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Curcumin, an antioxidant and anti-inflammatory phytochemical agent, Research for Immune Support and Anti Cancer Properties
Curcumin is an antioxidant and anti-inflammatory phytochemical agent which has been shown to have anticancer properties. Curcumin is the yellow pigment of the spice Tumeric. Curcumin also can be a digestive aid and when used as a paste can have anti fungal properties. I am including research articles on Curcumin so you can see its many uses.

Biochem Pharmacol. 2003 Oct 15;66(8):1475-83. : Induction of apoptosis by curcumin: mediation by glutathione S-transferase P1-1 inhibition.
Duvoix A, Morceau F, Delhalle S, Schmitz M, Schnekenburger M, Galteau MM, Dicato M, Diederich M.
Laboratoire de Recherche sur le Cancer et les Maladies du Sang, Centre Universitaire de Luxembourg, 162A Avenue de la Faiencerie, L-1511 Luxembourg, Luxembourg.

Expression of glutathione S-transferase P1-1 (GSTP1-1) is correlated to carcinogenesis and resistance of cancer cells against chemotherapeutic agents. Curcumin, a natural compound extracted from Curcuma longa, has shown strong antioxidant and anticancer properties and also the ability to regulate a wide variety of genes that require activating protein 1 and nuclear factor kappaB (NF-kappaB) activation. In the present study, we examined the inhibitory effect of curcumin on the expression of GSTP1-1 mRNA as well as protein, and we correlated this inhibition with the apoptotic effect of curcumin on K562 leukemia cells. Curcumin efficiently inhibited the tumour necrosis factor alpha- and phorbol ester-induced binding of AP-1 and NF-kappaB transcription factors to sites located on the GSTP1-1 gene promoter. TNFalpha-induced GSTP1-1 promoter activity was also inhibited by curcumin as shown by reporter gene assay. In parallel, curcumin induced pro-caspases 8 and 9 as well as poly ADP ribose polymerase cleavage and thus leading to apoptosis in K562 cells. Our results overall add a novel role for curcumin as this chemoprotective compound could contribute to induce apoptosis by its ability to inhibit the GSTP1-1 expression at the level of transcription.
ANZ J Surg. 2003 Sep;73(9):680-6. : Chemoprevention of gastrointestinal malignancies.
Garcea G, Dennison AR, Steward WP, Berry DP.
University Department of Oncology, The Leicester Royal Infirmary, Leicester, United Kingdom.
gg43@le.ac.uk

BACKGROUND: There has been considerable interest in the use of chemical or dietary agents to suppress or inhibit the development of tumours in the early stages of carcinogenesis. This concept is known as chemoprevention and although the potential for such agents is tremendous, evaluating their clinical benefit is beset with difficulties. AIMS: Using selected agents, such as curcumin and indole-3-carbinol, as examples, the present review will discuss the possible mechanisms of chemoprevention and the problems encountered in developing these agents into clinical drugs. METHODS: A review of the published literature from 1985 to the present day was performed using Medline and Web of Science search engines. Key words used were 'gastrointestinal cancer' and 'chemoprevention'. CONCLUSION: A huge number of agents with possible chemopreventive action has been identified. Pilot trials using molecular signatures of cancer activity can be used to select which agents should be included in large-scale phase III clinical trials. Publications concerning chemoprevention are concentrated in the scientific and oncological literature but surgeons with their greater exposure to premalignant gastrointestinal disease need to be aware of current concepts in this rapidly expanding field. This knowledge would allow collaboration between oncologists and surgeons in clinical trials to further evaluate chemopreventive compounds and ascertain their clinical impact.
Carcinogenesis. 2003 Jul;24(7):1269-79. Epub 2003 May 09.: Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1.
Shishodia S, Potdar P, Gairola CG, Aggarwal BB.
Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Cigarette smoke (CS) is a major cause of a variety of malignancies including cancers of the larynx, oral cavity and pharynx, esophagus, pancreas, kidney, bladder and lung. The signal transduction pathway that mediates the effects of CS is not well understood but nuclear factor-kappa B (NF-kappaB) is probably involved. The gas phase of CS contains free radicals such as superoxide radicals, hydroxyl radicals and hydrogen peroxide, which potentially can activate NF-kappaB. Benzo[a]pyrene, another potent carcinogen of CS, can also activate NF-kappaB, but by an as yet unknown mechanism. Various other agents that activate NF-kappaB are either tumor initiators or tumor promoters, and NF-kappaB activation can block apoptosis, promote proliferation and mediate tumorigenesis. Therefore, NF-kappaB is an ideal target for preventing CS-induced lung carcinogenesis. Thus, agents that abrogate NF-kappaB activation have the potential to suppress lung carcinogenesis. Because curcumin, a diferuloylmethane, is anticarcinogenic, we investigated the effect of this phytochemical on CS-induced NF-kappaB activation and NF-kappaB-regulated gene expression in human non-small cell lung carcinoma cells. Exposure of cells to CS induced persistent activation of NF-kappaB, and pre-treatment with curcumin abolished the CS-induced DNA-binding of NF-kappaB, IkappaBalpha kinase activation, IkBalpha phosphorylation and degradation, p65 nuclear translocation and CS-induced NF-kappaB-dependent reporter gene expression. The inhibition of NF-kappaB activation correlated with suppression of CS-induced NF-kappaB-dependent cyclin D1, cyclooxygenase-2 and matrix metalloproteinase-9 expression. Overall our results indicate that CS-induced NF-kappaB activation and NF-kappaB-regulated gene expression in human non-small cell lung carcinoma cells is suppressed by curcumin through suppression of IkappaBalpha kinase.
: Int J Mol Med. 2003 Jul;12(1):17-24. : Structure of curcumin in complex with lipoxygenase and its significance in cancer.
Skrzypczak-Jankun E, Zhou K, McCabe NP, Selman SH, Jankun J.
Department of Urology, Urology Research Center, Medical College of Ohio, Toledo, OH 43614-5807, USA.

Scientific research provides documented evidence that fatty acid metabolites have profound impact on carcinogenesis. Intervention into dioxygenase pathways might therefore effect development, metastasis and progression of many types of cancers. This work delivers the first 3D structural data and explains how curcumin interacts with the fatty acid metabolizing enzyme, soybean lipoxygenase. Curcumin binds to lipoxygenase in a non-competitive manner. Trapped in that complex, it undergoes photodegradation in the X-rays, but utilizes enzyme catalytic ability to form the peroxy complex Enz-Fe-O-O-R as 4-hydroperoxy-2-methoxy-phenol, that later transforms into 2-methoxycyclohexa-2,5-diene-1,4-dione. Our observations about this radiation and time-dependent inhibition add new information to the role that curcumin might play in cancer prevention and treatment.
Toxicol In Vitro. 2003 Jun;17(3):323-33. : Curcumin inhibited the arylamines N-acetyltransferase activity, gene expression and DNA adduct formation in human lung cancer cells (A549).
Chen YS, Ho CC, Cheng KC, Tyan YS, Hung CF, Tan TW, Chung JG.
Department of Nutrition, China Medical College, 91 Hsueh-Shih Road, 404, ROC, Taichung, Taiwan.

It is well known that N-acetyltransferase (NAT) plays an important role in the arylamine metabolism. We analysed the response of A549 human lung cancer cells for N-acetylation of 2-aminofluorene (AF) to curcumin. After curcumin treatment, the NAT activity was examined by HPLC, AF-DNA adduct formation was examined by HPLC, and NAT gene expression by polymerase chain reaction were detected. The NAT activity in the human A549 cells and cytosols was suppressed by curcumin in a dose-dependent manner. The results also demonstrated that gene expression (NAT1 mRNA) in human lung A549 tumor cells was inhibited and decreased by curcumin. After the incubation of human lung A549 tumor cells with AF with or without curcumin co-treatment, the cells were recovered and DNA was prepared and hydrolyzed to nucleotides. The adducted nucleotides were extracted into butanol and analyzation of AF-DNA adducts was done by HPLC. The results also demonstrated that curcumin decreases AF-DNA adduct formation in the human lung A549 tumor cells.
Br J Cancer. 2003 May 6;88(9):1480-3. : Age-related difference in susceptibility of Apc(Min/+) mice towards the chemopreventive efficacy of dietary aspirin and curcumin.
Perkins S, Clarke AR, Steward W, Gescher A.
Cancer Biomarkers and Prevention Group, Department of Oncology, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK.

The nonsteroidal anti-inflammatory drug aspirin and the spice curcumin retard adenoma formation when administered long-term to Apc(Min/+) mice, a model of human familial adenomatous polyposis coli. Both agents interfere with cyclooxygenase activity. When aspirin is administered to Apc(Min/+) mice only postweaning, but not before, it is inefficacious, while curcumin given postweaning is active. Here the hypothesis was tested that dietary aspirin (0.05%) or curcumin (0.2%) prevent or delay adenoma formation in offsprings when administered to Apc(Min/+) mothers and up to the end of weaning, but not afterwards. Whereas curcumin was without effect when administered in this way, aspirin reduced numbers of intestinal adenomas by 21%. When aspirin given up to the end of weaning was combined with curcumin administered from the end of weaning for the rest of the animals' lifetime, intestinal adenoma numbers were reduced by 38%. The combination was not superior to intervention postweaning with curcumin alone. These results show that aspirin exerts chemopreventive activity in the Apc(Min/+) mouse during tumour initiation/early promotion, while curcumin is efficacious when given at a later stage of carcinogenic progression. Thus, the results suggest that in this mouse model aspirin and curcumin act during different 'windows' of neoplastic development
Xenobiotica. 2003 Apr;33(4):357-63. : Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues.
Vietri M, Pietrabissa A, Mosca F, Spisni R, Pacifici GM.
Department of Neurosciences, Section of Pharmacology, Medical School, Via Roma 55, I-56126 Pisa, Italy.

1. Curcumin has anti-carcinogen effects and is under clinical evaluation as a potential colon cancer chemopreventive agent. The first aim was to see whether curcumin inhibited phenol sulfotransferase (SULT1A1) and, if so, to study the variability of the IC(50) of curcumin for SULT1A1 in 50 human liver samples. For comparative purposes, the inhibition of catechol sulfotransferase (SULT1A3) in five human liver specimens was studied. The second aim was to measure the IC(50) of curcumin against SULT1A1 in five samples of human duodenum, colon, kidney and lung. 2. Curcumin was a potent inhibitor of SULT1A1 in human liver; the mean +/- SD and median of IC(50) were 14.1 +/- 7.3 nM and 12.8 nM, respectively. The IC(50) ranged from 6.2 to 30.6 nM between the 5th and 95th percentiles and the fold of variation was 4.9. The distribution of IC(50) was positively skewed (skewness 1.2) and deviated from normality (p = 0.0004). 3. Curcumin inhibited human SULT1A3, and the inhibition was studied in five liver specimens with an IC(50) of 4324 +/- 1026 nM. This inhibition was greater than the IC(50) of curcumin for SULT1A1 (p < 0.0001). 4. In the extrahepatic tissues, the IC(50) of curcumin for SULT1A1 was 25.9 +/- 4.8 nM (duodenum), 25.4 +/- 6.8 nM (colon), 23.4 +/- 2.2 nM (kidney) and 25.6 +/- 5.6 nM (lung). Inhibition in these tissues is greater than that of curcumin for SULT1A1 in human liver (p < 0.0001). 5. In conclusion, curcumin is a potent inhibitor of SULT1A1 in human liver, duodenum, colon, kidney and lung. The IC(50) of curcumin for SULT1A1 varied 4.9-fold in human liver. The comparison of the present data with those of the literature revealed that the IC(50) of curcumin in the liver and extrahepatic tissues is one order of magnitude lower that the peak serum concentration of curcumin after therapeutic doses of 4 g to humans.
Am J Physiol Gastrointest Liver Physiol. 2003 Jan;284(1):G85-95. : Curcumin ameliorates ethanol and nonethanol experimental pancreatitis.
Gukovsky I, Reyes CN, Vaquero EC, Gukovskaya AS, Pandol SJ.
Research Center for Alcoholic Liver and Pancreatic Diseases and Department of Medicine, University of California, Los Angeles and Veterans Affairs Greater Los Angeles Healthcare System, 90073, USA.
igukovsk@ucla.edu

Treatments for pancreatitis are limited. Activation of transcription factor NF-kappaB, a key regulator of inflammatory molecule expression, is an early event in experimental pancreatitis and correlates with the inflammatory response. We report here that curcumin, a natural phytochemical known to inhibit NF-kappaB and activator protein (AP)-1, another important proinflammatory transcription factor, ameliorates pancreatitis in two rat models. In both cerulein pancreatitis and pancreatitis induced by a combination of ethanol diet and low-dose CCK, curcumin improved the severity of the disease as measured by a number of parameters (histology, serum amylase, pancreatic trypsin, and neutrophil infiltration). Curcumin markedly inhibited NF-kappaB and AP-1 activation, assessed by DNA binding and degradation of inhibitory IkappaB proteins, and the induction of mRNAs for cytokines IL-6 and TNF-alpha, the chemokine KC, and inducible nitric oxide synthase in pancreas. Curcumin also blocked CCK-induced NF-kappaB and AP-1 activation in isolated pancreatic acini. Our findings indicate that blocking key signals of the inflammatory response ameliorates pancreatitis in both ethanol and nonethanol models. They suggest that curcumin, which is currently in clinical trials for cancer prevention, may be useful for treatment of pancreatitis.
Wound Repair Regen. 1999 Sep-Oct;7(5):362-74. : Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice.
Sidhu GS, Mani H, Gaddipati JP, Singh AK, Seth P, Banaudha KK, Patnaik GK, Maheshwari RK.
Center for Combat and Life Sustainment Research, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.
rmaheshwari@usuhs.mil

Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-beta1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-beta1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.
Plant Foods Hum Nutr. 2002 Winter;57(1):41-52. : Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats.
Arun N, Nalini N.
Department of Biochemistry, Annamalai University, Annamalainagar, Tamil Nadu, India.

In the traditional system of medicine, Ayurveda, several spices and herbs are thought to possess medicinal properties. Among the spices, turmeric rhizomes (Curcuma longa. Linn.) are used as flavoring and coloring agents in the Indian diet everyday. In this research, we studied the effect of turmeric and its active principle, curcumin, on diabetes mellitus in a rat model. Alloxan was used to induce diabetes. Administration of turmeric or curcumin to diabetic rats reduced the blood sugar, Hb and glycosylated hemoglobin levels significantly. Turmeric and curcumin supplementation also reduced the oxidative stress encountered by the diabetic rats. This was demonstrated by the lower levels of TBARS (thiobarbituric acid reactive substances), which may have been due to the decreased influx of glucose into the polyol pathway leading to an increased NADPH/NADP ratio and elevated activity of the potent antioxdiant enzyme GPx. Moreover, the activity of SDH (sorbitol dehydrogenase), which catalyzes the conversion of sorbitol to fructose, was lowered significantly on treatment with turmeric or curcumin. These results also appeared to reveal that curcumin was more effective in attenuating diabetes mellitus related changes than turmeric.
Int J Food Sci Nutr. 1996 Jan;47(1):55-9. : Influence of dietary spices or their active principles on digestive enzymes of small intestinal mucosa in rats.
Platel K, Srinivasan K.
Department of Biochemistry & Nutrition, Central Food Technological Research Institute, Mysore, India.
A few common spices or their active principles, were examined for their possible influence on digestive enzymes of intestinal mucosa in experimental rat. The animals were fed the following diets for 8 weeks: control, curcumin (0.5%), capsaicin (15 mg%), piperine (20 mg%), ginger (50 mg%), cumin (1.25%), fenugreek (2%), mustard (250 mg%) and asafoetida (250 mg%). Dietary curcumin, capsaicin, piperine and ginger prominantly enhanced intestinal lipase activity and also the disaccharidases sucrase and maltase. Dietary cumin, fenugreek, mustard and asafoetida brought about decreases in the levels of phosphatases and sucrase. The positive influences of a good number of spices on these terminal enzymes of digestive process could be an additional feature of species that are generally well recognized to stimulate digestion.
Nahrung. 2002 Dec;46(6):394-8. Related Articles, Links Digestive stimulant action of three Indian spice mixes in experimental rats. Platel K, Rao A, Saraswathi G, Srinivasan K. Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore-570 013, India.
The present study examined the favourable influence of three spice mixes derived from a few commonly consumed spices of known digestive stimulant action on digestive enzymes of pancreas and small intestine, and on bile secretion and composition in experimental rats. The common ingredients of these mixes were coriander, turmeric, red chilli, black pepper and cumin, while the spice mix II additionally had ginger, and spice mix III contained onion. All the three spice mixes favourably enhanced the activities of pancreatic lipase, chymotrypsin and amylase when consumed during the diet. In addition, these spice mixes brought about a pronounced stimulation of bile flow and of bile acid secretion. Among the three spice mixes examined, spice mix III which is customized so as to include spices that are desirable from the point of view of stimulation of digestion, had the highest stimulatory influence particularly on bile secretion, bile acid output and the activities of pancreatic enzymes. While activities of pancreatic lipase, amylase and chymotrypsin were elevated by 40, 16 and 77%, respectively, the bile volume as well as the bile acid secretion were almost doubled in spice mix III treatment. The higher secretion of bile especially with an elevated level of bile acids and a beneficial stimulation of pancreatic digestive enzymes, particularly of lipase could probably be the two mechanisms by which these combinations of spices aid in digestion.
Mol Cell Biochem. 2002 Jan;229(1-2):19-23. : Inhibition of human low density lipoprotein oxidation by active principles from spices.
Naidu KA, Thippeswamy NB.
Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India. Kanaidu@mailcity.com

Spice components and their active principles are potential antioxidants. In this study we examined the effect of phenolic and non-phenolic active principles of common spices on copper ion-induced lipid peroxidation of human low density lipoprotein (LDL) by measuring the formation of thiobarbituric acid reactive substance (TBARS) and relative electrophoretic mobility (REM) of LDL on agarose gel. Curcumin, capsaicin, quercetin, piperine, eugenol and allyl sulfide inhibited the formation of TBARS effectively through out the incubation period of 12 h and decreased the REM of LDL. Spice phenolic active principles viz. curcumin, quercetin and capsaicin at 10 microM produced 40-85% inhibition of LDL oxidation at different time intervals while non-phenolic antioxidant allyl sulfide was less potent in inhibiting oxidation of LDL. However, allyl sulfide, eugenol and ascorbic acid showed pro-oxidant activity at lower concentrations (10 microM) and antioxidant activity at higher concentrations (50 microM) only. Among the spice principles tested quercetin and curcumin showed the highest inhibitory activity while piperine showed least antioxidant activity at equimolar concentration during initiation phase of oxidation of LDL. The inhibitory effect of curcumin, quercetin and capsaicin was comparable to that of BHA, but relatively more potent than ascorbic acid. Further, the effect of curcumin, quercetin, capsaicin and BHA on initiation and propagation phases of LDL oxidation showed that curcumin significantly inhibited both initiation and propagation phases of LDL oxidation, while quercetin was found to be ineffective at propagation phase. These data suggest that the above spice active principles, which constitute about 1-4% of above spices, are effective antioxidants and offer protection against oxidation of human LDL
Southeast Asian J Trop Med Public Health. 2000;31 Suppl 1:178-82. : Antifungal activity of Curcuma longa grown in Thailand.
Wuthi-udomlert M, Grisanapan W, Luanratana O, Caichompoo W.
Department of Microbiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Curcuma longa Linn. or turmeric (Zingiberaceae) is a medicinal plant widely used and cultivated in tropical regions. According to Thai traditional texts, fresh and dried rhizomes are used as peptic ulcer treatment, carminatives, wound treatment and anti-inflammatory agent. Using hydro distillation, 1.88% and 7.02% (v/w) volatile oils were extracted from fresh and dried rhizomes, respectively, and 6.95% (w/w)crude curcuminoids were extracted from dried rhizomes. Dried powder was extracted with 95% ethanol and yielded 29.52% (w/w) crude ethanol extract composed of curcumin (11.6%), demethoxycurcumin (10.32%) and bisdemethoxycurcumin (10.77%). These extracts were tested for antifungal activity by agar disc diffusion method against 29 clinical strains of dermatophytes. It was found that crude ethanol extract exhibited an inhibition zone range of 6.1 to 26.0 mm. There was no inhibition activity from crude curcuminoids while curcumin, demethoxycurcumin and bisdemethoxycutcumin gave different inhibition zone diameters ranging from 6.1 to 16.0 mm. Although antifungal activity of undiluted freshly distilled oil and 18-month-old oil revealed some differences, the inhibition zone diameters for both extracts varied within 26.1 to 46.0 mm. With 200 mg/ml ketoconazole, the activities of the standard agent were similar to the oil, both freshly distilled and 18-month-old, but were significantly different from those of curcuminoid compounds and crude ethanol extracts (p < 0.01). Turmeric oil was also tested for its minimum inhibitory concentration (MIC) by broth dilution method. The MICs of freshly distilled and 18-month-old oils were 7.8 and 7.2 mg/ml respectively.
J Ethnopharmacol. 1995 Dec 15;49(3):163-9. : Antifungal activity of turmeric oil extracted from Curcuma longa (Zingiberaceae).
Apisariyakul A, Vanittanakom N, Buddhasukh D.
Department of Pharmacology, Chiang Mai University, Thailand.

Turmeric oil and curcumin, isolated from Curcuma longa L., were studied against fifteen isolates of dermatophytes, four isolates of pathogenic molds and six isolates of yeasts. The inhibitory activity of turmeric oil was tested in Trichophyton-induced dermatophytosis in guinea pigs. The results showed that all 15 isolates of dermatophytes could be inhibited by turmeric oil at dilutions of 1:40-1:320. None of the isolates of dermatophytes were inhibited by curcumin. The other four isolates of pathogenic fungi were inhibited by turmeric oil at dilutions of 1:40-1:80 but none were inhibited by curcumin. All six isolates of yeasts tested proved to be insensitive to both turmeric oil and curcumin. In the experimental animals, turmeric oil (dilution 1:80) was applied by dermal application on the 7th day following dermatophytosis induction with Trichophyton rubrum. An improvement in lesions was observed in 2-5 days and the lesions disappeared 6-7 days after the application of turmeric oil.