Hey: pretty much every antioxidant In know has prooxidant effects under certain laboratory conditions. Does that mean we should stop taking them all? The first abstract you pasted above is in vitro in strange types of cells -- HL-60 cells and HSG cells. The second study talks about enzyme modification and how a pro oxidant effect can actually
prevent cancer. The third abstract you pasted merely suggests "that polyphenolics containing a phenol ring are generally more prooxidant than polyphenolics containing a catechol ring."
I don't know if this is nearly as compelling as much of the in vivo data from below (this are just studies from Jan-Sept 2005!!!) If you want to see ALL of the curcumin research see this:
http://www.curcumino...om/research.htm 1. Antiinflammatory/Anticancer
Antitumor/Anticancer/Antimutagenic
1. The inhibitory effect of curcumin on the growth of human colon cancer cells (HT29, WiDr) in vitro
Kim, KH, Park HY, Nam JH, Park JE, Kim JY, Park MI, Chung KO, Park KY, Koo JY.
Korean J Gastroenterol. 2005 Apr; 45(4): 277-84.
BACKGROUND/AIMS: The effects of curcumin on the growth of human colon cancer cell lines, HT-29 and WiDr cells were examined and the effects of 5-fluorouracil (5-FU) were also studied. CONCLUSIONS: Curcumin significantly inhibited the growth of HT-29 and WiDr cells in a dose-dependent, reversible fashion.
2. The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae induced NF-kappaB signaling, release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection.
Wesser S, Muenzner P, Meyer TF, Naumann M.
Biol Chem. 2005 May; 386(5): 481-90.
Induction of tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and IL-8 are proinflammatory cytokines that can be induced by Ngo. This study determined that nuclear factor kappaB (NFkappaB) is a key molecule involved in cytokine release. Curcumin inhibited IKKalpha, IKKbeta and NIK, showing that it has the potential to block NF-kappaB-mediated cytokine release and thus the immune response. Curcumin treatment also showed anti-microbial activity, it abolished the adherence of bacteria to cells in late infection.
3. Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispensable with ectopic expression of Smac or downregulation of Bcl-XL.
Rashmi R, Kumar S, Karunagaran D
Carcinogenesis. 2005 Apr;26(4):713-23.
Bax, from the Bcl-2 family, is a proapoptotic protein that can be induced to undergo conformational changes by multiple apoptotic stimuli. A Bax deficiency has been associated with chemoresistance in colon adenocarcinomas. This study investigated the role of Bax in curcumin-induced apoptosis. HCT116 human colon cancer cells that had one allele of Bax gene (Bax+/-) and Bax knockout HCT116 (Bax-/-) were used. Results showed that cell viability decreased concentration dependently in curcumin-treated Bax +/- cells, but there were only minimal changes in cell viability in curcumin treated Bax -/- cells. Curcumin activated caspase 9 and 3 but was blocked in Bax-/- cells. Cytochrome c, Second mitochondria derived activator of caspase (Smac) and apoptosis inducing factor (AIF) were also induced by curcumin but blocked in Bax-/- cells. There was no difference in percentage of apoptotic cells in Bak RNAi transfected Bax+/- or Bax-/- cells treated with curcumin when compared with their corresponding vector transfected cells treated with curcumin. This demonstrates that Bax, not Bak is a critical regulator of curcumin-induced apoptosis.
4. Constitutive activation of transcription factor AP-1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and AP-1 activity in HeLa cells by curcumin.
Prusty BK, Das BC
Int J Cancer. 2005 Mar 1; 113(6): 951-60.
The binding activity of AP-1 and the expression pattern of members of the AP-1 transcription factor family (c-Jun, JunB, JunD, c-Fos, FosB, Fra-1 and Fra-2) in grades of cervical lesions (from mild dysplasia to invasive cervical tumors) were investigated. AP-1 had high binding activity and most of the members were highly expressed in tumor tissues, but there is a gradual increase in c-Fos and decrease in Fra-1 expression that match cervical lesion progression. Curcumin can downregulate HPV18 transcription and AP-1 binding activity in HeLa cells. Curcumin can also reverse the expression dynamics of c-Fos and Fra-1 in HeLa cells. This study gives a basis to develop a new therapeutic approach to control pathogenic HPV infection through the use of antioxidative agents.
5. Antitumor effects of cpossibleurcumin, alone or in combination with cisplatin or doxorubicin, on human hepatic cancer cells. Analysis of their relationship to changes in NF-kB activation levels and in IAP gene expression.
Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, D’Alessandro N
Cancer Lett. 2005 Jun 16;224(1):53-65.
The hepatic cancer HA22T/VGH cell line expresses activated nuclear factor-kappaB (NF-kB). This cell line was chosen in this study to examine the antitumor activity of curcumin, and its relationship to influences on the activation of the transcription factor and the expression of the inhibitory of apoptosis proteins (IAPs) and of other NF-kB target genes. Curcumin showed to inhibit cell growth and had apoptotic effects that is somewhat related to free radical generation and is dependent on caspase-9 and –3 activation. Curcumin and cisplatin together showed to have a synergistic antitumor activity. Curcumin with doxorubicin showed to have additivity. Curcumin increased NF-kB levels at 8h and decreased it at 16h.
6. Thioredoxin reductase is irreversibly modified by curcumin: A novel molecular mechanism for its anticancer activity.
Fang J, Lu J, Holmgren A.
J Biol Chem. 2005 Jul 1;280(26):25284-90.
TrxR1 in the cytosol and nucleus and TrxR2 in mitochondria, are mammalial selenocysteine (Sec)-containing flavoenzymes. TxRs catalyze the NADPH-dependent reduction of the active site disulfide in thioredoxins (Trxs), which play essential roles in substrate reductions, defense against oxidative stress, and redox regulation by thiol redox control. This study reports that rat TrxR1 activity in Trx-dependent disulfide reduction was inhibited by curcumin. The IC(50) value for the enzyme was 3.6 microM after incubation at room temperature for 2 h in vitro. Modification of TrxR by curcumin provides a possible mechanistic explanation for its cancer preventive activity, shifting the enzyme from an antioxidant to a prooxidant.
7. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raji proliferation.
Liu HL, Chen Y, Cui GH, Zhou JF.
Acta Pharmacol Sin. 2005 May; 26(5): 603-9.
AIM: To investigate curcumin (diferuloylmethane) induced apoptosis and its molecular mechanism of action in B-NHL cell line Raji cells. CONCLUSION: Curcumin, as a new member of the histone deacetylase inhibitors, can inhibit the expression of class I HDACs (HDAC1, HDAC3, and HDAC8), and can increase the expression of Ac-histone H4 in Raji cells. Curcumin plays an important role in regulating B-NHL cell line Raji cell proliferation and apoptosis.
8. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences.
Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ.
Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):120-5.
Curcumin reduces the adenoma burden in rodent models of colorectal cancer. This is accompanied by a reduction in levels of the oxidative DNA adduct 3-(2-deoxy-beta-di-erythro-pentafuranosyl)-pyr[1,2-alpha]-purin-10(3H)one (M(1)G) and expression of COX-2. Colorectal cancer patients were given curcumin capsules (3,600, 1,800 or 450 mg daily) for a week. The concentrations of curcumin in normal and malignant colorectal tissue of patients receiving 3,600 mg of curcumin were 12.7 +/- 5.7 and 7.7 +/- 1.8 nmol/g, respectively. Trace levels of curcumin were found in the peripheral circulation. M(1)G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P < 0.05 by ANOVA). Trace levels of curcumin were found in the peripheral circulation. M(1)G levels were 2.5-fold higher in malignant tissue as compared with normal tissue (P < 0.05 by ANOVA).
9. Synthesis and antitumor activity of some curcumin analogs.
Youssef KM, El-Sherbeny MA
Arch Pharm (Weinheim). 2005 Apr; 338(4):181-9.
Four curcumin analogs (compounds 1, 2, 17 and 18) were synthesized. 17 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)N-methylpiperidone] showed high activity with GI50, TGI, and LC50 MG-MID values of 21.3, 70.7, and 97.7 microM, respectively. 18 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)-N-ethylpiperidone] showed the highest activity in this study with GI50, TGI, LC50 MG-MID values of 4.4, 33.8, 89.1 microM, respectively. The antioxidant effect of these compounds depends mainly on the stabilization of the formed phenoxy free radical for which the p-hydroxy phenyl moiety is essential. o-substitution by electron-donating groups like the o-methoxy group (and to a even higher degree by the ethoxy group) increases the stability of phenoxy free radical, hence increasing both free scavenging and anti-tumor effects.
10. Induction of apoptosis by curcumin and its implications for cancer therapy.
Karunagaran D, Rashmi R, Kumar TR
Curr Cancer Drug Targets. 2005 Mar; 5(2):117-29.
Apoptosis induced by curcumin involves mitochondria-mediated pathway in various cancer cells. In some cells, curcumin induces apoptosis-like changes but in primary cells, they do not induce apoptosis. This review describes the mechanisms of curcumin-induced apoptosis currently known, and suggests several potential strategies that include down-regulation of antiapoptotic proteins by antisense oligonucleotides, use of proapoptotic peptides and combination therapy, and other novel approaches against chemoresistant tumors
11. The effect of curcumin on bladder cancer cell line EJ in vitro
Sun M, Yang Y, Li H, Su B, Lu Y, Wei Q, Fan T
Zhong Yao Cai. 2004 Nov;27(11):848-50
OBJECTIVE: To observe the effect of curcumin on bladder cancer cell line EJ in vitro.. CONCLUSIONS: Curcumin can suppress the growth, induce apoptosis of bladder cancer EJ cell in vitro. Its mechanism is related with down-regulations of the expressions of NF-kappaB and Cyclin D1. Curcumin has great potential for the treatment of bladder cancer.
12. Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma.
Uddin S, Hussain AR, Manogaran PS, Al-Hussein K, Platanias LC, Gutierrez MI, Bhatia KG
Oncogene. 2005 Jul 25
Curcumin inhibits cell proliferation and induces apoptosis dose-dependently in many primary effusion lymphoma (PEL) cell lines. Curcumin suppresses STAT3 by inhibiting Janus kinase 1 (JAK-1). This leads to inhibition of proliferation and induction of caspase-dependent apoptosis.
13. Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1).
Chearwae W, Wu CP, Chu HY, Lee TR, Ambudkar SV, Limtrakul P
Cancer Chemother Pharmacol. 2005 Jul 14;:1-13.
Chemotherapy failure is commonly caused by multidrug resistance. This resistance is due to overexpression of drug pumps such as P-glycoprotein and multidrug resistance protein 1 (MRP1). This study tests crcumin mixture and three major crcuminoids for their ability to modulate MRP1 function. Curcuminoids inhibit MRP 1-mediated transport and among crcuminoids, curcumin I, which is a major constituent of crcumin mixture is the best modulator.
14. Effect of Curcumin on Caspase 8- and Caspase 9- induced Apop-tosis of Lymphoma Raji Cell
Wu Q, Chen Y, Li XG
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2005 Aug;13(4):624-7.
This study investigate the anticancer activities of Curcumin. Raji cells (lymphoma cell line) and peripheral blood mononuclear cells (PBMNC) were treated with varying concentrations of curcumin, inhibition rates were examined. Also, expressions of caspase 8 and caspase 9 in Raji cells were detected by Western blot. Curcumin inhibits proliferation of Raji cells in a dose- and time-dependent manner. Curcumin can enhance Raji cell apoptosis at 25 micromol/L and 24 hours (P < 0.01). Curcumin had no effect on PBMNC.
15. Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells.
Tomita M, Kawakami H, Uchihara JN, Okudaira T, Masuda M, Takasu N, Matsuda T, Ohta T, Tanaka Y, Ohshiro K, Mori N. Int J Cancer. 2005 Aug 16.
Adult T-cell leukemia (ATL) is an incurable malignancy of T lymphocytes caused by infection with human T-cell leukemia virus type I (HTLV-I). Curcumin is examined for its effectiveness in treating ATL. Curcumin prevent cell growth of T-cell lines infected by HTLV-I and primary ATL cells. It also induced cell cycle arrest, and suppressed constitutive active NF-kappaB of HTLV-I-infected T-cell lines and primary ATL cells by inhibition of IkappaBalpha phosphorylation. Curcumin inhibited growth of HTLV-I infected T-cell tumors implanted subcutaneously in SCID mice. Curcumin has tumor-suppressive activity against ATL.
16. Preparation and anti-inflammatory activities of diarylheptanoid and diarylheptylamine analogs.
Lee SL, Huang WJ, Lin WW, Lee SS, Chen CH.
Bioorg Med Chem. 2005 Aug 3
Seven diarylheptylamine (12a-g) and four diarylheptanoid analogs (3-5, 9) were prepared from curcumin to evaluate their activity against iNOS and COX-2 expression. Diarylheptylamine 12b and diarylheptanoid analogs inhibit iNOS and COX-2, but less potently than oregonin.
17. Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells.
Fullbeck M, Huang X, Dumdey R, Frommel C, Dubiel W, Preissner R.
BMC Cancer. 2005 Aug 5;5:97.
Curcumin stabilizes p53, a tumor suppressor. This is done by inhibiting COP9 signalosome (CSN) associated kinases CK2 and PKD. Curcumin and emodin block CSN-directed c-Jun signaling pathway. This study aimed to look for new CSN kinase inhibitors that is similar to Curcumin and emodin. There are 3 curcumin group compounds and 4 emodin group compounds that were found to be potent inhibitors of CSN-associated kinases. They increased p53 levels and induced apoptosis in tumor cells.
18. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR.
Tang XQ, Bi H, Feng JQ, Cao JG
Acta Pharmacol Sin. 2005 Aug;26(8):1009-16.
This study investigated the reversal effects of Curcumin on multidrug resistance (MDR) in a resistant human gastric carcinoma cell line. Curcumin at concentrations up to 20 micromol/L had no cytotoxic effect on a human gastric carcinoma cell line or its vincristine (VCR)-resistant variant cell line. Results showed that Curcumin can reverse the MDR of the human gastric carcinoma SGC7901/VCR cell line.
19. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway.
Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R.
Cancer. 2005 Aug 15;104(4):879-90.
The study focused on the possibility of using curcumin as an inhibitor of nuclear factor-kappaB (NF-kappaB) for use in melanoma treatment. Three melanoma cell lines were treated with curcumin and were assessed for viability and apoptosis. They were also examined for NF-kappaB binding activity and IkappaB kinase (IKK) activity. Results showed that curcumin decreased cell viability in all 3 cells lines dose-dependently, and induced apoptosis. NF-kappaB and IKK were active in all melanoma cell lines, and their activities were down-regulated when treated with curcumin.
20. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway.
Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R.
Cancer. 2005 Aug 15;104(4):879-90.
The study focused on the possibility of using curcumin as an inhibitor of nuclear factor-kappaB (NF-kappaB) for use in melanoma treatment. Three melanoma cell lines were treated with curcumin and were assessed for viability and apoptosis. They were also examined for NF-kappaB binding activity and IkappaB kinase (IKK) activity. Results showed that curcumin decreased cell viability in all 3 cells lines dose-dependently, and induced apoptosis. NF-kappaB and IKK were active in all melanoma cell lines, and their activities were down-regulated when treated with curcumin.
21. Evaluation of a new copper(II)-curcumin complex as superoxide dismutase mimic and its free radical reactions.
Barik A, Mishra B, Shen L, Mohan H, Kadam RM, Dutta S, Zhang HY, Priyadarsini KI.
Free Radic Biol Med. 2005 Sep 15; 39(6):811-22.
A synthesized form of mononuclear (1:1) copper complex of curcumin was examined for its superoxide dismuatase (SOD) activity. The Cu(II)-curcumin complex is soluble in lipids and DMSO, but is insoluble in water. Cu(II)-curcumin has SOD activity, free radical neutralizing ability and antioxidant potentials.
22. Expression profiles of apoptotic genes induced by curcumin in human breast cancer and mammary epithelial cell lines.
Ramachandran C, Rodrigues S, Ramachandran R, Raveendran Nair PK, Fonseca H, Khatib Z, Escalon E, Melnick SJ.
Anticancer Res. 2005 Sep-Oct; 25(5):3293-302.
Cytotoxic, apoptotic and gene regulatory effects of turmeric and Curcumin were studied in the MCF-7 human breast cancer carcinoma cell line, and this was compared to the effects of turmeric and Curcumin on the MCF-10A human mammary epithelial cells. MCF-10A retained less Curcumin than MCF-7 cells. There was a higher percentage of apoptosis in MCF-7 cells than in MCF-10A cells at all doses. Gene expression in MCF-7 were altered up to 14-fold and only up to 1.5-fold in MCF-10A cells. These results indicate that there may be potential in Curcumin for prevention and treatment of cancer.
23. Liposome-encapsulated curcumin.
Li L, Braiteh FS, Kurzrock R.
Cancer. 2005 Sep 15;104(6):1322-31.
Nuclear factor-kappaB (NF-kappaB) has been implicated in pancreatic carcinoma pathogenesis. Curcumin has potent NF-kappaB-inhibitory activity. Curcumin has poor bioavailability after oral administration. Researchers encapsulated Curcumin in a liposomal delivery system which allowed for intravenous administration. In vivo and in vitro effects of the encapsulated Curcumin were studied for proliferation, apoptosis, signaling and angiogenesis in human pancreatic carcinoma cells. Liposomal Curcumin suppressed NF-kappB binding and decreased expression of NF-kappaB regulated gene products. In vivo, Curcumin suppressed pancreatic carcinoma and inhibited tumor angiogenesis.
24. Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma.
Shishodia S, Amin HM, Lai R, Aggarwal BB.
Biochem Pharmacol. 2005 Sep 1;70(5):700-13.
Human mantle cell lymphoma (MCL) is an aggressive B cell non-Hodgkin’s lymphoma and is characterized by an overexpression of cyclin D1. MCL is resistant to current chemotherapy. MCL cells overexpress NF-kappaB gene products, so Curcumin was used to target NF-kappaB in MCL cell lines. Curcumin treatment of cells downregulated NF-kappaB and inhibited IkappaBalpha kinase (IKK) and phosphorylation of IkappaBalpha and p65. Overall, results indicate that curcumin inhibits the constitutive NF-kappaB and IKK leading to suppression of expression of NF-kappaB-regulated gene products that results in the suppression of proliferation, cell cycle arrest, and induction of apoptosis in MCL.
25. Chemopreventive effects of embelin and curcumin against N-nitrosodiethylamine/phenobarbital-induced hepatocarcinogenesis in Wistar rats.
Sreepriya M, Bali G.
Fitoterapia. 2005 Sep;76(6):549-55.
Effects of embelin and curcumin against N-nitrosodiethylamine (DENA)-initiated and phenobarbital (PB)-promoted hepatocarcinogenesis were studied in Wistar rats. Embelin and curcumin successfully prevented the induction of hepatic hyper plastic nodules, body weight loss, increase in the levels of hepatic diagnostic markers, and hypoproteinemia induced by DENA/PB treatment.
26. Inhibition of survival signalling by dietary polyphenols and indole-3-carbinol.
Manson MM
Eur J Cancer. 2005 Sep;41(13):1842-53.
This review outlines the different mechanisms of action of dietary polyphenols such as Curcumin, epigallocatechin gallate and resveratrol, which have anti-carcinogenic properties.
27. Establishment and Characterization of a Pancreatic Carcinoma Cell Line Derived from Malignant Pleural Effusion.
Starr AN, Vexler A, Marmor S, Konik D, Ashkenasi-Voghera M, Lev-Ari S, Greif Y, Ben-Yosef R.
Oncology. 2005 Sep 2;69(3):239-245.
This study aimed to characterize a novel cell line, designated p34. This p34 cell line can be used as a new model for studying various aspects of human pancreatic cancer. There were several in vitro studies such as karyotype analysis, immunohistochemistry, XTT cell proliferation assay, analysis of the cell cycle by FACS and cell sensitivity to chemotherapeutic drugs and irradiation. To study the cell line’s tumorigenicity and metastatic tendency, nude mice were inoculated at subcutaneous and intraspleen levels. The p34 cell line has similar morphological characteristics of epithelial pancreatic tumor cells. Inoculation of the cells subcutaneously brought 100% tumorigenicity. Chemotherapy, which included gemcitabine, cisplatin, taxol and vinorelbine, and chemopreventive agents such as celecoxib and curcumin and radiotherapy showed dose-dependent cytotoxicity.
28. Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity.
Fang J, Lu J, Holmgren A.
J Biol Chem. 2005 Jul 1;280(26):25284-90.
TrxR1 in the cytosol and nucleus and TrxR2 in mitochondria, are mammalial selenocysteine (Sec)-containing flavoenzymes. TxRs catalyze the NADPH-dependent reduction of the active site disulfide in thioredoxins (Trxs), which play essential roles in substrate reductions, defense against oxidative stress, and redox regulation by thiol redox control. This study reports that rat TrxR1 activity in Trx-dependent disulfide reduction was inhibited by curcumin. The IC(50) value for the enzyme was 3.6 microM after incubation at room temperature for 2 h in vitro. Modification of TrxR by curcumin provides a possible mechanistic explanation for its cancer preventive activity, shifting the enzyme from an antioxidant to a prooxidant.
29. Combined effects of GSTP1 and MRP1 in melanoma drug resistance.
Depeille P, Cuq P, Passagne I, Evrard A, Vian L.
Br J Cancer. 2005 Jul 25;93(2):216-23.
In melanoma, a skin cancer resistant to current therapy, glutathione-S-transferase Pi1 (GSTP1) and multidrug resistance protein 1 (MRP1) are overexpressed. Their involvement in drug resistance was investigated. An inducible antisense (AS) RNA strategy was used to inhibit GSTP1 expression in A375 cells. Transfectant clones were analyzed for GSTP1 inhibition by AS RNA. The clone A375-ASPi1, presenting a specific 40% inhibition of GSTP1 expression in the presence of doxycycline, was selected. ), GSTs (curcumin, ethacrynic acid), and also of MRPs (MK571, sulphinpyrazone) improved the sensitising effect of GSTP1 AS RNA. All these inhibitors had stronger sensitising effects in control cells expressing high GSTP1 level (A375-ASPi1 cells in the absence of doxycycline).
30. 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.
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.
31. 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 fialed to prevent liver tumors in LEC rats. Curcumin also had in vitro DNA damaging potential when presented with copper ions.
32. 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.
33. Inhibition of radiation induced nitration by curcumin and nicotinamide in mouse macrophages.
Narang H, Krishna M.
Mol Cell Biochem. 2005 Aug;27 6(1-2):7-13.
Irradiation of LPS activated mouse peritoneal macrophages increased NO production, iNOS expression and nitration of proteins. Curcumin, nicotinamide and Jun N-terminal kinase (JNK) inhibitor, SP600125 reduced levels of NO, iNOS expression and nitration of proteins. The JNK inhibitor did not decrease iNOS expression significantly, but it did significantly decrease NO production. Curcumin and JNK inhibitor inhibited the nitration of proteins.
34. Curcumin suppresses interleukin 1{beta}-mediated microsomal prostaglandin E synthase 1 (mPGES-1) by altering early growth response gene EGR-1 and other signaling pathways.
Moon Y, Glasgow WC, Eling TE
J Pharmacol Exp Ther. 2005 Aug 4.
One possible anti-inflammatory mechanism of Curcumin is the inhibition of prostaglandin E2 formation. Curcumin suppresses interleukin-1beta-induced formation of PGE2. mPGES-1 and cyclooxygenase-2 induced by IL-1b were lessened at protein and mRNA levels. Results concluded that curcumin inhibits IL-1b-induced PGE2 formation by inhibiting the expression of mPGES-1, which is mediated by suppression of EGR-1 expression as well as NF-kappaB and JNK ½.
35. Elucidation of anti-allergic activities of curcumin-related compounds with a special reference to their anti-oxidative activities.
Suzuki M, Nakamura T, Iyoki S, Fujiwara A, Watanabe Y, Mohri K, Isobe K, Ono K, Yano S.
Biol Pharm Bull. 2005 Aug;28(8):1438-43.
The anti-allergic and anti-oxidative activities of curcumin and its related compounds were studied to understand the mechanisms curcumin exerts to have these properties. Anti-allergic activities were assessed by histamine release from a rat basophilic leukemia cell, curcumin decreased histamine release markedly. Curcumin glycosides inhibited histamine release as well, but was not as potent in reducing it as curcumin. Anti-oxidative properties were measured by cellular radical scavenging. Curcumin and all compounds with the exception of diglycosides and bisdemethoxycurcumin had anti-oxidative effects. All Curcumin compounds that had scavenging properties also caused a decrease in histamine release, suggesting that curcumin’s hydroxy groups have a significant role in these properties.
36. Curcumin Blocks Interleukin-1 (IL-1) Signaling by Inhibiting the Recruitment of the IL-1 Receptor-Associated Kinase IRAK in Murine Thymoma EL-4 Cells.
Jurrmann N, Brigelius-Flohe R, Bol GF
J Nutr. 2005 Aug;135(8):1859-64.
Curcumin may have anti-inflammatory and anticarcinogenic effects because of the modification of protein thiols, which alter the activity of the affected proteins. IL-1 is stimulated when IL-1 receptor-associated kinase (IRAK) is recruited to the IL-1 receptor. IRAK is inhibited by agents that modify thiols of IRAK. Curcumin blocked IRAK thiols in a murine T-cell line, which inhibits IRAK, therefore inhibiting IL-1 activity. Thiol modification may be crucial in understanding how curcumin has anti-inflammatory properties.
37. The relationship between the anti-inflammatory effects of curcumin and cellular glutathione content in myelomonocytic cells.
Strasser EM, Wessner B, Manhart N, Roth E
Biochem Pharmacol. 2005 Aug 15;70(4):552-9.
This study investigates the impact of GSH modulating effects of curcumin on inflammatory processes in myelomonocytic U937 cells. Administration of 10 micromol/l of curcumin significantly increased reactive oxygen species (ROS) production in the U937 cells after an hour. Within twenty-four hours, ROS concentration was decreased significantly, and GSH and GSSG content increased. Curcumin at a concentration of 25 micromol/l caused a greater increase of GSH and GSSG, but decreased the percentage of living cells. It can be concluded that curcumin’s antioxidative effects are preceded by an oxidative stimulus, and that excessive concentrations of curcumin may harm cells.
38. Stimulation of Macrophage Migration Inhibitory Factor Expression in Endometrial Stromal Cells by Interleukin 1, beta Involving the Nuclear Transcription Factor NF{kappa}B.
Cao WG, Morin M, Metz C, Maheux R, Akoum A
Biol Reprod. 2005 Sep;73(3):565-70.
Interleukin 1 (IL1) is a major proinflammatory cytokine overproduced by women-derived peritoneal macrophages and in the peritoneal fluid of patients with endometriosis. It also stimulates the synthesis and secretion of macrophage migration inhibitory factor (MIF) by human endometrial stromal cells. IL1B induces MIF gene transcription thru the kappaB nuclear transcription factor (NfkappaB). Curcumin inhibits NfkappaB activation, this showed to inhibit IL1B-induced MIF secretion as well as NfkappaB nuclear translocation and DNA binding.
39. Interleukin-17--induced interleukin-8 release in human airway smooth muscle cells: role for mitogen-activated kinases and nuclear factor-kappaB.
Wuyts WA, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE, Demedts MG, Verleden GM.
J Heart Lung Transplant. 2005 Jul;24(7):875-81.
IL-17 stimulated human airway smooth muscle cells (HASMC) produce IL-8. This study investigates whether p38 mitogen-activated protein kinase (MAPK), c-Jun amino-terminal kinase (JNK), p42/44 extracellular signal-related kinase (ERK) and nuclear factor-kappaB (NF-kappaB) are involved in IL-8 production induced by IL-17 in HASMC in vitro. Cultured human airway smooth muscle cells were used. Curcumin, which is a specific inhibitor of JNK, reduced IL-17—induced IL-8 production concentration-dependently. U0126 induced a maximal decrease of p42/p44 ERK. Pyrrolydine dithiocarbamate (PDTC), which inhibits NF-kappaB, decreased IL-8 production.
40. Effect of anti-inflammatory and antioxidant drugs on the long-term repair of severely injured mouse skeletal muscle.
Vignaud A, Cebrian J, Martelly I, Caruelle JP, Ferry A
Exp Physiol. 2005 Jul;90(4):487-95.
Anti-inflammatory drugs are prescribed after skeletal muscle injury. Animals were tested for 10-14 days with different types of anti-inflammatory and antioxidant drugs. Results showed that diclofenac, difleruloylmethane (curcumin), dimethylthiourea or pyrrolidine dithiocarbamate treatment did not affect muscle recovery after myotoxic injury. Diferuloylmethae, dimethyl sulphoxide and indomethacin did not change muscle repair after crush injury, but high doses of diferuloylmethane and indomethacin increased lethality and reduced muscle repair after crush injury.
41. Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines.
Tomita M, Kawakami H, Uchihara JN, Okudaira T, Masuda M, Takasu N, Matsuda T, Ohta T, Tanaka Y, Mori N.
Leuk Res. 2005 Sep 9; [Epub ahead of print].
Activation of the activator protein 1 (AP-1) plays a critical role in oncogenesis by human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent of adult T-cell leukemia (ATL), and is required for maintenance of the malignant phenotype. This study examined the effects of curcumin on AP-1 activity in HTLV-1-infected T-cell lines. Curcumin suppressed the constitutive AP-1 DNA-binding and transcriptional activity in HTLV-1-infected T-cell line. Curcumin also inhibited HTLV-1 Tax-induced AP-1 transcriptional activity. JunD was detectable as a major component of the AP-1-DNA complex in HTLV-1-infected T-cell lines using the supershift assay. The expression of JunD was suppressed by curcumin treatment. Curcumin inhibited the growth of HTLV-1-infected T-cell lines by inducing cell cycle arrest followed by apoptosis. Our results suggest that suppression of the constitutively active AP-1 by curcumin is due to, at least in-part, reducing the expression of JunD by curcumin. Inhibition of AP-1 activity by curcumin may be one of the mechanisms responsible for the anti-ATL effect of curcumin.
2. Cystic Fibrosis
1. Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity.
Berger AL, Randak CO, Ostedgaard LS, Karp PH, Vermeer DW, Welsh MJ.
J Biol Chem. 2005 Feb 18; 280(7): 5221-6.
Treating cystic fibrosis (CF) may be helped by compounds that enhance the function or processing of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. There have been several studies that suggested that curcumin may affect the processing of a CF mutant, CFTR-DeltaF508. This study tests whether or not curcumin influences channel function. Curcumin increased CFTR channel activity in inside-out membrane patches. Curcumin maintained the channels to be open for a longer time. Curcumin stimulation was dose-dependent and had greater effects than genistein, which also stimulates CFTR. It increased the activity of wild-type and DeltaF508 channels, and also increased Cl(-) transport in differentiated non-CF airway epithelia.
2. Zedoariae rhizoma and curcumin inhibits platelet-derived growth factor-induced proliferation of human hepatic myofibroblasts.
Park SD, Jung JH, Lee HW, Kwon YM, Chung KH, Kim MG, Kim CH.
Int Immunopharmacol. 2005 Mar;5(3):555-69.
The aim of this study was to test the effects of ZR on the proliferation and to clarify the molecular mechanisms of ZR inhibition of HSC proliferation in cultured human hMF. The cells were stimulated by platelet-derived growth factor (PDGF)-BB in the presence or absence of ZR. Proliferation was determined by bromodeoxy-uridine (BrdU) incorporation. The mRNA expressions of collagen alpha1(I) and (IV) were evaluated by a quantitative reverse transcription-polymerase chain reaction (RT-PCR). PDGF-receptor tyrosine phosphorylation was detected using anti-phosphotyrosine antibody. PDGF-receptor radioligand binding assay was performed by [125I]PDGF-BB. ZR inhibited the PDGF-BB-induced cell-proliferation and collagen alpha1(I) and (IV) mRNA expressions. ZR reduced the autophosphorylation of the PDGF-receptor. ZR blocked PDGF-BB binding to its receptor in a non-competitive manner. Furthermore, the 80% aqueous acetone extract of ZR was also found to show a decreasing effect against the proportion of S phase cells after PDGF stimulation. To clarify the active compounds, the principal constituents of seven sesquiterpenes (curdione, dehydrocurdione, germacrone, curcumenol, isocurcumenol, zedoarondiol and curcumenone) and a diarylheptanoid (curcumin) were examined. Among them, curcumin was found to decrease the proportion of S phase cells after PDGF stimulation at a dose of 30-50 microM.
3. Curcumin prevents methylglyoxal-induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts.
Hsuuw YD, Chang CK, Chan WH, Yu JS
J Cell Physiol. 2005 May 10.
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. The effect of curcumin on apoptotic biochemical events caused by incubation of ESC-B5 cells with MG was studied.Curcumin inhibited the MG-induced DNA fragmentation, caspase-3 activation, cleavage of PARP, mitochondrial cytochrome c release, and JNK activation.
Importantly, curcumin also inhibited the MG-stimulated increase of reactive oxygen species (ROS) in these cells. In addition, we demonstrated that curcumin prevented the MG-induced apoptosis of mouse blastocysts isolated from pregnant mice. Moreover, curcumin significantly reduced the MG-mediated impairment of blastocyst development from mouse morulas.
3. Wound Healing
1. Curcumin treatment enhances the repair and regeneration of wounds in mice exposed to hemibody gamma-irradiation.
Jagetia GC, Rajamikant GK
Plast Reconstr Surg. 2005 Feb;115(2):515-28.
Hemibody irradiation in multiple fractionated doses is frequently used for the treatment of various neoplastic disorders. It produces both acute and late effects on the skin and subcutaneous tissues that have profound implications in the healing of surgical wounds.
Curcumin pretreatment has a conducive effect on the irradiated wound and could be a helpful therapeutic strategy for improving radiation-induced delay in wound repair in cases or radiation-induced injuries.
4. Gastroprotective/antiulcer
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.
II. Cardiovascular and Blood sugar support/diabetes/secondary complications support
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.
III. Antioxidant
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.
IV Antimicrobial and Antiangiogenic
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.
V. Antiviral: HIV/BSE/TSE
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.
VI. Biological and Pharmacological
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 preparati
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