1.Hypoglycemic and antioxidant effects of jaceosidin in streptozotocin-induced diabetic mice.
Eunkyo PARK ; Byoung Mog KWON ; In Kyung JUNG ; Jung Hyun KIM
Journal of Nutrition and Health 2014;47(5):313-320
PURPOSE: In this study, we investigated the effects of jaceosidin on blood glucose regulation in type 1 diabetic mice. METHODS: C57BL/6 mice were divided into four groups; normal control (Normal), diabetes control (D-Control), diabetes low-jaceosidin (D-0.005%), and diabetes high-jaceosidin (D-0.02%). Type 1 diabetes was induced by streptozotocin and mice were then fed a diet containing jaceosidin for eight weeks. Fasting blood glucose, oral glucose tolerance test, insulin tolerance test, lipid peroxidation, and antioxidant enzyme activities were assessed. RESULTS: Jaceosidin supplementation for eight weeks had no effect on body weight, organ weight, and blood lipid profiles. However, jaceosidin supplementation significantly lowered fasting blood glucose level and reduced insulin resistance. We also found that jaceosidin supplementation increased antioxidant capacity by enhancement of catalase and GSH-px activities. CONCLUSION: These results suggest that jaceosidin could be a therapeutic candidate to ameliorate hyperglycemia through increase of antioxidant enzyme activity.
Animals
;
Antioxidants*
;
Blood Glucose
;
Body Weight
;
Catalase
;
Diabetes Mellitus
;
Diet
;
Fasting
;
Glucose Tolerance Test
;
Hyperglycemia
;
Insulin
;
Insulin Resistance
;
Lipid Peroxidation
;
Mice*
;
Organ Size
;
Streptozocin
2.Inhibition of acyl-coenzyme A:cholesterol acyltransferase stimulates cholesterol efflux from macrophages and stimulates farnesoid X receptor in hepatocytes.
Sojin AN ; Young Soon JANG ; Ji Seon PARK ; Byoung Mog KWON ; Young Ki PAIK ; Tae Sook JEONG
Experimental & Molecular Medicine 2008;40(4):407-417
We investigated the mechanism of spontaneous cholesterol efflux induced by acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibition, and how an alteration of cholesterol metabolism in macrophages impacts on that in HepG2 cells. Oleic acid anilide (OAA), a known ACAT inhibitor reduced lipid storage substantially by promotion of cholesterol catabolism and repression of cholesteryl ester accumulation without further increase of cytotoxicity in acetylated low-density lipoprotein-loaded THP-1 macrophages. Analysis of expressed mRNA and protein revealed that cholesterol 7alpha-hydroxylase (CYP7A1), oxysterol 7alpha- hydroxylase (CYP7B1), and cholesterol 27-hydroxylase (CYP27) were highly induced by ACAT inhibition. The presence of a functional cytochrome P450 pathway was confirmed by quantification of the biliary cholesterol mass in cell monolayers and extracelluar medium. Notably, massively secreted biliary cholesterol from macrophages suppressed the expression of CYP7 proteins in a farnesoid X receptor (FXR)-dependent manner in HepG2 cells. The findings reported here provide new insight into mechanisms of spontaneous cholesterol efflux, and suggest that ACAT inhibition may stimulate cholesterol-catabolic (cytochrome P450) pathway in lesion-macrophages, in contrast, suppress it in hepatocyte via FXR induced by biliary cholesterol (BC).
Anilides/*pharmacology
;
Bile/metabolism
;
Cells, Cultured
;
Cholesterol/*metabolism
;
Cholesterol Esters/metabolism
;
DNA-Binding Proteins/agonists/*metabolism
;
Enzyme Inhibitors/pharmacology
;
Gene Expression Regulation, Enzymologic/drug effects
;
Hepatocytes/*drug effects/metabolism
;
Humans
;
Lipid Metabolism/drug effects/genetics
;
Macrophages/*drug effects/metabolism
;
Models, Biological
;
Oleic Acids/*pharmacology
;
Receptors, Cytoplasmic and Nuclear/agonists/*metabolism
;
Sterol O-Acyltransferase/*antagonists & inhibitors/physiology
;
Transcription Factors/agonists/*metabolism