Quercetin potentiates transdifferentiation of bone marrow mesenchymal stem cells into the beta cells in vitro.

PURPOSE: Type 1 diabetes is an autoimmune disease caused by the destruction of ß-cells in the pancreas. Bone marrow mesenchymal stem cells are multipotent and easy accessible adult stem cells that may provide options in the treatment of type 1 diabetes. Injured pancreatic extract can promote the differentiation of rat bone marrow mesenchymal stem cells into ß-cells. We aimed to observe the effect of quercetin in differentiation and insulin secretion in ß-cells. METHODS: Bone marrow mesenchymal stem cells were obtained from the tibiae of rats. Cell surface markers were analyzed by flow cytometry. The cells were treated with rat injured pancreatic extract and quercetin for 2 weeks. Insulin secretion was measured by ELISA. Insulin expression and some islet factors were evaluated by RT-PCR. PDX1, a marker for ß-cell function and differentiation, was evaluated by both immunocytochemistry and Western blot. ß-cell count was determined by stereology and cell count assay. RESULTS: ELISA showed significant differences in insulin secretion in the cells treated with RIPE + 20 µM quercetin (0.55 ± 0.01 µg/L) compared with the cells treated with RIPE alone (0.48 ± 0.01 µg/L) (P = 0.026). RT-PCR results confirmed insulin expression in both groups. PDX1 protein was detected in both groups by Western blot and immunocytochemistry. Stereology results showed a significant increase in ß-cell number in the RIPE + quercetin-treated cells (47 ± 2.0) when compared with RIPE treatment alone (44 ± 2.5) (P = 0.015). CONCLUSIONS: Quercetin has a strengthening effect on the differentiation of rat bone marrow mesenchymal stem cells into ß-cells and increases insulin secretion from the differentiated ß-cells in vitro.

Composition and Anti-Toxicity Effects of Cichorium intybus Distillate on Serum Antioxidant Status in Carbon Tetrachloride-Treated Rats.

The role of oxidative stress in female fertility is a compelling area for research. According to traditional medicine, Cichorium intybus, known as Kasni, is believed to improve fertility. For this purpose, the effects of C. intybus distillate (CI) on blood antioxidant status were assessed in rats with carbon tetrachloride (CCl4)-induced toxicity. The rats were assigned to four experimental groups of Control, CI, CCl4, and CI+CCl410 (n=10 in each group). The level of antioxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT), as well as lipid peroxidation and reduced glutathione (GSH) level, were measured in serum samples. In the second part of the study, the antioxidant activity and phytochemical composition of the hydrodistillate of C. intybus aerial parts were determined by DPPH radical scavenging and gas chromatography-mass spectrometry analysis, respectively. The administration of CCl4 decreased the enzyme activities of GPx, GR, and CAT which were significantly ameliorated after CI administration. The decreased level of serum GSH following CCl4 administration was not considerably elevated in the CI+CCl4 group. Furthermore, the level of malondialdehyde in the serum of CI+CCl4 rats was decreased, compared to the CCl4 group. The main compositions of the essential oil from the C. intybus distillate were the antioxidants of Pulegone (8.10%), Piperitenone (7.68%), dihydroactinidiolide (5.0%), and carvone (4.18%). The antioxidant activity of the distillate was obtained at 75µg/l using the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) test. In general, the results of the present study demonstrated that C. intybus distillate, as a safe herbal remedy, can attenuate CCl4-induced oxidative damages via boosting the endogenous antioxidant defense system.

Effects of intracerebroventricular injection of glucagon like peptide-1 and its related peptides on serotonin metabolism and on levels of amino acids in the rat hypothalamus.

High concentrations of glucagon-like peptide-1 (7-36) amide (GLP-1) and its specific receptor (GLP-1R) have been found in the rat hypothalamus. In this study the actions of GLP-1 and its related peptides, exendin-4 (GLP-1R agonist), exendin (9-39) (GLP-1R antagonist) and GLP-1 (9-36) amide (the major GLP-1 metabolite) on levels of serotonin (5-HT), 5-hydroxyindolacetic acid (5-HIAA) and amino acids (Glu, Asp, Gln, Gly, Tyr, Trp, GABA) in the hypothalamus were investigated. Intracerebroventricular (ICV) injection of GLP-1 (4 nmol) produced a significant reduction in levels of 5-HT (54%) and all measured amino acids (34 to 56%) compared with saline injected controls, whereas exendin (9-39) (4 nmol) was ineffective. ICV injection of exendin-4 produced a significant reduction in the levels of 5-HT, 5-HIAA, Trp, Glu, and Tyr. ICV injection of GLP-1(9-36) amide showed a statistically significant increase in the level of 5-HT, 5-HIAA and all the amino acids tested in this study. Prior administration of exendin (9-39) or GLP-1 (9-36) amide blocked the effects of GLP-1 on the levels of 5-HT and the amino acids. These data are consistent with exendin-4 being a GLP-1R agonist and exendin (9-39) being a specific GLP-1R antagonist. GLP-1 (9-36) amide, a primary metabolite of GLP-1, appears to act as an endogenous antagonist at the GLP-1R.