Biological Properties of Curcumin-Cellular and Molecular Mechanisms of Action

Curcuminoids, a group of phenolic compounds isolated from the roots of Curcuma longa (Zingiberaceae), exhibit a variety of beneficial effects on health and on events that help in preventing certain diseases. A vast majority of these studies were carried out with curcumin (diferuloyl methane), which is a major curcuminoid. The most detailed studies using curcumin include anti-inflammatory, antioxidant, anticarcinogenic, antiviral, and antiinfectious activities. In addition, the wound healing and detoxifying properties of curcumin have also received considerable attention. As a result of extensive research on the therapeutic properties of curcumin, some understanding on the cellular, molecular, and biochemical mechanism of action of curcumin is emerging. These findings are summarized in this review.

[1]  L. O’Neill,et al.  Inhibition of nuclear factor kappaB by direct modification in whole cells--mechanism of action of nordihydroguaiaritic acid, curcumin and thiol modifiers. , 1998, Biochemical pharmacology.

[2]  Jen-kun Lin,et al.  Biotransformation of curcumin through reduction and glucuronidation in mice. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[3]  D. Shoskes,et al.  The effect of mycophenolate mofetil and polyphenolic bioflavonoids on renal ischemia reperfusion injury and repair. , 2000, The Journal of urology.

[4]  Y. Awasthi,et al.  Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver. , 1998, The international journal of biochemistry & cell biology.

[5]  B. Aggarwal,et al.  Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. , 1995, The Journal of biological chemistry.

[6]  B. H. Shah,et al.  Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. , 1999, Biochemical pharmacology.

[7]  Ashutosh Kumar Singh,et al.  Curcumin enhances wound healing in streptozotocin induced diabetic rats and genetically diabetic mice , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[8]  V. Lad An introduction to Ayurveda. , 1995, Alternative therapies in health and medicine.

[9]  N. Shirasaka,et al.  Inhibition of rat liver microsomal desaturases by curcumin and related compounds. , 1996, Bioscience, biotechnology, and biochemistry.

[10]  Seon-Hwa Lee,et al.  Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous Genotoxins , 2001, Science.

[11]  D. Karunagaran,et al.  L-929 Cells Harboring Ectopically Expressed RelA Resist Curcumin-induced Apoptosis* , 2000, The Journal of Biological Chemistry.

[12]  H. Kleinman,et al.  Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. , 1998, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[13]  K. Ferrell,et al.  Comparison of human COP9 signalosome and 26S proteasome ‘lid’ , 1999, Molecular Biology Reports.

[14]  O A Iakimenko,et al.  [Anti-inflammatory agents]. , 1984, Fel'dsher i akusherka.

[15]  T. Masuda,et al.  Protective actions of 5'-n-alkylated curcumins on living cells suffering from oxidative stress. , 1998, European journal of pharmacology.

[16]  J. Williams,et al.  Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and NF-kappa B. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[17]  B. Aggarwal,et al.  Activation of Transcription Factor NF-κB Is Suppressed by Curcumin (Diferuloylmethane) (*) , 1995, The Journal of Biological Chemistry.

[18]  Ashutosh Kumar Singh,et al.  Enhancement of wound healing by curcumin in animals , 1998, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[19]  G. Pavlath,et al.  Systemic administration of the NF-κB inhibitor curcumin stimulates muscle regeneration after traumatic injury. , 1999, American journal of physiology. Cell physiology.

[20]  S. Han,et al.  Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappa B, and p53. , 1999, Clinical immunology.

[21]  A. Mukherjee,et al.  Studies on the anticlastogenic effect of turmeric and curcumin on cyclophosphamide and mitomycin C in vivo. , 1998, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[22]  M. Hung,et al.  Curcumin inhibits tyrosine kinase activity of p185neu and also depletes p185neu. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  H. Ohshima,et al.  Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages. , 1995, Biochemical and biophysical research communications.

[24]  K. N. Rajasekharan,et al.  Antimutagenic and anticarcinogenic activity of natural and synthetic curcuminoids. , 1996, Mutation research.

[25]  M. Klagsbrun,et al.  AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells. , 1999, American journal of physiology. Cell physiology.

[26]  R. Srimal,et al.  Pharmacology of diferuloyl methane (curcumin), a non‐steroidal anti‐inflammatory agent * , 1973, The Journal of pharmacy and pharmacology.

[27]  M. Rao,et al.  Nitric Oxide Scavenging by Curcuminoids , 1997, The Journal of pharmacy and pharmacology.

[28]  K. Frenkel,et al.  Inhibitory effects of curcumin on tumorigenesis in mice , 1997, Journal of cellular biochemistry. Supplement.

[29]  V. Steele,et al.  Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. , 2000, The Journal of nutrition.

[30]  P. Verger,et al.  Estimation of the distribution of the maximum theoretical intake for ten additives in France. , 1998, Food additives and contaminants.

[31]  B. Lokesh,et al.  Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats. , 1996, Toxicology.

[32]  D. Zhou,et al.  Curcumin inhibits cell proliferation by interfering with the cell cycle and inducing apoptosis in colon carcinoma cells. , 1999, Anticancer research.

[33]  C. Boone,et al.  Biomarker end-points in cancer chemoprevention trials. , 1997, IARC scientific publications.

[34]  T. Miyata,et al.  Methylglyoxal induces apoptosis in Jurkat leukemia T cells by activating c‐Jun N‐Terminal kinase , 2000, Journal of cellular biochemistry.

[35]  M. Bertagnolli,et al.  Inhibition of intestinal tumors by curcumin is associated with changes in the intestinal immune cell profile. , 2000, The Journal of surgical research.

[36]  Y. P. Lu,et al.  Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion. , 1995, Carcinogenesis.

[37]  B. Aggarwal,et al.  Curcumin (Diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappaB activation. , 1998, Biochemical pharmacology.

[38]  M. K. Heng,et al.  Drug‐induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters , 2000, The British journal of dermatology.

[39]  E. Bahraoui,et al.  Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1 human immunodeficiency virus long terminal repeat. , 1998, Research in virology.

[40]  K. Kohn,et al.  Hydroxylated aromatic inhibitors of HIV-1 integrase. , 1995, Journal of medicinal chemistry.

[41]  B. Joe,et al.  Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. , 1994, Biochimica et biophysica acta.

[42]  K. Srinivasan,et al.  Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats , 2004, Molecular and Cellular Biochemistry.

[43]  H. Ammon,et al.  Pharmacology of Curcuma longa , 1991, Planta medica.

[44]  B. Joe,et al.  Dietary n-3 fatty acids, curcumin and capsaicin lower the release of lysosomal enzymes and eicosanoids in rat peritoneal macrophages , 2004, Molecular and Cellular Biochemistry.

[45]  N. Sreejayan,et al.  Free radical scavenging activity of curcuminoids. , 1996, Arzneimittel-Forschung.

[46]  Jen-kun Lin,et al.  Stability of curcumin in buffer solutions and characterization of its degradation products. , 1997, Journal of pharmaceutical and biomedical analysis.

[47]  C. Rao,et al.  Chemoprevention of Colon Cancer by Dietary Curcumin , 1995, Annals of the New York Academy of Sciences.

[48]  R. Puvanakrishnan,et al.  Effect of curcumin on certain lysosomal hydrolases in isoproterenol-induced myocardial infarction in rats. , 1996, Biochemical pharmacology.

[49]  R. Puvanakrishnan,et al.  Effect of curcumin on cetrain lysosomal hydrolases in isoproterenol-induced myocardial infarction in rats , 1996 .

[50]  Huei-Wen Chen,et al.  Effect of curcumin on cell cycle progression and apoptosis in vascular smooth muscle cells , 1998, British journal of pharmacology.

[51]  T. Luther,et al.  The Dietary Pigment Curcumin Reduces Endothelial Tissue Factor Gene Expression by Inhibiting Binding of AP-1 to the DNA and Activation of NF-κB , 1997, Thrombosis and Haemostasis.

[52]  H. Ciolino,et al.  Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells. , 1998, Biochemical pharmacology.

[53]  Jen-kun Lin,et al.  Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin , 1997, Journal of cellular biochemistry. Supplement.

[54]  B. Rigas,et al.  Curcumin, a natural plant phenolic food additive, inhibits cell proliferation and induces cell cycle changes in colon adenocarcinoma cell lines by a prostaglandin-independent pathway. , 1997, The Journal of laboratory and clinical medicine.

[55]  R. Foresti,et al.  Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. , 2000, Free radical biology & medicine.

[56]  L. Stanberry,et al.  Plant products as topical microbicide candidates: assessment of in vitro and in vivo activity against herpes simplex virus type 2. , 1999, Antiviral research.

[57]  R. Lodha,et al.  Traditional Indian systems of medicine. , 2000, Annals of the Academy of Medicine, Singapore.

[58]  L. Howells,et al.  Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. , 2001, Cancer research.

[59]  M. Osborne,et al.  Phytochemicals as modulators of cancer risk. , 1999, Advances in experimental medicine and biology.

[60]  B. Joe,et al.  Effect of curcumin and capsaicin on arachidonic acid metabolism and lysosomal enzyme secretion by rat peritoneal macrophages , 1997, Lipids.

[61]  N. Chandrasekhara,et al.  Effect on curcumin on cholesterol gall-stone induction in mice. , 1992, The Indian journal of medical research.

[62]  C. Hertel,et al.  Beta-amyloid binds to p57NTR and activates NFkappaB in human neuroblastoma cells. , 1998, Journal of neuroscience research.

[63]  M. Sugano,et al.  Effect of natural food colorings on immunoglobulin production in vitro by rat spleen lymphocytes. , 1996, Bioscience, biotechnology, and biochemistry.

[64]  K. Srinivasan,et al.  Influence of dietary curcumin and cholesterol on the progression of experimentally induced diabetes in albino rat , 1995, Molecular and Cellular Biochemistry.

[65]  Y. Lou,et al.  Some Perspectives on Dietary Inhibition of Carcinogenesis: Studies with Curcumin and Tea , 1997, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[66]  D. Brenner,et al.  Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity. , 1999, Journal of immunology.

[67]  M. Jiang,et al.  Inhibition of HIV-1 Tat-mediated transactivation by quinacrine and chloroquine. , 1996, Biochemical and biophysical research communications.

[68]  T C Chou,et al.  Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells. , 1998, Carcinogenesis.

[69]  G. Kuttan,et al.  Immunomodulatory activity of curcumin. , 1999, Immunological investigations.

[70]  R. Puvanakrishnan,et al.  Curcumin treatment modulates collagen metabolism in isoprot3erenol induced myoxardial necrosis in rats , 1999, Molecular and Cellular Biochemistry.

[71]  N. Venkatesan,et al.  Curcumin prevents adriamycin nephrotoxicity in rats , 2000, British journal of pharmacology.

[72]  A. Tantaoui-Elaraki,et al.  Growth and toxigenesis of Aspergillus flavus isolates on selected spices. , 1997, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[73]  A G Renwick,et al.  An analysis of the possibility for health implications of joint actions and interactions between food additives. , 2000, Regulatory toxicology and pharmacology : RTP.

[74]  B. Lokesh,et al.  Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. , 1994, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[75]  M. Dikshit,et al.  Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart. , 1995, The Indian journal of medical research.

[76]  M. Giacca,et al.  Activation of transcription factor NF-kappaB by the Tat protein of human immunodeficiency virus type 1 , 1996, Journal of virology.

[77]  J. Lin,et al.  Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats. , 2000, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[78]  R. Gaynor,et al.  The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. , 1998, Nature.

[79]  S. Hwang,et al.  Curcumin inhibits Th1 cytokine profile in CD4+ T cells by suppressing interleukin‐12 production in macrophages , 1999, British journal of pharmacology.

[80]  Y. Surh,et al.  Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. , 1999, Mutation research.

[81]  T. Tan,et al.  Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin , 1998, Oncogene.

[82]  A. Conney,et al.  Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells. , 1997, Oncology research.

[83]  K. Kato,et al.  Stimulation of the stress-induced expression of stress proteins by curcumin in cultured cells and in rat tissues in vivo. , 1998, Cell stress & chaperones.

[84]  C. Rao,et al.  Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. , 1995, Cancer research.

[85]  L. Chaudhary,et al.  Regulation of Interleukin-8 Gene Expression by Interleukin-1β, Osteotropic Hormones, and Protein Kinase Inhibitors in Normal Human Bone Marrow Stromal Cells* , 1996, The Journal of Biological Chemistry.

[86]  A. Dinkova-Kostova,et al.  Relation of structure of curcumin analogs to their potencies as inducers of Phase 2 detoxification enzymes. , 1999, Carcinogenesis.

[87]  C. Crumpacker,et al.  Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[88]  B. Aggarwal,et al.  The p60 Tumor Necrosis Factor (TNF) Receptor-associated Kinase (TRAK) Binds Residues 344–397 within the Cytoplasmic Domain Involved in TNF Signaling (*) , 1995, The Journal of Biological Chemistry.

[89]  T. Osawa,et al.  Chemoprevention by curcumin during the promotion stage of tumorigenesis of mammary gland in rats irradiated with gamma-rays. , 1999, Carcinogenesis.

[90]  B. Pardhasaradhi,et al.  Curcumin mediated apoptosis in AK‐5 tumor cells involves the production of reactive oxygen intermediates , 1999, FEBS letters.

[91]  L. Antunes,et al.  Effects of the antioxidants curcumin and vitamin C on cisplatin-induced clastogenesis in Wistar rat bone marrow cells. , 2000, Mutation research.

[92]  K. Platel,et al.  Influence of dietary spices and their active principles on pancreatic digestive enzymes in albino rats. , 2000, Die Nahrung.

[93]  K. C. Srivastava,et al.  Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. , 1995, Prostaglandins, leukotrienes, and essential fatty acids.

[94]  Jen-kun Lin,et al.  Curcumin Inhibits SK-Hep-1 Hepatocellular Carcinoma Cell Invasion in vitro and Suppresses Matrix Metalloproteinase-9 Secretion , 1998, Oncology.

[95]  H. Cohly,et al.  Effect of turmeric, turmerin and curcumin on H2O2-induced renal epithelial (LLC-PK1) cell injury. , 1998, Free radical biology & medicine.

[96]  L. Howells,et al.  Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex , 1999, Oncogene.

[97]  C. Takahashi,et al.  Modulatory effects of curcumin on the chromosomal damage induced by doxorubicin in Chinese hamster ovary cells. , 1999, Teratogenesis, carcinogenesis, and mutagenesis.

[98]  R. Kumar,et al.  Inhibition of ligand-induced activation of epidermal growth factor receptor tyrosine phosphorylation by curcumin. , 1995, Carcinogenesis.

[99]  M. Chan,et al.  In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. , 1998, Biochemical pharmacology.

[100]  Jen-kun Lin,et al.  Induction of HSP70 gene expression by modulation of Ca+2 ion and cellular p53 protein by curcumin in colorectal carcinoma cells , 1996, Molecular carcinogenesis.

[101]  J. Pezzuto,et al.  Evaluation of the potential of cancer chemopreventive activity mediated by inhibition of 12-O-tetradecanoyl phorbol 13-acetate-induced ornithine decarboxylase activity , 1999, Archives of pharmacal research.

[102]  B. Joe,et al.  Prophylactic and therapeutic effects of n-3 polyunsaturated fatty acids, capsaicin, and curcumin on adjuvant induced arthritis in rats , 1997 .

[103]  G. Wu,et al.  The effect of curcumin on human B-cell immortalization by Epstein-Barr virus. , 1998, The American surgeon.

[104]  S. Gautam,et al.  Nonselective inhibition of proliferation of transformed and nontransformed cells by the anticancer agent curcumin (diferuloylmethane). , 1998, Biochemical pharmacology.

[105]  C. Franceschi,et al.  Apoptosis‐like, reversible changes in plasma membrane asymmetry and permeability, and transient modifications in mitochondrial membrane potential induced by curcumin in rat thymocytes , 1998, FEBS letters.

[106]  G. Kuttan,et al.  Inhibition of lung metastasis in mice induced by B16F10 melanoma cells by polyphenolic compounds. , 1995, Cancer letters.

[107]  Jen-kun Lin,et al.  Curcumin induces apoptosis in immortalized NIH 3T3 and malignant cancer cell lines. , 1996, Nutrition and cancer.

[108]  C. Hertel,et al.  β‐amyloid binds to p75NTR and activates NFκB in human neuroblastoma cells , 1998 .

[109]  T. Masuda,et al.  Chemical studies on antioxidant mechanism of curcumin: analysis of oxidative coupling products from curcumin and linoleate. , 2001, Journal of agricultural and food chemistry.

[110]  H. Ahsan,et al.  Strand scission in DNA induced by curcumin in the presence of Cu(II). , 1998, Cancer letters.

[111]  Y. P. Lu,et al.  Effect of dietary curcumin and dibenzoylmethane on formation of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and lymphomas/leukemias in Sencar mice. , 1998, Carcinogenesis.

[112]  Y. Awasthi,et al.  Curcumin protects against 4-hydroxy-2-trans-nonenal-induced cataract formation in rat lenses. , 1996, The American journal of clinical nutrition.

[113]  H. Ahsan,et al.  Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. , 1999, Chemico-biological interactions.

[114]  L. Leon,et al.  Biological activities of Curcuma longa L. , 2001, Memorias do Instituto Oswaldo Cruz.

[115]  F. Bonte,et al.  Protective effect of curcuminoids on epidermal skin cells under free oxygen radical stress. , 1997, Planta medica.

[116]  S. Onodera,et al.  Macrophage Migration Inhibitory Factor Up-regulates Expression of Matrix Metalloproteinases in Synovial Fibroblasts of Rheumatoid Arthritis* , 2000, The Journal of Biological Chemistry.

[117]  E. Sudharshan,et al.  Inhibition of lipoxygenase 1 by phosphatidylcholine micelles-bound curcumin , 1998, Lipids.

[118]  T. P. Krishnakantha,et al.  Influence of retinol deficiency and curcumin/turmeric feeding on tissue microsomal membrane lipid peroxidation and fatty acids in rats , 1997, Molecular and Cellular Biochemistry.

[119]  A. Sokal,et al.  Apoptosis-independent alterations in membrane dynamics induced by curcumin. , 1998, Experimental cell research.

[120]  R. C. Srimal,et al.  Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. , 1986, Arzneimittel-Forschung.

[121]  Y. Pommier,et al.  Curcumin analogs with altered potencies against HIV-1 integrase as probes for biochemical mechanisms of drug action. , 1997, Journal of medicinal chemistry.

[122]  K. Mohandas,et al.  Epidemiology of digestive tract cancers in India. V. Large and small bowel. , 1999, Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology.

[123]  M. Chan Inhibition of tumor necrosis factor by curcumin, a phytochemical. , 1995, Biochemical pharmacology.

[124]  J. Santibañez,et al.  Genistein and Curcumin Block TGF-β1-Induced u-PA Expression and Migratory and Invasive Phenotype in Mouse Epidermal Keratinocytes , 2000, Nutrition and cancer.

[125]  C. Takahashi,et al.  Potentiation by turmeric and curcumin of gamma-radiation-induced chromosome aberrations in Chinese hamster ovary cells. , 1999, Teratogenesis, carcinogenesis, and mutagenesis.

[126]  N. Ohta,et al.  Trypanocidal effects of curcumin in vitro. , 1998, Biological & pharmaceutical bulletin.

[127]  Rasyid,et al.  The effect of curcumin and placebo on human gall‐bladder function: an ultrasound study , 1999, Alimentary pharmacology & therapeutics.

[128]  B. Ghosh,et al.  Curcuma longa inhibits TNF-alpha induced expression of adhesion molecules on human umbilical vein endothelial cells. , 1999, International journal of immunopharmacology.

[129]  E. Skrzypczak‐Jankun,et al.  Curcumin inhibits lipoxygenase by binding to its central cavity: theoretical and X-ray evidence. , 2000, International journal of molecular medicine.

[130]  R. Gaynor,et al.  The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β , 1998, Nature.

[131]  M. Kottke Scientific and regulatory aspects of nutraceutical products in the United States. , 1998, Drug development and industrial pharmacy.

[132]  Jen-kun Lin,et al.  Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. , 2000, Carcinogenesis.

[133]  A. Wilson,et al.  Flavonoids, potent inhibitors of the human P-form phenolsulfotransferase. Potential role in drug metabolism and chemoprevention. , 1996, Drug metabolism and disposition: the biological fate of chemicals.

[134]  Jen-kun Lin,et al.  Curcumin, an antioxidant and anti-tumor promoter, induces apoptosis in human leukemia cells. , 1996, Biochimica et biophysica acta.

[135]  E. Sudharshan,et al.  Interaction of curcumin with human serum albumin—A spectroscopic study , 1999, Lipids.

[136]  D. Scholz,et al.  Ferula asa-foetida and Curcuma longa in traditional medical treatment and diet in Nepal. , 1999, Journal of ethnopharmacology.

[137]  G. Kuttan,et al.  Anti-metastatic activity of curcumin and catechin. , 1999, Cancer letters.

[138]  J. Exon,et al.  Dietary curcumin enhances antibody response in rats. , 1997, Immunopharmacology and immunotoxicology.

[139]  R. K. Bhattacharya,et al.  Action of curcumin on the cytochrome P450-system catalyzing the activation of aflatoxin B1. , 1996, Chemico-biological interactions.

[140]  S. Jee,et al.  Curcumin induces a p53-dependent apoptosis in human basal cell carcinoma cells. , 1998, The Journal of investigative dermatology.

[141]  R. Buttyan,et al.  Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo , 2001, The Prostate.

[142]  E. Novellino,et al.  Geometrically and conformationally restrained cinnamoyl compounds as inhibitors of HIV-1 integrase: synthesis, biological evaluation, and molecular modeling. , 1998, Journal of medicinal chemistry.

[143]  H. Yamamoto,et al.  Inhibitory effect of curcumin on mammalian phospholipase D activity , 1997, FEBS letters.

[144]  N. Vermeulen,et al.  Cytotoxicity and cytoprotective activities of natural compounds. The case of curcumin. , 1996, Xenobiotica; the fate of foreign compounds in biological systems.

[145]  Y. Oda,et al.  Inhibitory effect of curcumin on SOS functions induced by UV irradiation. , 1995, Mutation research.

[146]  K. Piwocka,et al.  Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment. , 1997, Biochemical pharmacology.

[147]  B. Joe,et al.  Presence of an acidic glycoprotein in the serum of arthritic rats: Modulation by capsaicin and curcumin , 1997, Molecular and Cellular Biochemistry.

[148]  B. Premalatha,et al.  Dietary curcumin with cisplatin administration modulates tumour marker indices in experimental fibrosarcoma. , 1999, Pharmacological Research.

[149]  U. Pastorino,et al.  Suppression of tumour development by substances derived from the diet--mechanisms and clinical implications. , 1998, British journal of clinical pharmacology.

[150]  G. Maru,et al.  Effects of curcumin on the formation of benzo[a]pyrene derived DNA adducts in vitro. , 1995, Cancer letters.

[151]  M. Majeed,et al.  Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. , 1998, Planta medica.

[152]  V. Steele,et al.  Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. , 1999, Cancer research.