RETRACTED: Polysaccharide IV from Lycium barbarum L. Improves Lipid Profiles of Gestational Diabetes Mellitus of Pregnancy by Upregulating ABCA1 and Downregulating Sterol Regulatory Element-Binding Transcription 1 via miR-33

Abstract

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 β-cell function and insulin resistance was lower in LG than in CG, whereas homeostatic model assessment of β-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.

Bioactive Components of Lycium barbarum and Deep-Processing Fermentation Products

“…It also rose the high-density lipoprotein cholesterol and reduced the blood ester and malondialdehyde. LBLP IV had significant anti-diabetic activity on gestational diabetes mellitus [27]. The composition and function of LBPs are shown in Table 1.…”

Supercharging metabolic health with Lycium barbarum L.: A review of the therapeutic potential of this functional food for managing metabolic syndrome

“…Interestingly, a significant decrease in the level of TNF‐α was detected in the L. barbarum treated group, but not in other adipokines, including adiponectin, leptin, and IL‐6 (Cai et al., 2015). Another study reported that the consumption of polysaccharides of L. barbarum (10 mg daily) during 4 weeks reduced insulin resistance, LDLc, total cholesterol, triglycerides, and malondialdehyde (MDA) and increased insulin release and HDLc in gestational diabetes mellitus patients (Yang et al., 2018). The mechanism of action evaluated in human pancreatic carcinoma cell SW1990 was related to an increase in ATP‐binding cassette transporter A1 and a downregulation of SREBP‐1c via miR‐33.…”

The Role of Fibroblast Growth Factor 21 in Diabetic Cardiovascular Complications and Related Epigenetic Mechanisms

“…In addition, although no directly evidence showed that miRNA-33 was involved in the treatment of DM-induced vascular dysfunction so far. Yang et al has shown that miRNA-33 acts as a key regulator in gestational DM of pregnancy ( 92 ). Thus, it is still worth for further exploration on the role of miRNA-33 in the effect of FGF21 on DM-induced atherosclerosis.…”