B. Biological effects

1. Inflammatory Bowel Disease

• Numerous therapies used for inflammatory bowel disease (IBD) target the transcription factor NF-kappaB, which is involved in the production of cytokines and chemokines integral for inflammation. The authors show that curcumin, is able to attenuate colitis in the dinitrobenzene sulfonic acid (DNB)-induced murine model of colitis. They also show that the immunohistochemical signal is dramatically attenuated at the level of the mucosa by curcumin. They conclude that curcumin is able to attenuate experimental colitis through a mechanism correlated with the inhibition of the activation of NF-kappaB and effects a reduction in the activity of p38 MAPKwith therapeutic implications for human IBD.
  
  Source: Am J Physiol Gastrointest Liver Physiol. 2003 Jul;285(1):G235-43. Epub 2003 Mar 13.
  Title: Curcumin attenuates DNB-induced murine colitis.
  Authors: Salh B, Assi K, Templeman V, Parhar K, Owen D, Gomez-Munoz A, Jacobson K.
  
  
• The authors explored the mechanism of modulation of intestinal mucosal inflammatory factors by curcumin, the inhibitor of the transcriptional factor nuclear factor -kappaB (NF-kappaB), in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis, and screened for a targeted therapeutic agent for treatment of inflammatory bowel disease Rats with TNBS-induced colitis were fed with diet containing 2.0% curcumin (treatment group), 0.5% sulfasalazine (SASP, positive control group), and normal diet (model group and negative control group). Changes in colonic mucosal histological scores were evaluated and the cytokine mRNA expressions in the colonic tissue assessed by semiquantitative reverse transcriptional PCR (RT-PCR). Treatment with curcumin ameliorated the histopathologic signs in rats with TNBS-induced intestinal inflammation. The authors concluded that Curcumin could modulate the expressions of IL-1beta and IL-10 mRNA in murine model of IBD, which suggests the potential of curcumin as a targeted therapeutic agent for IBD.
  
  Source: Pubmed Abstract of Article in Chinese from: Di Yi Jun Yi Da Xue Xue Bao. 2004 Dec;24(12):1353-8.
  Title: Modulation of intestinal mucosal inflammatory factors by curcumin in rats with colitis.
  Authors: Jian YT , Wang JD, Mai GF, Zhang YL, Lai ZS.
  
  
• Dose-response studies revealed that pretreatment of mice with curcumin (50 mg kg(-1) daily i.g. for 10 days) significantly ameliorated the appearance of diarrhoea and the disruption of colonic architecture in mice with induced colitis. Higher doses (100 and 300 mg kg(-1)) had comparable effects. In curcumin-pretreated mice, there was a significant reduction in the degree of both neutrophil infiltration (measured as decrease in myeloperoxidase activity) and lipid peroxidation (measured as decrease in malondialdehyde activity) in the inflamed colon as well as decreased serine protease activity. Curcumin also reduced the levels of nitric oxide (NO) and O(2)(-) associated with the favourable expression of Th1 and Th2 cytokines and inducible NO synthase. Consistent with these observations, nuclear factor-kappaB activation in colonic mucosa was suppressed in the curcumin-treated mice. These findings suggest that curcumin exerts beneficial effects in experimental colitis and may, therefore, be useful in the treatment of IBD.
  
  Source: Br J Pharmacol. 2003 May;139(2):209-18.
  Title: Curcumin, the major component of food flavor turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis.
  Authors: Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK.
  

2. Curcumin and osteoarthiritis

• P54FP is an extract of Indian and Javanese turmeric, Curcuma domestica and Curcuma xanthorrhiza respectively, which contains a mixture of active ingredients including curcuminoids and essential oils. A randomised, double-blind, placebo-controlled, parallel group clinical trial of P54FP as a treatment for osteoarthritis of the canine elbow or hip was conducted to assess its efficacy and safety. Sixty-one client-owned dogs with osteoarthritis were recruited through first-opinion practices and examined at a single centre. After a two-week wash-out period, they were randomly allocated to receive P54FP or a placebo orally twice daily for eight weeks, and were re-examined after four, six and eight weeks of treatment. The investigators' overall assessment showed a statistically significant treatment effect in favour of P54FP (P=0.012), but the owners' assessment just failed to reach statistical significance (P=0.063). No serious adverse effects were recorded, but two P54FP-treated dogs and four placebo-treated dogs werewithdrawn from the study because their condition deteriorated

Source: Vet Rec. 2003 Apr 12;152(15):457-60.
Title: Randomised, double-blind, placebo-controlled parallel group study of P54FP for the treatment of dogs with osteoarthritis.
Authors: Innes JF, Fuller CJ, Grover ER, Kelly AL , Burn JF.

3. Antitumor /Anticancer/Antimutagenic

• In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies, and discusses the mechanism of action of curcumin.
  
  Source: Anticancer Res. 2003 Jan-Feb;23(1A):363-98.
  Title: Anticancer potential of curcumin: preclinical and clinical studies.
  Authors: Aggarwal BB, Kumar A, Bharti AC.
  
  
• Effect of aqueous extracts of turmeric, cloves, pepper, chili, cinnamon, onion and also their respective active principles viz., curcumin, eugenol, piperine, capsaicin, cinnamaldehyde, quercetin, and allyl sulfide were tested on human PMNL 5-LO activity byspectrophotomeric and HPLC methods. The formation of 5-LO product 5-HETE was significantly inhibited in a concentration-dependent manner by aqueous extracts of spices and the respective active principles. Quercetin, eugenol and curcumin with one or more phenolic ring and methoxy groups in their structure showed high inhibitory effect, while the non-phenolic spice principle allyl sulfide showed least inhibitory effect on 5-LO. The inhibitory effect of quercetin, curcumin and eugenol was similar to that of synthetic 5-LO inhibitors-phenidone and NDGA. These findings clearly suggest that phenolic compounds present in spices might have physiological role in modulating 5-LO pathway.
  
  Source: Prostaglandins Leukot Essent Fatty Acids. 2004 Jun;70(6):521-8.
  Title: Spice phenolics inhibit human PMNL 5-lipoxygenase.
  Authors: Prasad NS , Raghavendra R, Lokesh BR, Naidu KA.
  
  
• The effects of curcumin on 12-O- tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2) in female ICR mouse skin were assessed. Topical application of the dorsal skin of female ICR mice with 10 nmol TPA led to maximal induction of cox-2 mRNA and protein expression at approximately 1 and 4 h, respectively. When applied topically onto shaven backs of mice 30 min prior to TPA, curcumin inhibited the expression of COX-2 protein in a dose-related manner. Taken together, suppression of COX-2 expression and NF-kappaB activation may represent molecular mechanisms underlying previously reported antitumor promoting effects of curcumin in mouse skin tumorigenesis.
  
  Source: Carcinogenesis. 2003 Sep;24(9):1515-24. Epub 2003 Jul 04.
  Title: Curcumin inhibits phorbol ester-induced expression of cyclooxygenase-2 in mouse skin through suppression of extracellular signal-regulated kinase activity and NF-kappaB activation.
  Authors: Chun KS, Keum YS, Han SS, Song YS, Kim SH, Surh YJ.
  
  
• Based on the hypothesis that natural agents capable of modulating both lipoxygenase and COX may advance the efficacy of cancer therapy, an overview and discussion is presented of dietary modifications and selected nutritional and botanical agents (notably, omega-3 fatty acids, antioxidants, boswellia, bromelain, curcumin, and quercetin) that favorably influence eicosanoid production.
  
  Source: Integr Cancer Ther. 2002 Mar;1(1):7-37; discussion 37.
  Title: Nutritional and botanical modulation of the inflammatory cascade--eicosanoids, cyclooxygenases, and lipoxygenases--as an adjunct in cancer therapy.
  Authors: Wallace JM
  
  
• Cancer rates in India are lower than those seen in Western countries, but are rising with increasing migration of rural population to the cities, increase in life expectancy and changes in lifestyles. In India , rates for oral and oesophageal cancers are some of the highest in the world. In contrast, the rates for colorectal, prostate, and lung cancers are one of the lowest. Studies of Indian immigrants in Western societies indicate that rates of cancer and other chronic diseases, such as coronary heart disease and diabetes, increase dramatically after a generation in the adopted country. Change of diet is among the factors that may be responsible for the changing disease rates. Of particular interest for cancer prevention is the role of turmeric (curcumin), an ingredient in common Indian curry spice. Researchers also have investigated cumin, chilies, kalakhar, Amrita Bindu, and various plant seeds for their apparent cancer preventive properties.
  
  Source: J Postgrad Med. 2003 Jul-Sep;49(3):222-8.
  Title: Cancer risk and diet in India .
  Authors: Sinha R, Anderson DE , McDonald SS, Greenwald P.
  
  
• The selection of micronutrients, defined as essential and nonessential dietary components consumed in minute quantities, for testing in clinical chemoprevention trials is based on the totality of evidence arising from epidemiologic, in vitro, animal, and clinical studies. Those micronutrients that surface with chemopreventive potential, in terms of high efficacy and low toxicity, in early-phase clinical studies are then candidates for large-scale, randomized clinical chemoprevention trials with cancer endpoints. Micronutrients currently being examined in National Cancer Institute (NCI)-sponsored phase I, II, or III chemoprevention trials for prostate, breast, and colon cancers include isoflavones, lycopene, selenized yeast, selenomethionine, selenium, vitamin E, perillyl alcohol, folic acid, vitamin D, calcium, and curcumin.
  
  Source: Cancer Metastasis Rev. 2002;21(3-4):217-30.
  Title: Micronutrients in cancer chemoprevention.
  Authors: Greenwald P, Milner JA, Anderson DE , McDonald SS.
  
  
• Heterocyclic amines (HCAs) are potent mutagens generated during the cooking of meat and fish, and several of these compounds produce tumors in conventional experimental animals. This review describes several of the more recent reports in which novel animal models were used to examine HCA-induced mutagenesis and carcinogenesis in vivo, including a number of studies which assessed the inhibitory activities of chemopreventive agents such as 1,2-dithiole-3-thione, conjugated linoleic acids, tea, curcumin, chlorophyllin-chitosan, and sulindac.
  
  Source: J Biochem Mol Biol. 2003 Jan 31;36(1):35-42.
  Title: Use of transgenic and mutant animal models in the study of heterocyclic amine-induced mutagenesis and carcinogenesis.
  Author: Dashwood RH.
  
  
• Smoke Shield is a formulation designed to reduce smoke related mutagenicity And toxicity in the population. Smoke Shield contains a dual extract of turmeric (Curcuma longa) obtained by supercritical CO2 gas extraction and post-supercritical hydroethanolic extraction together with extracts of green tea and other spices, whose presence synergistically increases the activity of turmeric. Smoke Shield was found to significantly inhibit the mutagenicity induced by tobacco extract to Salmonella typhimurium TA102. Smoke Shield was also found to inhibit the urinary mutagenicity of rats treated with the benzo[a]pyrene and tobacco extract. Moreover, Smoke Shield administration was found to inhibit the urinary mutagenicity in smokers. These results indicate that Smoke Shield could inhibit mutagenic response in vitro and in vivo produced by several kinds of mutagens present in our atmosphere
  
  Source: J Exp Clin Cancer Res. 2004 Mar;23(1):61-8.
  Title: Antimutagenicity of herbal detoxification formula Smoke Shield against environmental mutagens.
  Authors: Kuttan R, Kuttan G, Joseph S, Ajith TA, Mohan M, Srimal RC.
  
  
• Multidrug resistance (MDR) is a phenomenon that is often associated with decreased intracellular drug accumulation in patient's tumor cells resulting from enhanced drug efflux. It is related to the overexpression of a membrane protein, P-glycoprotein (Pgp-170), thereby reducing drug cytotoxicity.
  Natural curcuminoids, pure curcumin, demethoxycurcumin and bisdemethoxycurcumin, isolated from turmeric (Curcuma longa Linn), were compared for their potential ability to modulate the human MDR-1 gene expression in multidrug resistant human cervical carcinoma cell line, KB-V1 by Western blot analysis and RT-PCR. The results indicated that bisdemethoxycurcumin is the most active of the curcuminoids present in turmeric for modulation of MDR-1 gene. The modulation of MDR-1 expression may be an attractive target for new chemosensitizing agents.
  
  Source: BMC Cancer. 2004 Apr 17;4(1):13.
  Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids.
  Limtrakul P, Anuchapreeda S, Buddhasukh D.
  
  
• Gene deletion studies have shown that receptor activator of NF-kappabligand (RANKL) is one of the critical mediators of steoclastogenesis. Curcumin inhibited both RANKL- and TNF-induced osteoclastogenesis and pit formation. Curcumin suppressed osteoclastogenesis maximally when added together with RANKL and minimally when it was added 2 days after RANKL. The results indicated treatment with curcumin inhibits both the NF-kappaB activation and osteoclastogenesis induced by RANKL.
  
  Source: J Immunol. 2004 May 15;172(10):5940-7.
  Title: Curcumin (diferuloylmethane) inhibits receptor activator of NF-kappab ligand-induced NF-kappaB activation in osteoclast precursors and suppresses osteoclastogenesis.
  Authors: Bharti AC, Takada Y, Aggarwal BB.
  
  
• Incidence of cancer at different sites may be related to oxidative damage to host genome by genotoxicants. These oxidative actions may be modified by phytochemicals present in foods. The non-nutritive dietary constituents which possess antimutagenic property appear to be promising chemopreventive agents.
  This study reports the protective effect of curcumin on B(a)P induced DNA damage in human peripheral blood lymphocyte cells.
  The study group consisted of 10 male smokers, 10 non-smokers and 10 non-smoking females aged between 25 and 45. The DNA damage was assessed using comet assay. In all the groups curcumin showed a dose-dependent inhibitory effect. The effect appeared to be sex dependent.
  
  Source: Mutat Res. 2004 Feb 14;557(2):203-13.
  Title: Inhibition of B(a)P induced strand breaks in presence of curcumin.
  Authors: Polasa K, Naidu AN, Ravindranath I, Krishnaswamy K.
  
  
• In this study the authors examined the modulatory effects of turmeric on nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in rats. NDEA-treated rats receiving 1 or 5% turmeric before, during and after carcinogen exposure showed significant decrease in number of gamma glutamyl transpeptidase (GGT) positive foci and decrease in the incidence of NDEA-induced focal dysplasia (FD) and hepatocellularcarcinomas.
  
  Source: Toxicol Lett. 2003 Mar 20;139(1):45-54.
  Title: Inhibition of nitrosodiethylamine-induced hepatocarcinogenesis by dietary turmeric in rats.
  Authors: Thapliyal R, Naresh KN, Rao KV, Maru GB.
  
  
• Dose-response studies demonstrated that curcumin concentrations of or=25 micro M were cytotoxic for oral SCC cells. Curcumin increased both expression (reverse transcription-PCR analyses) and function (high-performance liquid chromatography determination of ethoxyresorufin metabolism) of cytochrome P-450 (CYP) 1A1 and/or CYP1B1. Because CYP1A1 is one of the primary carcinogen-activating enzymes in oral mucosa, the use of curcumin as an oral cavity chemopreventive agent could have significant clinical impact via its ability to inhibit carcinogen bioactivation.
  
  Source: Cancer Res. 2002 Oct 1;62(19):5451-6.
  Title: Curcumin activates the aryl hydrocarbon receptor yet significantly inhibits (-)-benzo(a)pyrene-7R-trans-7,8-dihydrodiol bioactivation in oral squamous cell carcinoma (SCC) cells and oral mucosa.
  Authors: Rinaldi AL, Morse MA, Fields HW, Rothas DA, Pei P, Rodrigo KA, Renner RJ, Mallery SR.
  
  
• In the present study the effect of curcumin on the development of altered hepatic foci(AHF), by using a medium term liver bioassay, has been evaluated.
  The curcumin administration was found to restore the normal levels of the enzymes glutathione S-transferase and g-glutamyl transferase in rat liver following DEN-AAF exposure. Similarly, a significant protection was provided by curcumin in the enzyme-deficient foci for the adenosine triphosphatase-, alkaline phosphatase-, and glucose-6-phosphatase-treated groups in comparison to the DEN-AAF-treated group. These results show that curcumin can effectively suppress the DEN-induced development of AHF in rat liver.
  
  Source: Nutr Cancer. 2003;45(1):53-9.
  Title: Suppression of altered hepatic foci development by curcumin in wistar rats.
  Authors: Shukla Y, Arora A.
  
  
• This report discusses the mechanism of EGCG and curcumin action in regulating expression of involucrin, a marker of keratinocyte differentiation.
  
  Source: Biochem Pharmacol. 2004 Sep 15;68(6):1125-31. Title: Antioxidants regulate normal human keratinocyte differentiation. Authors: Eckert RL, Crish JF, Efimova T, Balasubramanian S.
  
  The inhibitory effect of curcumin and its synergism with 5-fluorouracil (5-FU) on the growth of the AGS human gastric carcinoma cell line was examined. Combining curcumin with 5-FU significantly increased growth inhibition of AGS cells compared with either curcumin or 5-FU alone (P <.05), suggesting synergistic actions of the two drugs. Curcumin may be useful for the treatment of gastric carcinoma, especially in conjunction with 5-FU.
  
  Source: J Med Food. 2004 Summer;7(2):117-21.
  Title: Curcumin inhibits the growth of AGS human gastric carcinoma cells in vitro and shows synergism with 5-fluorouracil.
  Authors: Koo JY, Kim HJ, Jung KO, Park KY.
  
  
• A series of novel curcumin analogs were synthesized and screened for anti-cancer and anti-angiogenesis activities at Emory University and at the National Cancer Institute (NCI).
  
  Source: Bioorg Med Chem. 2004 Jul 15;12(14):3871-83. Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents.
  Adams BK, Ferstl EM, Davis MC, Herold M, Kurtkaya S, Camalier RF, Hollingshead MG, Kaur G, Sausville EA, Rickles FR, Snyder JP, Liotta DC, Shoji M.
  

4. Gastroprotective /antiulcer :

• Matrix metalloproteinases (MMPs) are suggested to play a critical role in extracellular matrix (ECM) degradation and remodeling during inflammation and wound healing processes. The anti-inflammatory and antioxidant properties of curcumin, an active component of turmeric suggest that curcumin may exert anti-ulcer activity either through scavenging reactive oxygen species (ROS) or by regulating MMP activity, or both. The authors studied the effect of curcumin in indomethacin-induced gastric ulcer. The results show that curcumin exhibits potent antiulcer activity in acute ulcer in rat model by preventing glutathione depletion, lipid peroxidation and protein oxidation, and denudation of epithelial cells during damage of gastric lumen is reversed by curcumin through re-epithelialization. The results also revealed that both oral and intraperitoneal administration of curcumin blocks gastric ulceration in a dose dependent manner. It accelerates the healing process and protects gastric ulcer through attenuation of MMP-9 activity and amelioration of MMP-2 activity.
  
  Source: J Biol Chem. 2004 Dec 22; [Epub ahead of print]
  Title: Curcumin regulates expression and activity of matrix metalloproteinases-9 and -2 during prevention and healing of indomethacin-induced gastric ulcer.
  Authors: Swarnakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV.

5. Wound healing :

• Irradiation caused significant delay in wound contraction and healing times in mice. However, treatment with curcumin resulted in a dose-dependent increase in contraction when compared with a control. Greatest contraction was observed for 100 mg/kg curcumin, with statistically significant results at days three (p &lt; 0.009), six (p &lt; 0.05) and nine (p &lt; 0.05) post-irradiation for this dose. Complete healing was achieved by day 23 post-irradiation in the curcumin-treated irradiation group.
  Source: J Wound Care. 2004 Mar;13(3):107-9.
  Title: Effect of curcumin on radiation-impaired healing of excisional wounds in mice.
  Authors: Jagetia GC, Rajanikant GK.
  
  
• An improvement in the quality of wound healing was attempted by slow delivery of antioxidants like curcumin from collagen, which also acts as a supportive matrix for the regenerative tissue. Curcumin incorporated collagen matrix (CICM) treated groups were compared with control and collagen treated rats. Biochemical parameters and histological analysis revealed that increased wound reduction, enhanced cell proliferation and efficient free radical scavenging in CICM group. This study provides a rationale for the topical application of CICM as a feasible and productive approach to support dermal wound healing.
  
  Source: Biomaterials. 2004 May;25(10):1911-7.
  Title: Dermal wound healing processes with curcumin incorporated collagen films.
  Authors: Gopinath D, Ahmed MR, Gomathi K, Chitra K, Sehgal PK , Jayakumar R.

6. Cystic fibrosis

• Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. The authors postulate that curcumin treatment may be able to correct defects associated with the homozygous expression of DeltaF508 CFTR.
  
  Source: Science. 2004 Apr 23;304(5670):600-2.
  Title: Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.
  Authors: Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Glockner-Pagel J, Canny S, Du K, Lukacs GL, Caplan MJ.
  
  Curcumin was found to cause apoptosis in scleroderma lung fibroblasts (SLF), but not in normal lung fibroblasts (NLF). These observations suggest that curcumin may have therapeutic value in treating scleroderma, just as it has already been shown to protect rats from lung fibrosis induced by a variety of agents.
  
  Source: Am J Respir Cell Mol Biol. 2004 Jan 23 [Epub ahead of print]
  Title: Curcumin-Induced Apoptosis in Scleroderma Lung Fibroblasts: Role of Protein Kinase C {epsilon}
  Authors: Tourkina E, Gooz P, Oates JC, Ludwicka-Bradley A, Silver RM, Hoffman S.
  
  The authors report that that berberine, curcumin and hesperidin can increase mucin release by directly acting on airway mucin-secreting cells and suggest that these agents be further studied for possible use as mild expectorants during the treatment of chronic airway diseases
  
  Source: Planta Med. 2003 Jun;69(6):523-6.
  Title: Effects of baicalein, berberine, curcumin and hesperidin on mucin release from airway goblet cells.
  Authors: Lee CJ, Lee JH, Seok JH, Hur GM, Park YC, Seol IC, Kim YH.
  

• Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. (From the article: The finding that curcumin causes contraction of the gall bladder indicates that it may be potentially useful in preventing gall bladder stone formation, and may be used clinically to enhance biliary flow or to push out biliary sludge in the gall bladder - cholekinetic effects )
  
  Source: Asia Pac J Clin Nutr. 2002;11(4):314-8.
  Title: Effect of different curcumin dosages on human gall bladder.
  Authors: Rasyid A, Rahman AR , Jaalam K, Lelo A.

• Infection of epithelial cells by the microbial pathogen Helicobacter pylori leads to activation of the transcription factor nuclear factor kappaB(NF-kappaB), the induction of pro-inflammatory cytokine/chemokine genes, and the motogenic response (cell scattering). Curcumin, due to inhibition of NF-kappaB activation and cell scattering, inhibited these responses suggesting that the compound could be considered as a potential therapeutic agent effective against pathogenic processes initiated by H. pylori infection.
  
  Source:Biochem Biophys Res Commun.2004 Apr 16;316(4):1065-72.
  Title: Curcumin blocks NF-kappaB and the motogenic response in Helicobacter pylori-infected epithelial cells.
  Authors: Foryst-Ludwig A, Neumann M, Schneider-Brachert W, Naumann M.

• A review is presented on different categories of compounds that have been studied for the inhibition of the HIV-1 integrase to develop anti-HIV agents. These compounds are: oligonucleotides (double-stranded, triplex, and G-quartet), curcumin analogues, polyhydroxylated aromatic compounds, diketo acids, caffeoyl- and galloyl - based compounds, hydrazides and amides, tetracyclines, and depsides and depsidones. For all these compounds, the important structural features essential for the inhibition of the integrase are pointed out.
  
  Source: Curr Med Chem. 2003 Sep;10(18):1779-94.
  Title: Design and development of integrase inhibitors as anti-HIV agents.
  Authors: Gupta SP, Nagappa AN.
  
  
• Inhibition of the accumulation of protease-resistant prion protein (PrP-res) is a prime strategy in the development of potential transmissible spongiform encephalopathy (TSE) therapeutics. It is shown that curcumin potently inhibits PrP-res accumulation in scrapie agent-infected neuroblastoma cells (50% inhibitory concentration, approximately 10 nM) and partially inhibits the cell-free conversion of PrP to PrP-res. In vivo studies showed that dietary administration of curcumin had no significant effect on the onset of scrapie in hamsters. Nonetheless, other studies have shown that curcumin is nontoxic and can penetrate the brain, properties that give curcumin advantages over inhibitors previously identified as potential prophylactic and/or therapeutic anti-TSE compounds.
  
  Source: J Virol. 2003 May;77(9):5499-502.
  Title: Inhibition of protease-resistant prion protein accumulation in vitro by curcumin.
  Authors: Caughey B, Raymond LD, Raymond GJ, Maxson L, Silveira J, Baron GS.

• An HPLC assay was developed using three methods of plasma sample preparation in order to quantitate curcumin. The assay was developed in an effort to quantify extremely low curcumin plasma concentrations observed in preliminary in vivo studies. The most sensitive assay can reliably detect concentrations down to 2.5 ng/ml. Source: J. Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jan 5;783(1):287-95.
  
  Title: Curcumin in plasma and urine: quantitation by high-performance liquid chromatography
  Authors: Dennis D. Heath , Milagros A. Pruitt, Dean E. Brennerand Cheryl L. Rock

• A large number of studies on curcumin were identified using literature and web sources. These included studies on the antioxidant, anti-inflammatory, antiviral, and antifungal properties of curcuminoids. Studies on the toxicity and anti-inflammatory properties of curcumin have included in vitro, animal, and human studies.
  A phase 1 human trial with 25 subjects using up to 8000 mg of curcumin per day for 3 months found no toxicity from curcumin. Five other human trials using 1125-2500 mg of curcumin per day have also found it to be safe. Curcumin has been demonstrated to be safe in six human trials and has demonstrated anti-inflammatory activity. It may exert its anti-inflammatory activity by inhibition of a number of different molecules that play a role in inflammation.
  
  Source: J Altern Complement Med. 2003 Feb;9(1):161-8.
  Title: Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa).
  Authors: Chainani-Wu N.
  
  
  
• The authors review the medicinal benefits and documented safety of Turmeric (Curcuma longa) which is extensively used as a spice, food preservative and colouring material in India, China and South East Asia and has been used in traditional medicine as a household remedy for various diseases, including biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism and sinusitis.. Clinically, curcumin has already been used to reduce post-operative inflammation . The authors mention that Safety evaluation studies indicate that both turmeric and curcumin are well tolerated at a very high dose without any toxic effects. Therefore both turmeric and curcumin have the potential for the development of modern medicine for the treatment of various diseases.
  
  Source: Current Science, Vol. 87, No. 1, 10 July 2004
  Title: Turmeric and curcumin: Biological actions and medicinal applications
  Authors: Ishita Chattopadhyay, Kaushik Biswas, Uday Bandyopadhyay and Ranajit K. Banerjee
  
  
  
• The most detailed studies using curcumin include anti-inflammatory, antioxidant, anticarcinogenic, antiviral, and antiinfectious activities. In addition, the wound healing and detoxifying properties of curcumin have also received considerable attention. As a result of extensive research on the therapeutic properties of curcumin, some understanding on the cellular, molecular, and biochemical mechanism of action of curcumin is emerging. These findings are summarized in this review.
  
  Source: Crit Rev Food Sci Nutr. 2004;44(2):97-111.
  Title: Biological properties of curcumin-cellular and molecular mechanisms of action.
  Authors: Joe B, Vijaykumar M, Lokesh BR.
  
  
  
• In the present study the antioxidant, anticancer, and antimycobacterial activities of extracts from ginger (Zingiber officinale Roscoe), rosemary (Rosmarinus officinalis L.), and turmeric (Curcuma longa L.) were evaluated. The extracts were obtained using supercritical CO(2) with and without ethanol and/or isopropyl alcohol as cosolvent. The extracts' antioxidant power was assessed using the reaction between beta-carotene and linolenic acid, the antimycobacterial activity against M. tuberculosis was measured by the MABA test, and their anticancer action was tested against nine human cancer ancestries: lung, breast, breast resistant, melanoma, colon, prostate, leukemia, and kidney. The rosemary extracts exhibited the strongest antioxidant and the lowest antimycobacterial activities. Turmeric extracts showed the greatest antimycobacterial activity. Ginger and turmeric extracts showed selective anticancer activities.
  
  Source: J Agric Food Chem. 2003 Apr 23;51(9):2520-5.
  Title: Functional properties of spice extracts obtained via supercritical fluid extraction.
  Authors: Leal PF, Braga ME , Sato DN, Carvalho JE, Marques MO, Meireles MA.
  
  
  
• Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies consumed capsules compatible with curcumin doses between 0.45 and 3.6 g daily for up to 4 months. Levels of curcumin and its metabolites in plasma, urine, and feces were analyzed by high-pressure liquid chromatography and mass spectrometry. Three biomarkers of the potential activity of curcumin were translated from preclinical models and measured in patient blood leukocytes: glutathione S-transferase activity, levels of M(1)G, and PGE(2) production induced ex vivo. A daily oral dose of 3.6 g of curcumin is advocated for Phase II evaluation in the prevention or treatment of cancers outside the gastrointestinal tract, and Levels of curcumin and its metabolites in the urine can be used to assess general compliance.
  
  Source: Clin Cancer Res. 2004 Oct 15;10(20):6847-54.
  Title: Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance.
  Authors: Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM, Pirmohamed M, Gescher AJ, Steward WP.