Antihyperglycemic and hypolipidemic effects of α, β-amyrin, a triterpenoid mixture from Protium heptaphyllum in mice

Abstract

Background: Pentacyclic triterpenes in general exert beneficial effects in metabolic disorders. This study investigated the effects of α, β-amyrin, a pentacyclic triterpene mixture from the resin of Protium heptaphyllum on blood sugar level and lipid profile in normal and streptozotocin (STZ)-induced diabetic mice, and in mice fed on a high-fat diet (HFD).

Findings: Mice treated with α, β-amyrin (10, 30 and 100 mg/kg, p.o.) or glibenclamide (10 mg/kg, p.o.) had significantly reduced STZ-induced increases in blood glucose (BG), total cholesterol (TC) and serum triglycerides (TGs). Unlike glibenclamide that showed significant reductions in BG, TC and TGs in normoglycemic mice, α, β-amyrin did not lower normal blood sugar levels but at 100 mg/kg, manifested a hypolipidemic effect. Also, α, β-amyrin effectively reduced the elevated plasma glucose levels during the oral glucose tolerance test. Moreover, the plasma insulin level and histopathological analysis of pancreas revealed the beneficial effect of α, β-amyrin in the preservation of beta cell integrity. In mice treated orally with α, β-amyrin (10, 30 and 100 mg/kg) or fenofibrate (200 mg/kg), the HFD-associated rise in serum TC and TGs were significantly less. The hypocholesterolemic effect of α, β-amyrin appeared more prominent at 100 mg/kg with significant decreases in VLDL and LDL cholesterol and an elevation of HDL cholesterol. Besides, the atherogenic index was significantly reduced by α, β-amyrin.

Conclusions: These findings reflect the potential antihyperglycemic and hypolipidemic effects of α, β-amyrin mixture and suggest that it could be a lead compound for drug development effective in diabetes and atherosclerosis.

Figure 1

Chemical structures of α- amyrin (A) and β- amyrin (B).

Figure 2

Treatment effects of α, β-amyrin or glibenclamide on blood glucose levels and insulin levels in streptozotocin (STZ)-induced diabetic mice. Each bar represents the mean ± SEM (n = 8) of blood glucose (mg/dL) at time 3 h and 5 h (A) or insulin at time 5 h (B). ^a p < 0.05 compared with normal control. ^b p < 0.05 compared with vehicle control.

Figure 3

Histology of mouse pancreas stained by Hematoxylin & Eosin. Normal islets of Langerhans (L) surrounded by exocrine portion (E) of pancreatic tissues in control mice (A). Destruction and distortion of endocrine cells in STZ-diabetic mice with the presence of necrotic cells and inflammatory cells (arrowhead) (B). C: Improvement in morphology of islets of Langerhans with α, β-amyrin (100 mg/kg) pretreatment in STZ-diabetic mice; D: Islets of Langerhans of diabetic mice treated with glibenclamide (10 mg/kg) showing restoration of normal cellular population. (H & E 400×), Bar: 20 μm.

Figure 4

Treatment effects of α, β-amyrin and glibenclamide in oral glucose tolerance test. Each bar represents the mean ± SEM (n = 8). ^a p < 0.05 compared with normal control. ^bp < 0.05 compared with vehicle control.