1. Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer.

Swarnakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV.
J Biol Chem. 2005 Mar 11;280(10):9409-15.
This study is aimed at determining the regulation of MMP-9 and -2 activities in indomethacin-induced acute gastric ulceration and healing. Indomethacin-ulcerated stomach extracts exhibit significant up-regulation of pro-MMP-9 (92 kDa) activity and moderate reduction of MMP-2 activity, which strongly correlate with indomethacin dose and severity of ulcer. The anti-inflammatory and antioxidant properties of curcumin, an active component of turmeric, suggest that curcumin may exert antiulcer activity through scavenging reactive oxygen species, by regulating MMP activity, or both. To test these possibilities, the effect of curcumin in indomethacin-induced gastric ulcer is examined by biochemical and histological methods. The results show that curcumin exhibits potent antiulcer activity in acute ulcer in rat model by preventing glutathione depletion, lipid peroxidation, and protein oxidation. We conclude that antiulcer activity of curcumin is primarily attributed to MMP-9 inhibition, one of the major path-ways of ulcer healing.

2. Curcumin for malaria therapy.

Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN.
Biochem Biophys Res Commun. 2005 Jan 14;326(2):472-4.
Malaria remains a major global health concern. New, inexpensive, and effective antimalarial agents are urgently needed. Here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant Plasmodium falciparum growth in culture in a dose dependent manner with an IC(50) of approximately 5 microM. Additionally, oral administration of curcumin to mice infected with malaria parasite (Plasmodium berghei) reduces blood parasitemia by 80-90% and enhances their survival significantly. Thus, curcumin may represent a novel treatment for malarial infection.

1. Inhibition of NFkappaB activation with curcumin attenuates plasma inflammatory cytokines surge and cardiomyocytic apoptosis following cardiac ischemia/reperfusion.

Yeh CH, Chen TP, Wu YC, Lin YM, Jing Lin P.
J Surg Res. 2005 May 1;125(1):109-16.

BACKGROUND: Following cardiopulmonary bypass (CPB) and cardiac global ischemia and reperfusion, pro-inflammatory cytokines are activated and cause cardiomyocytic injury. Nuclear factor (NF)-kappaB is involved in regulating inflammatory signal transduction. Curcumin inhibits NF-kappaB activation and blocks the inflammatory responses. We studied whether curcumin could decrease myocardial ischemia/reperfusion injury with cardioplegia during CPB and attenuate the appearance of apoptosis of cardiomyocytes. CONCLUSIONS: Curcumin, an inhibitor of NF-kappaB, ameliorated the surge of pro-inflammatory cytokines during CPB and decreased the occurrence of cardiomyocytic apoptosis after global cardiac ischemia/reperfusion injury.

Diabetes

1. Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice.

Nishiyama T, Mae T, Kishida H, Tuskagawa M, Mimaki Y, Kuroda M, Sashida Y, Takahasi K, Kawada T, Nakagawa K, Kitahara M. J Agric Food Chem. 2005 Feb 23; 53(4): 959-63.
In this study, we investigated the effects of three turmeric extracts on blood glucose levels in type 2 diabetic KK-A(y) mice (6 weeks old, n = 5/group). These turmeric extracts were obtained by ethanol extraction (E-ext) to yield both curcuminoids and sesquiterpenoids, hexane extraction (H-ext) to yield sesquiterpenoids, and ethanol extraction from hexane-extraction residue (HE-ext) to yield curcuminoids. These results indicate that both curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via PPAR-gamma activation as one of the mechanisms, and suggest that E-ext including curcuminoids and sesquiterpenoids has the additive or synergistic effects of both components.

2. Curcumin and turmeric delay streptozotocin-induced diabetic cataract in rats.

Suryanarayana P, Saraswat M, Mrudula T, Krishna TP, Krishnaswamy K, Reddy GB.
Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2092-9.
PURPOSE: The purpose of this study was to investigate the effect of curcumin and its source, turmeric, on streptozotocin-induced diabetic cataract in rats. CONCLUSIONS: The results indicate that turmeric and curcumin are effective against the development of diabetic cataract in rats. Further, these results imply that ingredients in the study's dietary sources, such as turmeric, may be explored for anticataractogenic agents that prevent or delay the development of cataract.

3. Hypoglycemic effects of turmeric (Curcuma longa L. Rhizomes) on genetically diabetic KK-Ay mice.

Kuroda M, Mimaki Y, Nishiyama T, Mae T, Kishida H, Tsukagawa M, Takahashi K, Kawada T, Nakagawa K, Kitahara M.
Biol Pharm Bull. 2005 May;28(5):937-9.
The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In an in vitro evaluation, the extract stimulated human adipocyte differentiation in a dose-dependent manner and showed human peroxisome proliferator-activated receptor (PPAR)-gamma ligand-binding activity in a GAL4-PPAR-gamma chimera assay. The main constituents of the extract were identified as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.

4. Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice.

Nishiyama T, Mae T, Kishida H, Tsukagawa M, Mimaki Y, Kuroda M, Sashida Y, Takahashi K, Kawada T, Nakagawa K, Kitahara M. J Agric Food Chem. 2005 Feb 23;53(4):959-63.
In this study, we investigated the effects of three turmeric extracts on blood glucose levels in type 2 diabetic KK-A(y) mice (6 weeks old, n = 5/group). These results indicate that both curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via PPAR-gamma activation as one of the mechanisms, and suggest that E-ext including curcuminoids and sesquiterpenoids has the additive or synergistic effects of both components.

5. Curcumin attenuates diet-induced hypercholesterolemia in rats.

Arafa HM.
Med Sci Monit. 2005 Jul;11(7):BR228-234. Epub 2005 Jun 29.
The hypolipidemic effect of curcumin was studied in rats that were fed a high-cholesterol diet (HCD). Lipid profile and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed in serum, and anti-oxidant parameters were assessed in liver tissues. Curcumin mixed with a high cholesterol diet decreased serum total cholesterol and LDL-C but increased serum HDL. Curcumin decreased enzyme activities of serum AST and ALT.

6. Relationship between intracellular ROS production and membrane mobility in curcumin- and tetrahydrocurcumin-treated human gingival fibroblasts and human submandibular gland carcinoma cells.

Atsumi T, Fujisawa S, Tonosaki K.
Oral Dis. 2005 Jul;11(4):236-42.
This study investigates the relationship between cell membrane mobility and reactive oxygen species (ROS) production to examine the antioxidant mechanism of curcumin and tetrahydrocurcumin (THC). Curcumin dose-dependently produced ROS, ROS appeared in the region surrounding the cell membrane. Curcumin lowered membrane mobility, which was reversed by the addition of glutathione. THC did not affect ROS production or membrane mobility.

7. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

Rukkumani R, Aruna K, Varma PS, Rajasekaran KN, Menon VP
J Med Food. 2005 Summer;8(2):256-60.
This study tests the effect of curcumin and a curcumin analog on alcohol-induced hyperlipidemia. The levels of cholesterol, triglycerides, phospholipids and free fatty acids were analyzed. Results showed that cholesterol, triglycerides, phospholipids and fatty acid levels were increased by alcohol, which were decreased by curcuminoid treatment.

8. Effect of photo-irradiated curcumin treatment against oxidative stress in streptozotocin-induced diabetic rats.

Mahesh T, Balasubashini MS, Menon VP
J Med Food. 2005 Summer;8(2):251-5.
Oxidative stress is a major proponent in the pathogenesis of diabetes mellitus. This study evaluates the anti-hyperglycemic properties of curcumin in experimental diabetes. Blood glucose levels were elevated in diabetic animals, circulatory lipid peroxidation, vitamin C, vitamin E and enzymic antioxidants were analyzed. Curcumin, when administered for 45 days, decreased blood glucose levels and brought enyzmic activities and lipid peroxidation to normal levels.

9. Effect of curcumin on immune function of mice.

Li X, Liu X.
J Huazhong Univ Sci Technolog Med Sci. 2005;25(2):137-40.
Curcumin effects on mice spleen lymphocyte proliferation and function of phagocytosis of peritoneal macrophage were examined. Curcumin enhances phagocytosis of peritoneal macrophages. Lowdose Curcumin upregulates spleen lymphocyte proliferation, high dose Curcumin suppresses spleen lymphocyte proliferation. Curcumin can regulate immune function of mice in dose-dependent manner.

10. Modulation of alpha-crystallin chaperone activity in diabetic rat lens by curcumin

Kumar PA, Suryanarayana P, Reddy PY, Reddy GB
Mol Vis. 2005 Jul 26;11:561-8.
Curcumin was investigated to test whether or not it can manipulate the chaperone-like activity of alpha-crystallin in diabetic rat lens. Rats were administered streptozotocin to induce hyperglycemia, then treated with Curcumin. Hyperglycemia-induced cataract progression was monitored. Chaperone activity, hydrophobicity and secondary and tertiary structure of alphaH- and alphaL-crystalline were assessed. There was a decrease in chaperone-like activity in alphaH- and alphaL-crystallins. This was associated with reduced hydrophobicity. Dietary levels of curcumin prevented chaperone-like activity loss of alpha-crystallin.

1. Water-soluble antioxidants improve the antioxidant and anticancer activity of low concentrations of curcumin in human leukemia cells.

Chen J, Wanming D, Zhang D, Liu Q, Kang J.
Pharmazie. 2005 Jan;60(1):57-61.
In the present study, concentration-dependent regulation of Cur on cell proliferation, viability and ROS generation, and effect of water-soluble antioxidants ascorbic acid (ASA), N-acetyl-cysteine (NAC) and reduced glutathione (GSH) on the antioxidant and anticancer activity of Cur were investigated in human myeloid leukemia cells (HL-60 cells). We found that although Cur concentration- and time-dependently decreased the proliferation and viability of cells, its effect on ROS generation (as indicated by the level of malondialdehyde, MDA) varied with its concentrations. I.e., low concentrations of Cur diminished the ROS generation, while high Cur promoted it. Considering that the extra accumulation of ROS is harmful to normal cells, the data presented here indicate that instead of using high doses, combining low doses of Cur with water-soluble antioxidants is a better strategy for us to improve the anticancer activity of Cur.

2. Antioxidant and antiproliferative activity of curcumin semicarbazone.

Dutta S, Padhye S, Priaydarsini KI, Newton C.
Bioorg Med Chem Lett. 2005 Jun 2;15(11):2738-44.
A new semicarbazone derivative of curcumin (CRSC) was synthesized and examined for its antioxidant, antiproliferative, and antiradical activity and compared with those of curcumin (CR). The antioxidant activity was tested by their ability to inhibit radiation induced lipid peroxidation in rat liver microsomes. The antiproliferative activity was tested by studying the in vitro activity of CRSC against estrogen dependant breast cancer cell line MCF-7. The results suggest that the probable site of attack for CRSC is both the phenolic OH and the imine carbonyl position. CRSC shows efficient antioxidant and antiproliferative activity although its antiradical activity is less than that of CR.

3. Anti-oxidant activities of curcumin and related enones.

Weber WM, Hunsaker LA, Abcouwer SF, Deck LM, Vander Jagt DL.
Bioorg Med Chem. 2005 Jun 1;13(11):3811-20.
The natural product curcumin (diferuloylmethane, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), obtained from the spice turmeric, exhibits numerous biological activities including anti-cancer, anti-inflammatory, and anti-angiogenesis activities.. There are conflicting reports concerning the structural/electronic basis of the anti-oxidant activity of curcumin. Curcumin is a symmetrical diphenolic dienone. A series of enone analogues of curcumin were synthesized that included: (1) curcumin analogues that retained the 7-carbon spacer between the aryl rings; (2) curcumin analogues with a 5-carbon spacer; and (3) curcumin analogues with a 3-carbon spacer (chalcones). These series included members that retained or were devoid of phenolic groups. Anti-oxidant activities were determined by the TRAP assay and the FRAP assay. Most of the analogues with anti-oxidant activity retained the phenolic ring substituents similar to curcumin. However, a number of analogues devoid of phenolic substituents were also active; these non-phenolic analogues are capable of forming stable tertiary carbon-centered radicals.

4. Metal-induced oxidative damage in cultured hepatocytes and hepatic lysosomal fraction: beneficial effect of a curcumin/absinthium compound.

Barreto R, Kawakita S, Tsuchiya J, Minelli E, Pavasuthipaisit K, Helmy A, Marotta F
Chin J Dig Dis. 2005; 6(1): 31-6.
OBJECTIVE: Metals undergo redox cycling and there is increasing evidence of free radical generation and oxidative injury in the pathogenesis of liver injury and fibrosis in metal storage diseases. The aim of the present study was to test a natural hepatoprotective compound in metal-induced liver injury. CONCLUSION: These data support the potential clinical application of curcumin-containing compounds.

5. Curcumin ameliorates oxidative stress during nicotine-induced lung toxicity in Wistar rats.

Kalpana C, Menon VP.
Ital J Biochem. 2004 Jul;53(2):82-6.
Nicotine, a major toxic component of cigarette smoke has been identified as a major risk factor for lung related diseases. In the present study, we evaluated the protective effects of curcumin on lipid peroxidation and antioxidants status in bronchoalveolar lavage fluid (BALF) and bronchoalveolar lavage (BAL) of nicotine treated Wistar rats. The results of the present study suggest that curcumin exert its protective effect against nicotine-induced lung toxicity by modulating the biochemical marker enzymes, lipid peroxidation and augmenting antioxidant defense system.

1. Antiangiogenic agents: studies on fumagillin and curcumin analogs.

Furness MS, Robinson TP, Ehlers T, Hubbard RB 4th, Arbiser JL, Goldsmith DJ, Bowen JP.
Curr Pharm Des. 2005;11(3):357-73.
Abnormal cellular behavior are specific to each type of cancer. One common denominator for all types of cancer is the requirement of a suitable blood supply. Tumor vasculature has emerged as a potential target for therapeutic intervention. Diffusion from nearby capillaries can supply adequate nutrition for tumors less than 2 mm in size, but for continued growth the tumors must develop their own blood supply. The goal of antiangiogenic therapy is to interfere with these mechanisms and prevent tumor cells from developing a viable blood supply. Fumagillin is a naturally occurring antifungal agent. Curcumin is a natural product isolated from the spice turmeric. Both compounds have been shown to have antiangiogenic properties in vitro and in vivo. This paper describes efforts to design and prepare fumagillin and curcumin analogs and evaluate their corresponding antiangiogenic activities.

2. Antimicrobial activity of Curcuma zedoaria and Curcuma malabarica tubers.

Wilson B, Abraham G, Manju VS, Mathew M, Vimala B, Sundaresan S, Nambisan B.
J Ethnopharmacol. 2005 May 13; 99(1): 147-51.
The antimicrobial activity of extracts of Curcuma zedoaria and Curcuma malabarica tubers was tested against six bacterial and two fungal strains using the agar well diffusion and broth dilution methods. Petroleum ether, hexane, chloroform, acetone and ethanol extracts exhibited antibacterial as well as antifungal activity. Acetone and hexane extracts of both tubers showed comparable antimicrobial activity as indicated by minimum inhibitory concentration (MIC) values, but other extracts of Curcuma malabarica showed significantly lower activity than those of Curcuma zedoaria. The MIC values for different strains and extracts ranged from 0.01 to 0.15 mg/ml in Curcuma zedoaria and from 0.01 to 0.94 mg/ml in Curcuma malabarica. Staphylococcus aureus (Gram positive) was inhibited by Curcuma malabarica but not by Curcuma zedoaria. This study is the first report of the antimicrobial properties of Curcuma malabarica. The findings also support the use of Curcuma zedoaria tubers in traditional medicine for the treatment of bacterial and fungal infections.

1. Active site binding modes of curcumin in HIV-1 protease and integrase.

Vajragupta O, Boonchoong P, Morris GM, Olson AJ.
Bioorg Med Chem Lett. 2005 Jul 15; 15(14): 3364-8.
The interaction of curcumin with HIV-1 integrase (IN) and protease (PR) were studied using structure models. Curcumin binds preferentially in similar ways to the active sites of both IN and PR. The binding site is formed by residues Asp64, His67, Thr66, Glu92, Thr93, Asp116, Ser119, Asn120 and Lys159 for IN. In the PR docking, curcumin structure fitted well to the active site, interacting with residues Asp25, Asp29, Asp30, Gly27’, Asp29’ and Asp30’. The symmetrical structure for curcumin seems to play an important role for binding to the PR protein.

2. Curcumin Blocks HIV Protease Inhibitor Ritonavir-Induced Vascular Dysfunction in Porcine Coronary Arteries.

Chai H, Yan S, Lin P, Lumsden AB, Yao Q, Chen C.
J Am Coll Surg. 2005 Jun;200(6):820-30.
BACKGROUND: HIV protease inhibitor ritonavir (RTV) is associated with many cardiovascular complications and causes vascular dysfunction through oxidative stress. In the present study, we determined the effects of RTV and curcumin (a pigment derived from turmeric) on porcine coronary arteries. CONCLUSIONS: HIV protease inhibitor RTV impairs vasomotor functions, reduces eNOS expression and nitric oxide release, and increases oxidative stress in porcine coronary arteries. Curcumin effectively blocks these detrimental effects of RTV.

3. Herbal medicines for treating HIV infection and AIDS.

Liu J, Manheimer E, Yang M.
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003937.
The beneficial effects of herbal medicines in patients with HIV infection and AIDS were assessed. 499 individuals in nine randomized placebo-controlled trials participated in the study. There were eight herbal medicines tested. A compound of Chinese herbs (IGM-1) was significantly better than placebo in improving health-related quality of life in 30 symptomatic HIV-infected patients, without affecting overall health perception, symptom severity and CD4 count. A combined treatment of a Chinese herbal compound SH and antiretroviral agents had an increased antiviral benefit when compared with the antiretroviral alone. The herb Qiankunning did not affect HIV-1 RNA levels, curcumin was ineffective in reducing viral load or improving CD4 counts, and capsaicin was ineffective in relieving pain.

4. Effect of artemisinin/artesunate as inhibitors of hepatitis B virus production in an "in vitro" replicative system.

MA, Castano B, Macias RI, Briz O, Marin JJ
Antiviral Res. 2005 Aug 22.
Artemisinin and other compounds from Chinese medicine were examined for their antiviral effects against hepatitis B virus (HBV). Daidzein, daidzin, isonardosinon, nardofuran, nardosinon, tetrahydronardosinon and quercetin had no effect on viral production. Berberine and tannic acid markedly reduced viral production but had toxic effects. Curcumin, baicalein, baicalin, bufalin, diallyl disulphide, glycyrrhizic acid and puerarin moderately reduced the virus. Artemisinin and artesunate had a strong inhibition of viral production with no danger to cell viability.

5. Curcumin for malaria therapy.

Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN.
Biochem Biophys Res Commun. 2005 Jan 14;326(2):472-4.
Malaria remains a major global health concern. New, inexpensive, and effective antimalarial agents are urgently needed. Here we show that curcumin, a polyphenolic organic molecule derived from turmeric, inhibits chloroquine-resistant Plasmodium falciparum growth in culture in a dose dependent manner with an IC(50) of approximately 5 microM. Additionally, oral administration of curcumin to mice infected with malaria parasite (Plasmodium berghei) reduces blood parasitemia by 80-90% and enhances their survival significantly. Thus, curcumin may represent a novel treatment for malarial infection.

1. Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammatory agents.

Selvam C, Jachak SM, Thilagavathi R, Chakraborti AK
Bioorg Med Chem Lett. 2005 Apr 1;15(7):1793-7.
Curcuminoids were isolated from Curcuma longa and their pyrazole and isoxazole analogues were synthesized and evaluated for antioxidant, COX-1/COX-2 inhibitory and anti-inflammatory activities. The designed analogues significantly enhance COX-2/COX-1 selectivity and possess significant anti-inflammatory activity in carrageenan induced rat paw edema assay. Pyrazole, isoxazole analogues of curcumin (4 and 7) exhibited higher antioxidant activity than trolox. Molecular docking study revealed the binding orientations of curcumin analogues in the active sites of COX and thereby helps to design novel potent inhibitors.

2. Stability-indicating HPTLC determination of curcumin in bulk drug and pharmaceutical formulations.

Ansari MJ, Ahmad S, Kohli K, Ali J, Khar RK
J Pharm Biomed Anal. 2005 Sep 1;39(1-2):132-8.
A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of curcumin both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (9.25:0.75v/v). This system was found to give compact spots for curcumin (R(f) value of 0.48+/-0.02). Densitometric analysis of curcumin was carried out in the absorbance mode at 430nm. The linear regression analysis data for the calibration plots showed good linear relationship with r=0.996 and 0.994 with respect to peak height and peak area, respectively, in the concentration range 50-300ng per spot. The mean value+/-S.D. of slope and intercept were 1.08+/-0.01, 51.93+/-0.54 and 8.39+/-0.21, 311.55+/-3.23 with respect to peak height and area, respectively. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 8 and 25ng per spot, respectively. Curcumin was subjected to acid and alkali hydrolysis, oxidation and photodegradation. The drug undergoes degradation under acidic, basic, light and oxidation conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and photo oxidation. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. As the method could effectively separate the drug from its degradation product, it can be employed as a stability-indicating one.

3. Synthesis and biological evaluation of aromatic enones related to curcumin.

Robinson TP, Hubbard RB 4th, Ehlers TJ, Arbiser JL, Goldsmith DJ, Bowen JP.
Bioorg Med Chem. 2005 Jun 2;13(12):4007-13.
Curcumin has been specifically shown to be an effective inhibitor of angiogenesis both in vitro and in vivo. Using curcumin as a lead compound for anti-angiogenic analog design, a series of structurally related compounds utilizing a substituted chalcone backbone have been synthesized and tested via an established SVR cell proliferation assay. The results have yielded a wide range of compounds that equal or exceed curcumin's ability to inhibit endothelial cell growth in vitro. Due to both their commercial availability and their fairly straightforward synthetic preparation, these low molecular weight compounds are attractive leads for developing future angiogenic inhibitors.

4. Design, synthesis, biological evaluation and molecular docking of curcumin analogues as antioxidant, cyclooxygenase inhibitory and anti-inflammatory agents.

Selvam C, Jachak SM, Thilagavathi R, Chakraborti AK
Bioorg Med Chem Lett. 2005 Apr 1;15(7):1793-7.
Curcuminoids were isolated from Curcuma longa and their pyrazole and isoxazole analogues were synthesized and evaluated for antioxidant, COX-1/COX-2 inhibitory and anti-inflammatory activities. The designed analogues significantly enhance COX-2/COX-1 selectivity and possess significant anti-inflammatory activity in carrageenan induced rat paw edema assay. Pyrazole, isoxazole analogues of curcumin (4 and 7) exhibited higher antioxidant activity than trolox. Molecular docking study revealed the binding orientations of curcumin analogues in the active sites of COX and thereby helps to design novel potent inhibitors.

5. Pharmacological basis for the use of turmeric in gastrointestinal and respiratory disorders.

Gilani AH, Shah AJ, Ghayur MN, Majeed K.
Life Sci. 2005 May 13;76(26):3089-105.
This study was carried out to provide scientific basis for the medicinal use of turmeric (Curcuma longa) in gastrointestinal and respiratory disorders.. When used for comparison, both curcumin and verapamil caused similar inhibitory effects in all smooth muscle preparations with relatively more effect against K(+)-induced contractions and that both were devoid of any vasoconstrictor effect and curcumin had no effect on atria. These data suggest that the inhibitory effects of Cl.Cr are mediated primarily through calcium channel blockade, though additional mechanism cannot be ruled out and this study forms the basis for the traditional use of turmeric in hyperactive states of the gut and airways. Furthermore, curcumin, the main active principle, does not share all effects of turmeric.

6. The effects of curcumin on depressive-like behaviors in mice.

Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ.
Eur J Pharmacol. 2005 Jul 25;518(1):40-6.
The effects of curcumin on depressive-like behaviors in mice were analyzed. Two animal models of depression were used. Curcumin doses of 5 and 10 mg/kg (p.o.) reduced the duration of immobility in tail suspension and forced swimming tests. These doses, however, did not affect locomotor activity. Curcumin increased serotonin and noradrenaline levels at 10 mg/kg in the frontal cortex and hippocampus. Curcumin increased dopamine levels in the frontal cortex and the striatum. Curcumin also inhibted monamine oxidase activity in the mouse brain.

7. Comparative effects of curcumin and an analogue of curcumin in carbon tetrachloride-induced hepatotoxicity in rats.

Kamalakkannan N, Rukkumani R, Varma PS, Viswanathan P, Rajasekharan KN, Menon VP.
Basic Clin Pharmacol Toxicol. 2005 Jul;97(1):15-21.
The effect of curcumin and its analogue were evaluated on carbon tetrachloride-induced hepatotoxicity in rats. Carbon tetrachloride increased levels of marker enzymes (aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase) when administered for three months. Plasma thiobarbituric acid reactive substances and lipid hydroperoxides also significantly increased. Oral adminstration of curcumin and BDMC-A to rats with hepatotoxicity for three months decreased the levels of marker enzymes, plasma TBARS and hydroperoxides and increased levels of plasma and tissue antioxidants.

8. Effects of dietary curcumin or N-acetylcysteine on NF-kappaB activity and contractile performance in ambulatory and unloaded murine soleus.

Farid M, Reid MB, Li YP, Gerken E, Durham WJ
Nutr Metab (Lond). 2005 Aug 26;2(1):20.
Skeletal muscle unloading leads to atrophy and loss of contractile function. This is thought to be mediated by nuclear factor-kappa B (NF-kappaB). Curcumin and N-acetylcysteine (NAC) can inhibit activation of NF-kappaB. This study tests the effect of Curcumin and NAC on skeletal muscle unloading. Results concluded that Curcumin and NAC ingested through diet did not prevent dysfunction of skeletal muscle and atrophy.

9. Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats.

Kalpana C, Rajasekharan KN, Menon VP.
J Med Food. 2005 Summer;8(2):246-50.
The effects of a Curcumin analog and Curcumin on biochemical marker enzymes and lipid profiles on nicotine-induced toxicity in Wistar rats were measured. Biochemical marker enzymes such as aspartate transaminase, alanine transaminase, alkaline phosphatase and lactate dehydrogenase and plasma lipid profiles were used to measure their anti-hyperlipidemic effects. Curcumin and curcumin analog administration significantly reduced marker enzyme activity and reduced plasma lipid levels in the nicotine-treated rats.

10. Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-D: -aspartate-induced intracellular Ca(2+) increase.

Matteucci A, Frank C, Domenici MR, Balduzzi M, Paradisi S, Carnovale-Scalzo G, Scorcia G, Malchiodi-Albedi F.
Exp Brain Res. 2005 Aug 3;:1-8.
Curcumin was tested in rat retinal cultures as a protecting agent against excitotoxicity. Curcumin reduced NMDA-mediated excitotoxic cell damage, this was associated decrease of NMDA receptor-mediated Ca(2+) rise and reduction in the phosphorylated NR-1 subunit of the NMDA receptor.

11. Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits.

Wang Q, Sun AY, Simonyi A, Jensen MD, Shelat PB, Rottinghaus GE, Macdonald RS, Miller DK, Lubahn DE, Weisman GA, Sun GY J Neurosci Res. 2005 Aug 1.
Neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury is caused in part by increased oxidative stress. This study focused on the mechanisms underlying the neuroprotective effects of curcumin. Cerebral ischemia was induced in gerbils, histochemical analysis showed extensive neuronal death and an increase in astrocytes and microglial cells in the hippocampal CA1 area 4 days after I/R. Lipid peroxidation and cytochrome c also increased, activating caspase-3 and apoptosis. Administration of Curcumin decreased ischemia-induced neuronal death and glial activation. It also decreased lipid peroxidation and apoptotic indices. Bioavailability study showed that Curcumin was present in the brain 1 hour after treatment when administered intra-peritoneally.

12. Curcumin has a palliative action on gentamicin-induced nephrotoxicity in rats.

Ali BH, Al-Wabel N, Mahmoud O, Mousa HM, Hashad M
Fundam Clin Pharmacol. 2005 Aug;19(4):473-7.
Gentamicin (GM) nephrotoxicity pathogenesis is due to the generation of free radicals in the kidney cortex. Curcumin was tested for its protective and pallitive effect on GM nephroxicity. Necrosis lessened when GM was given simultaneously with curcumin, the concentration of GM in the renal cortex of rats given both GM and curcumin was significantly lower than that found in rats treated with GM alone. This indicates that curcumin may be a powerful nephroprotectant agent.

Chan WH, Wu HJ, Hsuuw YD.
Ann N Y Acad Sci. 2005 May;1042:372-378.
Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Elevated MG levels in diabetes patients are believed to contribute to diabetic complications. MG is cytotoxic through induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties. In the present study, we investigated the effect of curcumin on MG-induced apoptotic events in human hepatoma G2 cells. We report that curcumin prevented MG-induced cell death and apoptotic biochemical changes such as mitochondrial release of cytochrome c, caspase-3 activation, and cleavage of PARP (poly [ADP-ribose] polymerase). Using the cell permeable dye 2',7'-dichlorofluorescein diacetate (DCF-DA) as an indicator of reactive oxygen species (ROS) generation, we found that curcumin abolished MG-stimulated intracellular oxidative stress. The results demonstrate that curcumin significantly attenuates MG-induced ROS formation, and suggest that ROS triggers cytochrome c release, caspase activation, and subsequent apoptotic biochemical changes.

2. Effect of curcumin on expression of human low density lipoprotein receptors in Xenopus Laevis oocytes

Fan CL, Wo XD, Luo Y
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2005 May;25(5):432-5.
OBJECTIVE: To investigate the molecular mechanism of curcumin in reducing blood lipids by establishing gene expression system of human low density lipoprotein receptors (LDL-R) in Xenopus Laevis oocytes (XLO). RESULTS: The human LDL-R gene could be expressed on XLO, which could be significantly enhanced by curcumin in a dose-dependent manner. Conclusion One of the paths of curcumin in reducing blood lipids and anti-atherosclerosis was improving LDL-R gene expression and increasing the LDL-cholesterol absorption of cells.

3. Suppressive effects of dietary curcumin on the increased activity of renal ornithine decarboxylase in mice treated with a renal carcinogen, ferric nitrilotriacetate.

Okazaki Y, Iqbal M, Okada S.
Biochim Biophys Acta. 2005 Jun 10;1740(3):357-66. Epub 2004 Sep 25.
Dietary supplementation of curcumin enhances the activities of antioxidant and phase II metabolizing enzymes in mice (M. Iqbal, S.D. Sharma, Y. Okazaki, M. Fujisawa, S. Okada, 2003) and inhibits ferric nitrilotriacetate (Fe-NTA) induced oxidative injury of lipids and DNA in vitro (M. Iqbal, Y. Okazaki, S. Okada, 2003). Fe-NTA is a known renal carcinogen that generates ROS in vivo. In this study, Fe-NTA was administered intraperitoneally to mice. Curcumin was tested for its ability to inhibit oxidative stress. Curcumin normalized the carcinogenic activities of Fe-NTA. Mice pretreated with curcumin prevented oxidative damage in kidney biomolecules and tissue were protected as was observed through histopathology.

4. Oral flavonoids delay recovery from experimental autoimmune encephalomyelitis in SJL mice.

Verbeek R, van Tol EA, van Noort JM
Biochem Pharmacol. 2005 Jul 15; 70(2): 220-8.
The effects of oral flavonoids and curcumin on autoimmune T cell reactivity in mice and on the course of experimental autoimmune encephalomyelitis (EAE) were examined. EAE is a model for multiple sclerosis. Continuous oral administration of flavonoids significantly affected antigen-specific proliferation and IFN-gamma production by lymph node-derived T cells following immunization with an EAE-inducing peptide. In passive EAE, flavonoids led to delayed recovery of clinical symptoms. In active EAE, the effects were less significant, but hesperitin delayed recovery. Curcumin taken orally had beneficial effects. It was concluded that oral flavonoids suppress recovery from acute inflammatory damage.

5. Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats.

Pari L, Amali DR
J Pharm Pharm Sci. 2005 Apr 30;8(1): 115-23.
PURPOSE: Tetrahydrocurcumin (THC) is an antioxidative substance, which is derived from curcumin, the component of turmeric. In the present investigation, the effect of THC and curcumin against chloroquine (CQ) induced hepatotoxicity were studied in female Wistar rats. The biochemical observation was supplemented by histopathological examination of liver section. The results of the study reveal that THC shows more pronounced protective effect than curcumin against CQ induced toxicity.

6. Comparative effects of curcumin and an analogue of curcumin in carbon tetrachloride-induced hepatotoxicity in rats.

Kamalakkannan N, Rukkumani R, Varma PS, Viswanathan P, Rajasekharan KN, Menon VP
Basic Clin Pharmacol Toxicol. 2005 Jul; 97(1): 15-21.
The effect of curcumin and its analogue were evaluated on carbon tetrachloride-induced hepatotoxicity in rats. Carbon tetrachloride increased levels of marker enzymes (aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase) when administered for three months. Plasma thiobarbituric acid reactive substances and lipid hydroperoxides also significantly increased. Oral adminstration of curcumin and BDMC-A to rats with hepatotoxicity for three months decreased the levels of marker enzymes, plasma TBARS and hydroperoxides and increased levels of plasma and tissue antioxidants.

7. Preventive and therapeutic effects of NF-kappaB inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid.

Jian YT, Mai GF, Wang JD, Zhang YL, Luo RC, Fang YX.
World J Gastroenterol. 2005 Mar 28; 11(12): 1747-52.
AIM: To ascertain the molecule mechanism of nuclear factor-kappaB (NF-kappaB) inhibitor curcumin preventive and therapeutic effects in rats' colitis induced by trinitrobenzene sulfonic acid (TNBS). CONCLUSION: This study shows that NF-kappaB inhibitor curcumin could prevent and improve experimental colitis in murine model with inflammatory bowel disease (IBD). The findings suggest that NF-kappaB inhibitor curcumin could be a potential target for the patients with IBD.

8. Apoptosis and age-dependant induction of nuclear and mitochondrial etheno-DNA adducts in Long-Evans Cinnamon (LEC) rats: enhanced DNA damage by dietary curcumin upon copper accumulation.

Nair J, Strand S, Frank N, Knauft J, Wesch H, Galle PR, Bartsch H.
Carcinogenesis. 2005 Jul; 26(7): 1307-15.
In the rat model for human Wilson’s disease, chronic hepatitis and liver tumors develop in the rats due to accumulation of copper and induced oxidative stress. Curcumin failed to prevent liver tumors in LEC rats. Curcumin also had in vitro DNA damaging potential when presented with copper ions.

9. Detection and quantitation of curcumin in mouse lung cell cultures by matrix-assisted laser desorption ionization time of flight mass spectrometry.

May LA, Tourkina E, Hoffman SR, Dix TA
Anal Biochem. 2005 Feb 1; 337(1): 62-9.
A method to detect and quantify curcumin and two curcuminoid metabolites in biological matrices, including mouse serum and mouse lung cell cultures, was developed. Standard curves between 0.04 and 10.00 nmol curcumin were prepared in serum, giving correlation coefficients of 0.94-0.99. Alcoholic extraction, concentration, and addition of dilute hydrochloric acid to stabilize the curcumin were essential to the reproducibility of the protocol. Untreated and curcumin-treated mouse lung fibrotic and nonfibrotic cell cultures were analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry utilizing this method. Curcumin uptake was calculated to be 7.0-11.6% for the saline-treated cells and 7.4-11.9% for the bleomycin-treated cultures. Curcumin was not detected in untreated cells. Two additional peaks (m/z=399 and 429) were observed in the curcumin-treated cells. These may be curcumin-derived products resulting from HCl treatment of the tissue samples.

10. Effects of dietary quillaja saponin and curcumin on the performance and immune status of weaned piglets.

Ilsley SE, Miller HM, Kamel C
J Anim Sci. 2005 Jan; 83(1): 82-8.
The objective of this study was to determine whether dietary quillaja saponin and curcumin (extract of turmeric) can modify piglet immune status and performance immediately after weaning. Saponin supplementation during the postweaning period seemed to potentiate an immune response in the weaned piglet but had a detrimental effect on the utilization of feed. Dietary curcumin had no influence on any measured aspect of pig performance or immune status.

11. Antiatherosclerotic effects of dietary supplementations of garlic and turmeric: Restoration of endothelial function in rats.

Zahid Ashraf M, Hussain ME, Fahim M.
Life Sci. 2005 Jul 8; 77(8): 837-57.
Diet supplements such as garlic and turmeric were examined for their atheroscleroprotective potential. This was examined by measuring serum lipid profile and by changes in cardiovascular parameters such as heart rate. This study also aimed to explain the restoration of endothelial function and role of factors from the endothelium, such as nitric oxide (NO) and cycloxygenase derived contracting factors. Animals on garlic and turmeric supplemented diets had a restoration of arterial blood pressure, enhanced vasorelaxant response to adenosine, acetylcholine, and isoproterenol. The contractile effect of 5-hyderoxytrptamine was significantly attenuated. Garlic and turmeric are vasorelexants and can reduce the atherogenic properties of cholesterol.

12. Application of capillary zone electrophoresis in the separation and determination of the curcuminoids in urine.

Yuan K, Weng Q, Zhang H, Xiang J, Xu G.
J Pharm Biomed Anal. 2005 Jun 1; 38(1): 133-8.
The major components of the plant curcuma longa are the curcuminoids that include curcumin, demethoxycurcumin and bisdemethoxycurcumin. It has been reported the curcuminoids have some important activities. A new CZE method with diode array detection has been developed for the separation and determination of the curcumin, demethoxycurcumin and bisdemethoxycurcumin. Three curcuminoids could be readily separated within 7min with a 15mM sodium tetraborate buffer containing 10% methanol (v/v) at pH 10.8, 25kV and 30 degrees C. The method has been validated and shows good performance with respect to selectivity, reproducibility, linearity, limits of detection and recovery. The proposed method was successfully applied to determine the curcuminoids in urine.

13. Inhibition of multidrug resistance proteins MRP1 and MRP2 by a series of alpha, beta-unsaturated carbonyl compounds.

Wortelboer HM, Usta M, van Zanden JJ, van Bladeren PJ, Rietjens IM, Cnubben NH.
Biochem Pharmacol. 2005 Jun 15;69(12):1879-90.
The interactions of a series of alpha, beta-unsaturated carbonyl compounds with multidrug resistance proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2) were studied. This was used to study the interaction between glutathione metabolism of and MRP inhibition of thiol reactive compounds. Curcumin inhibited MRP1 transport only in the vesicle model pointing at inhibition by the parent compound. The glutathione conjugates of curcumin also inhibit MRP1 mediated transport, but to a much lesser extent than the parent compound curcumin. In the cellular model system, it was demonstrated that glutathione conjugation of curcumin leads to inactivation of its inhibitory potential. Demethoxycurcumin and bisdemethoxycurcumin inhibited MRP1 in both the vesicle and cellular model pointing at inhibitory potency of at least the parent compound and possibly their metabolites. For MRP2, inhibition was much less in both model systems, with the three curcuminoids being the most effective.

14. Resveratrol and curcumin reduce the respiratory burst of Chlamydia-primed THP-1 cells.

Deby-Dupont G, Mouithys-Mickalad A, Serteyn D, Lamy M, Deby C
Biochem Biophys Res Commun. 2005 Jul 22;333(1):21-7.
The intracellular bacterium Chlamydia pneumoniae is ivolved in the inflammation process of atherosclerosis. We previously demonstrated that C. pneumonia infected monocytes (THP-1 cells) responded to stimulation by an increased respiratory burst linked to an increased NADPH oxidase (NOX) activity. We now tested agents acting on the assembly of the NOX subunits or on protein kinase C, a trigger of NOX activity. Apocynin, resveratrol, rutin, quercetin, curcumin, and tocopherols were tested. The cells were pre-incubated with chlamydia and the agent for 19 h, and then stimulated with phorbol myristate acetate. The NOX activity was monitored by measuring the hydrogen peroxide production. Resveratrol and curcumin (10(-4)-10(-6) M) were better inhibitors than apocynin. alpha-Tocopherol was inactive, and gamma-tocopherol inhibitor at 10(-4) M only. Quercetin was inactive, and rutin a moderate but significant inhibitor. The inhibition by resveratrol was increased by 10(-6) M rutin or quercetin. Resveratrol and curcumin thus appeared to be interesting for atherosclerosis treatment.

15. Chemopreventive and therapeutic effects of curcumin.