ABSTRACT
Curcumin has been reported to have the potential to prevent obesity as well as cancers. The downstream targets regulated by AMP-activated protein kinase (AMPK) for inhibiting adipocyte differentiation or cancer cell proliferation of curcumin were investigated. The activation of AMPK by curcumin was crucial for the inhibition of differentiation or growth in both adipocytes and cancer cells. Stimulation of AMPK by curcumin resulted in the down-regulation of PPAR (peroxisome proliferator-activated receptor)-gamma in 3T3-L1 adipocytes and the decrease in COX-2 in MCF-7 cells. Application of a synthetic AMPK activator also supported the evidence that AMPK acts as an upstream signal of PPAR-gamma in 3T3-L1 adipocytes. In cancer cells, AMPK was found to act as a regulator of ERK1/2, p38, and COX-2. Regulation of AMPK and its downstream targets such as PPAR-gamma, Mapkinases, and COX-2 by curcumin appears to be important in controlling adipocytes and cancerous cells.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Cell Differentiation/drug effects , Curcumin/pharmacology , Cyclooxygenase 2/metabolism , PPAR gamma/antagonists & inhibitors , 3T3-L1 Cells , Adipocytes/cytology , Adipocytes/drug effects , Animals , Apoptosis/drug effects , Breast Neoplasms , Cell Division/drug effects , Cell Line, Tumor , Enzyme Activation/drug effects , HT29 Cells , Humans , Mice , PPAR gamma/physiologyABSTRACT
To examine the effect of two types of resistant starch on blood glucose and insulin levels, colonic events, hypolipidemic actions and humoral immune responses, Sprague-Dawley streptozotocin-induced diabetic rats were fed diet containing resistant starch from corn or rice. The marked body weight loss by inducing diabetes was not recovered by feeding resistant starch, even though there are no differences in food intakes compared to the non-diabetic control rats. No significant effect of resistant starch feeding on blood glucose and insulin was found. Even though the length of small intestines, and cecum, colon and rectum together with the tissue weight of cecum were not affected by feeding resistant starch, the intestinal transit time was markedly shortened by both types of resistant starch and resistant starch from corn had a more pronounced effect. The short chain fatty acids in the intestinal contents did not appear to be different among the groups. Nonetheless, both of resistant starch from corn and rice significantly lowered plasma total lipid and cholesterol concentrations compared to the diabetic control. The total liver cholesterol lowering effect was observed with resistant starch from rice. Neither immunoglobulin G nor C(3) were influenced by resistant starch.
Subject(s)
Blood Glucose/metabolism , Colon/metabolism , Diabetes Mellitus, Experimental/metabolism , Oryza/chemistry , Starch/pharmacology , Zea mays/chemistry , Adipose Tissue/anatomy & histology , Animals , Cecum/pathology , Colon/chemistry , Colon/pathology , Complement C3/analysis , Diabetes Mellitus, Experimental/pathology , Diet , Eating , Epididymis , Fatty Acids/analysis , Gastrointestinal Transit , Immunoglobulin G/blood , Insulin/blood , Intestinal Absorption , Lipids/analysis , Lipids/blood , Liver/chemistry , Male , Organ Size , Rats , Rats, Sprague-Dawley , Rectum/pathology , Starch/pharmacokinetics , Weight LossABSTRACT
The changes in amino acid concentrations and transsulfuration enzyme activities in liver were investigated after 4-week fed on 23% casein diet (control group) and 5% casein diet without (protein-calorie malnutrition, PCM group) or with (PCMC group) oral administration of cysteine, 250 mg/kg (twice daily, starting from the fourth week) using rats as an animal model. By supplementation with cysteine in PCM rats (PCMC group), cysteine level was elevated almost close to the control level, and glutathione (GSH), aspartic acid and serine levels were restored greater than the control levels. The measurement of transsulfuration enzyme activities exhibited that gamma-glutamylcysteine ligase (gamma-GCL) activity was up-regulated in rats with protein restriction (PCM group), and cysteine supplementation (PCMC group) down-regulated to the control level. One-week supplementation of cysteine (PCMC group) significantly down-regulated the cysteine sulfinate decarboxylase activity. These results indicate that the availability of sulfur amino acid(s) especially cysteine appears to play a role in determining the flux of cysteine between cysteine catabolism and GSH synthesis.