Browsing by Subject "curcumin"
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Item CURCUMIN SUPPLEMENTATION IMPROVES CERTAIN ASPECTS OF COGNITION AND ALLEVIATES INFLAMMATION, INDEPENDENT OF ADIPOSITY(2014-03) Sarker, Marjana R.; Franks, Susan F.; Sumien, Nathalie; Filipetto, Frank; Forster, MichaelThe study was designed to investigate the effects of curcumin on blood based biomarkers and mental health in a chronic mid-life obese state. 3 groups were studied, mice on a regular diet, on a calorically restricted diet and on a regular diet supplemented with curcumin. These mice were kept on their respective diets for 12 weeks. Two behavioral studies to investigate mental health in particular memory, were utilized. Our results conclude that curcumin dietary treatment positively affects specific domains of mental health possibly by the lowering of inflammation but this effect is independent of fat loss. Purpose (a): Midlife obesity has been recently associated with cognitive impairment that may be attributed to chronic, obesity-related inflammation and oxidative stress. Commonly used laboratory mice fed ad libitum are an analogue of weight gain in middle aged humans, since accumulating fat is more often the result of food intake exceeding energy expenditure and not solely because of a high fat diet. The current study addressed the hypothesis that curcumin supplementation, by attenuating obesity and adiposity -related inflammation, would improve cognition in a midlife obesity animal model. Methods (b): C57BL/6J male mice were maintained under ad libitum (AL) feeding until they reached peak weight at 15 months of age, as a model of inactivity-related weight gain. The mice were subsequently assigned in groups of 19 to: (i) remain on AL, (ii) receive 30% caloric restriction (CR) or (iii) receive curcumin in their AL diet (1000 mg/kg diet, CURC) for 12 weeks. Mice underwent tail bleeds for the inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP) and, after 8 weeks of dietary treatment, spatial cognitive function was tested using a Morris water maze, followed by testing for cognitive flexibility using a discriminated avoidance, serial reversal task. Visceral (VAT) and subcutaneous (SAT) adipose tissue was collected after 12 weeks of the treatments. Results (c): Mice maintained on CR weighed significantly less than mice on the CURC and AL diets by the third week of treatment. Food intake of the CURC group was significantly higher than AL. Mice on CR and CURC diets took fewer trials than AL to reach criterion during the second reversal session of discriminated avoidance, suggesting that both conditions improved cognitive flexibility. However, there were no significant differences between the groups in their spatial cognitive performance. Mice maintained on CR had significantly less VAT and SAT compared to mice on CURC and AL. Curcumin supplementation did not significantly impact IL-6 levels but it did reduce CRP relative to AL mice. Conclusions (d): Results suggest that in a midlife obesity animal model, curcumin supplementation has positive effects on frontal cortical functions that may be linked to an anti-inflammatory action. It appears that these effects may be independent of adiposity. Curcumin intake may also facilitate energy expenditure or diminish efficiency, as suggested by the increase in energy intake in the absence of weight loss in the CURC mice. Future studies will determine the metabolic and cognitive consequences of higher curcumin doses.Item Dietary Curcumin And Caloric Restriction As Interventions For The Reversal Of Age Associated Functional Decline(2015-12-01) Sarker, Marjana R.; Forster, Michael J.; Franks, Susan; Sumien, NathalieAugmentation and exacerbation of oxidative stress and low-grade chronic systemic inflammation during mid-life has been proposed as modifiable causative factors for neurobehavioral decline reported with normal aging. Physiologically, the imbalance of pro-oxidants and endogenous antioxidants leads to an increase in tissue- damaging oxidative stress. Aging has also been associated with chronic systemic inflammation that can damage healthy tissues and diminish cognitive and motor capacity. The overall hypothesis of this project is that caloric restriction and dietary curcumin, via their strong anti-oxidant and anti-inflammatory properties; can delay the onset or ameliorate cognitive and motor decline in middle aged and aged mice respectively. Study 1: Fifteen month-old male C57BL/6 mice were tested as a model of sedentary mid-life obesity for the pilot study. They underwent dietary treatment for 12 weeks and were subjected to cognitive tests at the 8th week of treatment. Dietary treatments included regular chow fed ad libitum (AL), curcumin (1g/kg of diet) fed ad libitum (CURAL) and 30% to weight stable caloric restriction (CR). Mice were tested for spatial learning and cognitive flexibility testing. Blood was collected to measure inflammation and oxidative stress. Results from the pilot study indicated a significant weight loss and reduced adiposity in the CR group; whereas CURAL mice maintained stable weight throughout the treatment, consumed more food than the AL mice, and did not show a reduction of adipose tissue. However, both the CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and reduced glutathione as well as the GSH/GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. Study 2: In the subsequent study, 15 and 20 month old female and male C57BL/6 mice were used as a normal aging model to study functional decline. This study included all of the dietary interventions from the pilot study and an additional combination diet of CR and curcumin (CURCR). Curcumin was added to the diet at 7g/kg of diet with mice under CURCR receiving 7.2g/kg of diet, adjusted to take difference in food intake into account. The mice underwent dietary treatments for 4 months, and cognitive and motor behavior tests were conducted at 8 weeks of treatment. Mice were tested on multiple tasks that are sensitive to age associated cognitive and motor dysfunction. Results from the second study indicated females to be more active than males. Mice under CR and CURCR performed better in the motor tests compared to their age matched controls, which included coordinated running, wire suspension and bridge walking. Cognitive flexibility was significantly better for middle-aged males under CR and CURAL compared to AL but not under CURCR, suggesting an antagonistic interaction. On the other hand, middle aged and aged female experimental groups did significantly better than AL. No interaction of CR and CUR was observed in aged males, with CURAL and CR yielding comparable benefits. None of the treatments had a significant effect on hippocampus- dependent rate of learning in middle age or the aged; however middle aged males under the CURCR intervention had poorer probe performance compared to their age matched controls. Data from both projects suggest that independent of weight loss; dietary curcumin and CR have positive effects on fronto-cortical functions in late middle age and senescence that could be linked to anti-inflammatory or antioxidant actions. These effects were similar across different behavioral tasks and were non-additive or antagonistic in a sex dependent manner, suggesting that they could involve the same or similar mechanisms including an influence of sex hormones. Therefore, curcumin intake may mimic the neurobehavioral outcomes of CR that could be age dependent, but the mechanism of action underlying the outcomes of the CR and curcumin combination treatments need to be further examined.Item PREPARATION AND CHARACTERIZATION OF NOVEL MULTIFUNCTIONAL LIPOPOLYMERIC HYBRID NANOSYSTEMS FOR IMAGING AND THERAPY OF HIGHLY METASTATIC BREAST CANCER(2013-04-12) Mukerjee, AninditaPurpose: The technology based design of nanosystems has become more complex over the years since it now combines multiple functionalities within nanoparticles as a single delivery system. One such design involves combining the advantages of biodegradable polymeric nanoparticles with the biomimetic properties of liposomes. In this study, we have successfully engineered a multifunctional lipopolymeric hybrid nanosystem encapsulating an anticancer agent, curcumin, with a fluorescently labeled dye for imaging and therapy of breast cancer. Methods: Functionalized curcumin loaded hybrid nanoparticles for was prepared by nanoprecipitation method. The hybrid nanoparticles thus formulated were then characterized for drug loading, particle size, zeta potential and surface morphology. To evaluate our nanosystems, intracellular uptake of these drug loaded nanosystems along with its effect on cellular migration in non-malignant (MCF10A) and highly malignant metastatic breast cancer cell lines (MCF10CA1a) was determined. Further, functional assays like cell viability assay were carried out to determine the functional integrity of the encapsulated drug. Long-term stability analysis of the hybrid nanoparticles were carried out for 6 days at room temperature. Results: The formulation of the lipopolymeric hybrid nanosystem by nanoprecipitation was found to be successful with a drug loading of 12.4 ± 0.8 µg/mg of nanoparticles for curcumin. The particle size distribution was narrow with the mean particle size being 116.8 ±10 nm. The zeta potential of these hybrid nanoparticles was determined to be -31.66mV.The surface morphology of the hybrid nanoparticles was determined by Transmission Electron Microscopy. Results revealed smooth and spherical nanoparticles. Intracellular uptake studies were carried out in highly malignant breast cancer cell line, MCF10CA1a. Confocal Microscopy scans show robust cellular uptake of the fluorescently labeled hybrid nanosystems. Long-term stability analysis results reveal that these hybrid nanoparticles are stable in PBS for as long as 6 days with only ±5 nm change observed in mean particle size. Conclusions: We successfully formulated the lipopolymeric hybrid nanosystem with a fluorescently labeled dye and an anticancer agent. This type of a combinatorial theranostic system platform would allow for imaging and therapy with much less side effects than the traditional treatments because it will use anticancer agents at lower doses than used in current chemotherapies.