Antioxidant effect of curcumin in selenium induced cataract of Wistar rats.
Wistar rat pups treated with curcumin, a natural constituent of Curcuma longa before being administered with selenium showed no opacities in the lens. The lipid peroxidation, xanthine oxidase enzyme levels in the lenses of curcumin and selenium co-treated animals were significantly less when compared to selenium treated animals. The superoxidase dismutase and catalase enzyme activities of curcumin and selenium co-treated animal lenses showed an enhancement. Curcumin co-treatment seems to prevent oxidative damage and found to delay the development of cataract.
Indian J Exp Biol. 2004 Jun;42(6):601-3
Time- and dose-dependent effects of curcumin on gene expression in human colon cancer cells.
BACKGROUND: Curcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling. METHODS: Gene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24, and 48 hours). Gene expression changes after short-term exposure (3 or 6 hours) to curcumin were also studied in a second cell type, Caco-2 cells. RESULTS: Gene expression changes (>1.5-fold) were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis. CONCLUSIONS: This study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase-II genes). Moreover, potential new leads to genes and pathways that could play a role in colon cancer prevention by curcumin were identified.
J Carcinog. 2004 May 12;3(1):8
Anticancer potential of curcumin: preclinical and clinical studies.
Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies.
Anticancer Res. 2003 Jan-Feb;23(1A):363-98
Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats.
Free radical induced neuronal damage is implicated in cerebral ischemia reperfusion (IR) injury and antioxidants are reported to have neuroprotective activity. Several in vitro and in vivo studies have proved the antioxidant potential of curcumin and its metabolites. Hence, in the present study the neuroprotective potential of curcumin was investigated in middle cerebral artery occlusion (MCAO) induced focal cerebral IR injury. 2 h of MCAO and 22 h of reperfusion resulted in the infarct volume of 210.39 +/- 31.25 mm3. Administration of curcumin 100 and 300 mg/kg, i.p. 30 min. after MCAO produced 37.23 +/- 5.10% and 46.39 +/- 10.23% (p < 0.05) reduction in infarct volume, respectively. Ischemia induced cerebral edema was reduced in a dose dependent manner. Curcumin at 300 mg/kg, i.p. produced 50.96 +/- 6.04% reduction in edema (p < 0.05) volume. Increase in lipid peroxidation after MCAO in ipsilateral and contralateral hemisphere of brain was observed, which was reduced by curcumin (300 mg/kg, i.p.)-treatment. Decrease in superoxide dismutase and glutathione peroxidase activity was observed in ipsilateral hemisphere of MCAO animal. Curcumin-treatment (300 mg/kg, i.p.) prevented IR injury mediated fall in glutathione peroxide activity. Peroxynitrite measured using rhodamine123 fluorescence and anti-nitrotyrosine immunofluorescence indicated increased peroxynitrite formation after IR insult. Curcumin-treatment reduced peroxynitrite formation and hence the extent of tyrosine nitration in the cytosolic proteins. These results suggest the neuroprotective potential of curcumin in cerebral ischemia and is mediated through its antioxidant activity.
Life Sci. 2004 Jan 9;74(8):969-85
Curcumin has potent anti-amyloidogenic effects for Alzheimer’s beta-amyloid fibrils in vitro.
Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the destabilization of preformed fAbeta in the central nervous system, would be attractive therapeutic targets for the treatment of Alzheimer’s disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAbeta formation from Abeta(1-40) and Abeta(1-42) and destabilize preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of curcumin (Cur) and rosmarinic acid (RA) on the formation, extension, and destabilization of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of Cur and RA with NDGA. Cur and RA dose-dependently inhibited fAbeta formation from Abeta(1-40) and Abeta(1-42), as well as their extension. In addition, they dose-dependently destabilized preformed fAbetas. The overall activities of Cur, RA, and NDGA were similar. The effective concentrations (EC(50)) of Cur, RA, and NDGA for the formation, extension, and destabilization of fAbetas were in the order of 0.1-1 microM. Although the mechanism by which Cur and RA inhibit fAbeta formation from Abeta and destabilize preformed fAbeta in vitro remains unclear, they could be a key molecule for the development of therapeutics for AD.
J Neurosci Res. 2004 Mar 15;75(6):742-50
Cholesterol and Alzheimer’s disease: clinical and experimental models suggest interactions of different genetic, dietary and environmental risk factors.
Alzheimer’s disease (AD) is a progressive senile dementia characterized by deposition of a 4 kDa peptide of 39-42 residues known as amyloid beta-peptide (Abeta) in the form of senile plaques and the microtubule associated protein tau as paired helical filaments. Genetic studies have identified mutations in the Abeta precursor protein (APP) as the key triggers for the pathogenesis of AD. Other genes such as presenilins 1 and 2 (PS1/2) and apolipoprotein E (APOE) also play a critical role in increased Abeta deposition. Several biochemical and molecular studies using transfected cultured cells and transgenic animals point to mechanisms by which Abeta is generated and aggregated to trigger the neurodegeneration that may cause AD. Three important enzymes collectively known as ‘secretases’ participate in APP processing leading to the generation of either Abeta or non-amyloid proteins. However, the mechanisms of neurotoxicity of Abeta and the role of APP function in AD remain important unanswered questions. Although early studies recognized the loss of cholesterol and other lipids in the brain, these findings have been poorly connected with AD pathogenesis, despite the identification of the epsilon4 allele of APOE as a major risk factor in AD. The recent finding that cholesterol can modulate the yield of potentially toxic Abeta has boosted research on its role in AD. Consequently, several cholesterol-reducing drugs are currently being evaluated for the treatment of AD. The present review summarizes our current understanding of the relationship of AD pathogenesis with cholesterol, lipids and other genetic and environmental risk factors.
Curr Drug Targets. 2004 Aug;5(6):517-28
Curcumin inhibits dose-dependently and time-dependently neuroglial cell proliferation and growth.
OBJECTIVES: Curcumin (CUR), the active chemical of the Asian spice turmeric, has strong anti-oxidant and anti-inflammatory properties. CUR inhibits proliferation and growth of several cell types, e.g. cancer cells. While CUR inhibitory effects on microglial cells are demonstrated, little is known of its effects on neuroglia, astrocytes (AST) and oligodendrocytes (OLG). Our work focuses on CUR’s effects on neuroglial proliferation and growth in vitro, utilizing C-6 rat glioma 2B-clone cells, a mixed colony of both neuroglial cells, in 6 day trials. METHODS: The doses studied included 4, 5, 10, 15, and 20 microM - concentrations slightly smaller than those shown to stimulate protein expression in ASTs. Automated particle counter was used to determine proliferation, and marker enzyme assays were used to determine AST and OLG activity. RESULTS: CUR inhibited neuroglial proliferation, with the degree of inhibition correlated directly with the CUR concentration. Proliferative inhibition was observed after a concentration as low as 5 microM by day 6, while inhibition of 20 microM doses occurred by day 2 of culture. Proliferative inhibition is associated with morphological changes, e.g. cell elongation and neurite prolongation, and increased activity of a marker enzyme corresponding to differentiation of OLG and with a reduced activity of the marker enzyme for AST. CONCLUSIONS: Our data suggests CUR acts continuously over a period of time, with low doses being as effective as higher doses given a longer period of treatment. It has been suggested that CUR’s anti-inflammatory and anti-oxidant actions may be useful in the prevention-treatment of neurodegenerative diseases, e.g. Alzheimer’s and Parkinson’s Diseases. Given neuroglial involvement in these diseases, and CUR’s observed actions on neuroglia, the data presented here may provide further explanations of CUR’s preventative-therapeutic role in these diseases.
Neuro Endocrinol Lett. 2003 Dec;24(6):469-7