RESUMO
Lycium barbarum L. (LBL) has beneficial effects on gestational diabetes mellitus (GDM) but the related mechanism remains unclear. Polysaccharides of LBL (LBLP) are the main bioactive components of LBL. miR-33, ATP-binding cassette transporter A1 (ABCA1) and sterol regulatory element-binding transcription 1 (SREBF1) affect lipid profiles, which are associated with GDM risk. LBLP may exert protective against GDM by affecting these molecules. Four LBLP fractions: LBLP-I, LBLP-II, LBLP-III, and LBLP-IV were isolated from LBL and further purified by using DEAE-Sephadex column. The effects of purified each fraction on pancreatic beta cells were comparatively evaluated. A total of 158 GDM patients were recruited and randomly divided into LBL group (LG) and placebo group (CG). miR-33 levels, lipid profiles, insulin resistance and secretory functions were measured. The association between serum miR-33 levels and lipid profiles were evaluated by using Spearman's rank-order correlation test. After 4-week therapy, LBL reduced miR-33 level, insulin resistance and increased insulin secretion of GDM patients. LBL increased the levels of ABCA1, high-density lipoprotein cholesterol (HDL-C) and reduced miR-33, SREBF1, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), and malondialdehyde. Homeostatic model assessment of ß-cell function and insulin resistance was lower in LG than in CG, whereas homeostatic model assessment of ß-cell function and insulin secretory function was higher in LG than in CG. There was a strong positive association between miR-33 level and TG, or TC and or LDL-C, and a strong negative association between miR-33 level and HDL-C. The levels of miR-33 had negative relation with ABCA1 and positive relation with SREBF1. ABCA1 has negative relation with TG, TC, and LDL-C and positive relation with HDL-C. Inversely, SREBF1 had positive relation with TG, TC, and LDL-C and negative relation with HDL-C. The main bioactive compound LBLP-IV of LBL increased insulin secretion of beta cells and the levels of ABCA1, and reduced miR-33 levels and SREBF1 in beta cells. However, LBLP-IV could not change the levels of these molecules anymore when miR-33 was overexpressed or silenced. LBLP-IV had the similar effects with LBL on beta cells while other components had no such effects. Thus, LBLP-IV from LBL improves lipid profiles by upregulating ABCA1 and downregulating SREBF1 via miR-33.
RESUMO
BACKGROUND Epithelial ovarian cancer is a major cause of mortality in women and one of the most common gynecologic disorders. Pterostilbene (PTS), a trans-3,5-dimethoxy-4'-hydroxystilbene, was chosen for this work due to its reported effectiveness as a chemotherapeutic agent in cancer studies. In this work, we studied underlying molecular mechanisms of PTS treatment in various ovarian cancer cell lines such as OVCAR8, OV1063, IGROV-1, and SKOV3. MATERIAL AND METHODS We used the cytometric bead array (CBA) method and real-time PCR analysis to analyze the secretion level of tumor necrosis factor alpha (TNF-α) and to measure the TNF-α mRNA expression. NF-kappa B (NF-κB) promoter analysis, Western blot analysis, electrophoresis mobility shift assay (EMSA), and immunostaining analyses were performed to measure the NF-κB activity and other relative proteins levels. RESULTS The PTS treatment decreased the release of TNF-α in IGROV-1 ovarian cancer cells. It also showed significant inhibitory effect on nuclear NF-κB p50, and NF-κB p65 protein levels. CONCLUSIONS From the results obtained, we suggest that PTS has the potential to treat ovarian cancer by reducing the level of TNF-α cytokine and to have a limited effect on NF-κB, AKT, and ERK signaling pathways.
