Barbaloin Treatment Contributes to the Rebalance of Glucose and Lipid Homeostasis of Gestational Diabetes Mellitus Mice

Abstract

Aloe vera L has been shown to possess hypoglycemic and hypolipidemic effects on type 2 diabetic patients, and its major benefits may be linked to barbaloin, which is a major component of Aloe vera L. This study focused on investigating the potential effects and underlying mechanisms of barbaloin on gestational diabetes mellitus (GDM). The db/+ diabetic mice with GDM were daily orally administered with barbaloin or metformin during the gestational period. The results demonstrated that administration of barbaloin significantly reduced blood glucose levels and increased insulin levels in GDM mice. We further found that barbaloin treatment reduced inflammatory response and ROS levels in the liver. Finally, we revealed that the AMP-activated protein kinase (AMPK) / peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signaling pathway was involved in BAT-mediated beneficial effects on mice with GDM. Our study suggested that barbaloin exerted hypoglycemic and hypolipidemic effects on GDM mice, via, at least in part, modulation of AMPK/ PGC-1α signaling in GDM mice.

Keywords: barbaloin; gestational diabetes mellitus; glucose; inflammation; oxidative stress.

Figure 1.

Barbaloin reduces gestational diabetes mellitus phenotypes in pregnant mice model of GDM. (A) Chemical structure of barbaloin. Maternal body weight (B) was measured on gestation day (GD) 20 among different groups. Blood glucose (C) and serum insulin (D) were measured on gestation day (GD) 0, 10 and 20. Data are presented as mean ± SD. n = 8 for each group. **p < 0.01 compared to wild type group, ^&p < 0.05, ^&&p < 0.01 compared to GDM mice.

Figure 2.

Barbaloin ameliorated biochemical indexes in gestational diabetes mellitus mice in the late stage of pregnancy. Total serum cholesterol (TCh) (A), serum triglyceride (TG) (B), serum high-density lipoprotein (HDL) (C), serum low-density lipoprotein (LDL) (D) were tested on GD 20 among different groups. Data are presented as mean ± SD. n = 8 for each group. **p < 0.01, ***p < 0.001 compared to wild type group, ^&p < 0.05, ^&&p < 0.01 compared to GDM mice.

Figure 3.

Barbaloin decreased the inflammatory response in gestational diabetes mellitus mice. Serum IL-6 (A), TNF-α (B) and MCP-1 (C) concentrations were measured by ELISA on GD 20 among different groups. qRT-PCR was used to analyzed the mRNA levels of IL-6 (D), TNF-α (E) and MCP-1 (F) in liver tissue on GD 20 among different groups. GAPDH was set as a loading control and the relative expressions were normalized to wild type. Data are presented as mean ± SD. n = 8 for each group. **p < 0.01, ***p < 0.001 compared to wild type group, ^&p < 0.05, ^&&p < 0.01 compared to GDM mice.

Figure 4.

Barbaloin decreased the ROS levels in gestational diabetes mellitus mice. Malondialdehyde (MDA) (A), superoxide dismutase (SOD) (B), glutathione peroxidase (GPx) (C), glutathione (GSH) (D) in liver tissue were measured by ELISA on GD 20 among different groups. Data are presented as mean ± SD. n = 8 for each group. **p < 0.01, ***p < 0.001 compared to wild type group, ^&p < 0.05, ^&&p < 0.01 compared to GDM mice.

Figure 5.

Barbaloin activates hepatic AMPK pathway in gestational diabetes mellitus mice. A, the expressions of AMPKα, PGC-1αin liver tissue were measured by Western blot on GD 20. GAPDH was set as a loading control and the relative expressions were normalized to wild type (B). Data are presented as mean ± SD. n = 8 for each group. **p < 0.01, ***p < 0.001 compared to wild type group, ^&p < 0.05, ^&&p < 0.01 compared to GDM mice.