2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone promoted glucose uptake and imposed a paradoxical effect on adipocyte differentiation in 3T3-L1 cells.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), one of the flavonoids isolated and purified from the dried flower buds of Cleistocalyx operculatus, was explored for its function in glucose uptake/glycogen synthesis in insulin-sensitive tissue cells and its effect and mechanism on 3T3-L1 preadipocyte differentiation. DMC (10 µM) treatment remarkably promoted glucose uptake in differentiated 3T3-L1 adipocytes (P < 0.05 vs control group), whereas the glucose uptake in L6 myoblasts and glycogen synthesis in HepG2 hepatocytes were not affected by the treatment. DMC had paradoxical effects on lipid accumulation in 3T3-L1 cells compared with differentiation control. High concentrations of DMC (10 and 20 µM) markedly diminished lipid accumulation; however, a low concentration of DMC (2.5 µM) enhanced lipid storage in 3T3-L1 cells (P < 0.01 vs differentiation control group), and 5 µM DMC did not impose a significant effect. It was demonstrated that the effect of DMC in lipid accumulation was controlled by the expression of PPAR-γ.

Protective effects of 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone against hydrogen peroxide-induced oxidative stress in hepatic L02 cell.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a chalcone isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry, and the hepatoprotective effects of DMC on Kunming mice have been studied in previous study. However, the effects of DMC on hepatocyte toxicity and corresponding mechanism remain unclear. The aim of this study was to evaluate the hepatoprotective mechanism of DMC in human hepatocytes (L02) treated with H2O2. The results demonstrated that pretreatment with DMC effectively protected H2O2-induced cell viability loss, cell membrane damage (lactate dehydrogenase, nitric oxide production and caspase-3 accumulation. Besides, DMC pretreatment increased the amount of glutathione, decreased malondialdehyde and the percentage of apoptotic L02 cells compared with only H2O2 treated group. Taken together, these results indicated that DMC had hepatoprotective effects against H2O2-induced liver injury by alleviating oxidative stress and apoptosis process in L02 cells, and DMC might be a potential candidate for the intervention of liver diseases.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone protects the impaired insulin secretion induced by glucotoxicity in pancreatic ß-cells.

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), which is isolated and purified from the dried flower buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its insulinotropic benefits against glucotoxicity using in vitro methods. When exposed to high glucose at the cytotoxicity level for 48 h, RIN-5F ß-cells experienced a significant viability loss and impaired insulin secretion function, whereas cotreating with DMC could protect ß-cells against glucotoxicity-induced decrease in glucose-stimulated insulin secretion in a dose-dependent manner without affecting basal insulin secretion. It was demonstrated that DMC increased insulin secretion against glucotoxicity by simulating the effect of GLP-1 and enhancing the expression of GLP-1R, followed by activating the signal pathway of PDX-1, PRE-INS, and GLUT2-GCK. Another mechanism was that DMC avoided the pancreatic islet dysfunction resulting from cellular damage by suppressing the production of nitric oxide (NO) by iNOS, and the expression of MCP-1. The results indicated the potential application of DMC in the intervention against glucotoxicity-induced hyperglycemia.

[The characteristics of type I, III collagen and LN in pulmonary fibrosis induced by uranium ore dust in rats].

OBJECTIVE: To explore the characteristics of LN and type I, III collagen in pulmonary fibrosis induced by uranium ore dust in rats. METHODS: 60 adult Wistar rats were divided randomly into two groups, control group (30 rats) and uranium ore dust group (30 rats). Non-exposed intratracheal instillation method was used. Uranium ore dust group was exposed 20 mg/ml uranium ore dust suspension 1ml per rat, meanwhile control group was exposed normal saline 1ml per rat. Post-exposed the 7, 14, 21, 30 and 60 d, 6 rats in each group were killed randomly, lung tissue were collected. The pathological changes in lung tissue were observed by microscope using HE staining, the collagen I and III in lungs were observed by polarizing microscope using Biebrich scarlet staining. The expression of LN protein in lung tissue was observed by immunohistochemistry-SP. RESULTS: During lung fibrosis, a large amount of the proliferated I and III collagen in lungs were observed. Post-exposure to uranium ore dust, the characteristics in proliferated collagen in lungs were type I collagen deposited in lung interstitium mainly in the early stage. The area percentage of collagen I and III was increased significantly at 7, 14, 21, 30 and 60d in the experimental group as compared with that in the control group (P < 0.05 or P < 0.01). The over expression of LN in the lung tissue were observed. The expression of LN was distributed in the lung tissue as thickening of the linear or cluster. The integral optical density of LN was increased significantly at 21, 30 and 60 d in the experimental group as compared with that in the control group (P < 0.05 or P < 0.01). CONCLUSIONS: After exposure to uranium ore dust, the characteristics in proliferated collagen in lungs are the type of I collagen deposited in lung interstitium mainly in the early stage, while the type of III collagen increase significantly at the later period. The overexpression of LN exists in the process of pulmonary fibrosis. It suggests that LN has a role effect in the process of pulmonary fibrosis.