplasmic reticulum, thought that reducing calcium levels might liberate the mutant CFTR and increase its odds of reaching the cell surface (see also Zeitlin40). The ΔF508 mutation, the most common cause of cystic fibrosis, will induce a misprocess in the endoplasmic reticulum of a mutant CFTR gene. A dramatic increase in survival rate and in normal cAMPmediated chloride transport across nasal and gastrointestinal epithelia was observed in gene-targeted mice homozygous for the AF508 when supplemented CU.38 No human studies are yet reported, and it is too early to know if this treatment will be able to halt or reverse the decline in lung function also found in patients with cystic fibrosis. An eventual antiasthmatic effect of CU was recently tested in guinea-pigs sensitized with ovalbumin. Significant reductions were observed both in airway constriction and in airway hyperreactivity to histamine.41

Liver diseases. Ethanol-induced steatosis is known to be further aggravated by supply of PUFA-rich vegetable oils that have been thermally oxidized. Rats fed by gavage for 45 days with a diet containing 20% ethanol and 15% sunflower oil, heated to 180C for 30 minutes (AO), showed extensive histopathological changes, with focal and feathery degeneration, micronecroses and extensive steatosis in the liver, and extensive congestion and fatty infiltration in the kidneys. These changes were largely prevented by administration of CU, particularly photo-irradiated CU (PCU, CU kept in bright sunshine for 5 hours).42 Both products were supplied in a dose of 80 mg/kg/d. Both products significantly inhibited elevations in alkaline phosphatases (ALP): CO 85.88, high fat diet (AO) 239.56, CU 177.41 and PCU 149.15; and in γ-glutamyl transferase (GGT): CO 0.60, AO 2.51, CU 1.43, PCU 1.15. Similar beneficial effects were observed on histology in various tissues and in hepatic content of cholesterol, triglycrides, free fatty acids, and phospholipids. Rats in another study were fed for 4 weeks with fish oil and ethanol (FE), which resulted in hepatic lesions consisting in fatty liver, necrosis, and inflammation. CU in a daily dose of 75 mg/kg/d to these rats prevented the histologic lesions.43 CU suppressed NFκB-dependent genes, blocked endotoxin-mediated activation of NFκB, and suppressed the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. Similar effects were also observed in carbon tetrachloride-induced injuries. Pretreatment for 4 days (100 mg/kg/d body weight) with CU before intraperitoneal injection Of CCl^sub 4^ prevented significantly subsequent increases in TEARS: CO 274, CCl^sub 4^ 556, CU 374, alanine aminotransferase (ALT): CO 46, CCL^sub 4^ 182, CU 97 and aspartate aminotransferase (AST): CO 97, CCl^sub 4^ 330, CU 211 and in hydroxyproline (y-g/g liver tissue): CO 281, CCl^sub 4^ 777, CU 373.44

Pancreatic diseases. The effect of CU was studied in 2 different models of pancreatitis: cerulein-induced and ethanol CCK-induced.45 CU was administered IV in parallel with induction of pancreatitis. A total of 200 mg/kg/d weight was administered during the treatment period of 6 hours. CU treatment significantly reduced histologie injuries of the pancreatic tissue (acinar cell vacuolization and neutrophil infiltration), intrapancreatic activation of trypsin, hyperamylasemia, hyperlipasemia, pancreatic activation of NFκB, IκB degradation, activation of activator protein (AP)-I, and inflammatory molecules such as IL-6, TNF-α, chemokine KC, iNOS, and acidic ribosomal phosphoprotein (ARP). CU in both models also stimulated pancreatic activation of caspase-3, a mediator of apoptosis.

Gastric diseases. Both a methanol extract of TU and pure CU were tested in vitro against 19 different HeIicobacter pylori strains, including 5 cagA+ strains (cag A is the strain-specific H pylori gene linked to premalignant and malignant lesions). Both treatments were equally effective and both significantly reduced growth of all strains tested.46 Subsequent studies demonstrate that CU inhibits the infection and inflammation of gastric mucosal cells by inhibiting activation of NFκB, degradation of I&945;, NFκB binding to DNA, and activity of IκB kinases α and β. No CU-induced effects were observed on mitogen- activated protein kinases (MAPK), extracellular signal regulating kinases 1 and 2 (ERK1/2), and p38. However, the H py/ori-induced mitogenic response was blocked by CU.47 Significant antifungal properties against various fungal organisms, especially phytopathogenic, by CU have also been reported.48

Intestinal diseases. Inflammatory bowel disease is associated with overproduction of NO, induced by increased expression of the iNOS. Various attempts to reduce this expression have been made.49 Pretreatment during 10 days with CU at 50 mg/kg/d before induction of trinitrobenzene sulfonic acid (TNBS) colitis resulted in a significant reduction of histologic tissue injury, neutrophil infiltration (measured as decreased myeloperoxidase activity), and lipid peroxidation (measured as decreased malondialdehyde activity) in the inflamed colon and in decreased serin protease activity.50 A significant reduction in NF \14;B activation, reduced levels of NO, and marked suppression of ThI functions (IFNγ and IL-12p40 mRNA) were also observed. In another similar study, CU was added to the diet 5 days before induction of TNBS colitis, resulting in a significant reduction in myeloperoxidase and attenuation of the TNBS- induced message for IL-1β on semiquantitative RT-PCR.51 Western blotting revealed a significant attenuation of the activation of p38 MAPK. CU was supplied in combination with caffeic acid phenethyl ester (CAPE) to animals treated with cytostatic drugs (arabinose cytosine, Ara-C, and methotrexate, MTX).51 The treatment inhibited the NFκB-induced mucosal barrier injury and increased the in vitro susceptibility of the nontransformed small intestinal rat epithelial cell, IEC-6, to the cytostatic agents.

Cancer. Cancer is a group of > 100 different diseases, which manifest themselves in uncontrolled cellular reproduction, tissue invasion1, and distant metastases.52 Behind the development of these diseases is often exposure to carcinogens, which produce genetic damage and irreversible mutations if not repaired. During the last 50 years, attempts have been made to find or produce substances that could prevent these processes, so-called chemopreventive agents. Cancers are generally less frequent in the developing world, associated both with less exposure to environmental carcinogens and a richer supply of natural chemopreventive agents. The incidence per 100,000 population in the USA is considerably higher than in India for the following diseases: prostatic cancer (23 times), melanoma of the skin (male 14 times, female 9 times), colorectal cancer (male 11 times, female 10 times), endometrial cancer (9 times), lung cancer (male 7 times, female 17 times), bladder cancer (male 7 times, female 8 times), breast cancer (5 times), and renal cancer (male 9 times, female 12 times).53 These differences are even greater when compared with China for some diseases, such as breast cancer and prostatic cancer. Consumption of saturated fat and sugary foods is much less common in the Asian countries, but equally important, consumption of plants with high content of chemopreventive substances is significantly higher in these countries. As an example, the consumption of CU has for centuries been about 100 mg/ d in these Asian countries.54 CU induces in vitro apoptosis of various tumor cell lines: breast cancer cells,54,55 lung cancer cells,56 human melanoma cells,57 human myeloma cells,58 human leukemia cell lines,59 human neuroblastoma cells,60 oral cancer cells,61 and prostatic cancer cells.62-65 CU also inhibits intrahepatic metastases in experimental models.66

Few in vivo experimental studies and no clinical controlled trials are concluded thus far. However, a recent phase I study reported histologic improvement of precancerous lesions in 1 of 2 patients with recently resected bladder cancer, 2 of 7 patients of oral leukoplakia, 1 of 6 patients of intestinal metaplasia of the stomach, and 2 of 6 patients with Bowen's disease.67 This was a small study, but its main purpose was to document that CU is not toxic to humans up to 8000 mg/d when taken by mouth for 3 months. Improvement of lesions was an incidental but highly suggestive finding.

Neurodegenemtive diseases. A growing body of evidence implicates free radical toxicity, radical induced mutations, oxidative enzyme impairment and mitochondrial dysfunction in neurodegenerative diseases (NDD). Significant oxidative damage is observed all NDDs, which in the case of Alzheimer's disease (AD) leads to extracellular deposition of β-amyloid (Aβ) as senile plaques. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen have proven effective in prevention of the progress of AD in animal models.68 Gastrointestinal and occasional liver and kidney toxicity induced by inhibition of COX-1 precludes widespread chronic use of such drugs.69 Use of antioxidants such as vitamin E (α- tocopherol) has proven unsuccessful even when high doses were used.70 Vitamin E, α-tocopherol, is in contrast to γ- tocopherol a poor scavenger of NO-based free radicals. CU is a several times more potent scavenger than vitamin E71and is also a specific scavenger of NO-based radicals.72 When used in a transgenic mouse model of AD, a modest dose of CU (24 mg/kg body weight), but not a much higher dose (750 mg/kg), significantly reduced oxidative damage and amyloid deposition.73 Similar observations, reductions in both Aβ deposits and in memory deficits, have also been noted in Sprague-Dawley rats.74 The age-adjusted prevalence of both AD75 and Parkinson's disease (PD) in India,76 with its significantly higher intake of TU, is much lower than in Western countries. However, the preventive effects of consumption of TU can also be achieved with other polyphenol-rich fruits and vegetables if consumed in enough quantities. Blueberries, strawberries, and spinach in doses of 18.6, 14.8, and 9.1 g of dried extract/kg body weight were effective in reversing age-related deficits in both neuronal and behavioral parameters.77 A study from 1999 is of special interest. Rats on chronic ethanol were randomized to 80 mg/ kg body weight of CU.78 Nonintoxicated normal rats (ND were compared with rats given ethanol without CU (ND and with CU-treated rats (CU). The degree of histopathological changes, the levels of TBARS (NI 1.29, CO 2.98, CU 2.41), cholesterol (NI 1531.9, CO 2031.1, CU 1658.2), phospholipids (NI 1845.5, CO 2795.1, CU 2011. 5), and free fatty acids (NI 26.7, CO 53.1, CU 39.9) in brain tissue were all significantly improved after CU treatment.

Ocular opacities. Cataract, an opacity of the eye lens, is the leading cause of blindness worldwide and is responsible for the blindness of almost 20 million people in the world.79 Nutrition deficiencies, especially lack of consumption of antioxidants, diabetes, excessive sunlight, smoking, and other environmental factors are known to increase the risk of cataracts.80 The age- adjusted prevalence of cataract in India is, however, 3 times that of the United States.81 Despite that, 3 different experimental studies have reported significant preventive effects of CU against cataracts induced by naphthalene,82 galactose,83 and selenium.84

Tobacco/cigarette smoke (CS)-induced injuries. CS is suggested to cause 20% of all deaths and about 30% of all deaths from cancer. CS contains thousands of compounds of which about 100 are known carcinogens, cocarcinogens, mutagens, or tumor promoters. Each puff of smoke contains >10 trillion free radicals. Antioxidant levels in blood are significantly reduced in smokers. Activation of NFB has been implicated in chemical carcinogenesis and tumorigenesis through activation of several genes such as COX-2, iNOS, MMP-9, IL-8, cell surface adhesion molecules, antiapoptotic proteins, and others. A recent study reported that CU suppresses activation of NFκB, which correlates with down-regulation of COX-2, MMP-9, and cyclin D1 in human lung epithelial cells.85

Other Studies

Increasing evidence suggests that saturated fat in the diet increases and plant fiber intake reduces inflammatory reaction in the body.86 A high fat/low fiber diet is apparently associated with many chronic diseases.87 Fruit and vegetable intake is associated with a reduction in the incidence of chronic diseases.88 Focus is increasingly turning from fiber per se to active ingredients in plants, such as CU in TU. The only active ingredients to be reasonably explored with regard to their potential to enhance human health are those in the soya bean and more recently in TU. However, other compounds, including resveratrol in red wine and peanuts and quercetin in apples and onions and others, might prove equally powerful. This assumption is supported by a recent study using PCSPES, a partially extracted composition of 8 herbs, all different from those mentioned above.89 PC-SPES inhibited LPS induced production of murine macrophages and decreased their production of proinflammatory cytokines, including TNFa, IL-1β, and IL-6 and the inducible enzymes COX-2 and iNOS. Furthermore, PC-SPEC rescued C57BL/6 mice from death by LPS induced septic shock in conjunction with decreased levels of TNFa and IL-1β.89 PC-SPES has also been shown to inhibit growth of and induce apoptosis of various human cancer cells.90-92

One of the negative characteristics of CU is its low absorption and low availability in certain tissues such as the liver.93 However, the efficacy of CU can most likely be improved both by modification of the CU molecule,42 and production of new synthetic analogs.94

CONCLUSIONS

The use of medicinal plants and their active components is becoming an increasingly attractive approach for the treatment of various inflammatory disorders among patients unresponsive or unwilling to take standard medicines. Food derivates have the advantage of being relatively nontoxic. This is certainly so for TU and CU. If one chooses to supply CU together with its fiber (eg, as TU), the effects from the intake of fiber and from the active chemopreventive agent, CU and other curcumenoids, may be potentiated.

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Stig Bengmark, MD, PhD, FRACS (bon), FRCPS (bon)

From the Institute of Hepatology, University College, London Medical School, London, United Kingdom

Received for publication November 12, 2004.

Accepted for publication August 4, 2005.

Correspondence: Stig Bengmark, MD, PhD, FRACS (hon), FRCPS (hon), 185 Barrier Point Road, Royal Docks, London, E16 2SE, United Kingdom. Electronic mail may be sent to s.bengmark@ucl.ac.uk.

Copyright American Society for Parenteral and Enteral Nutrition Jan/ Feb 2006

Source: JPEN, Journal of Parenteral and Enteral Nutrition

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