Portulaca oleracea Ameliorates Diabetic Vascular Inflammation and Endothelial Dysfunction in db/db Mice

Abstract

Type 2 diabetes is associated with significantly accelerated rates of micro- and macrovascular complications such as diabetic vascular inflammation and endothelial dysfunction. In the present study, we investigated the protective effect of the aqueous extract of Portulaca oleracea L. (AP), an edible plant used as a folk medicine, on diabetic vascular complications. The db/db mice were treated with AP (300 mg/kg/day, p.o.) for 10 weeks, and AP treatment markedly lowered blood glucose, plasma triglyceride, plasma level of LDL-cholesterol, and systolic blood pressure in diabetic db/db mice. Furthermore, AP significantly increased plasma level of HDL-cholesterol and insulin level. The impairment of ACh- and SNP-induced vascular relaxation of aortic rings were ameliorated by AP treatment in diabetic db/db mice. This study also showed that overexpression of VCAM-1, ICAM-1, E-selectin, MMP-2, and ET-1 were observed in aortic tissues of untreated db/db mice, which were significantly suppressed by treatment with AP. We also found that the insulin immunoreactivity of the pancreatic islets remarkably increased in AP treated db/db mice compared with untreated db/db mice. Taken together, AP suppresses hyperglycemia and diabetic vascular inflammation, and prevents the development of diabetic endothelial dysfunction for the development of diabetes and its vascular complications.

Figure 1

Effect of AP on weekly blood glucose levels in db/db mice. Values are expressed as mean ± SE (n = 10); **P < 0.01 versus WT; ^# P < 0.05, ^## P < 0.01 versus db/db control.

Figure 2

Effect of AP on weekly systolic blood pressure levels in db/db mice. Values are expressed as mean ± SE (n = 10); *P < 0.05, **P < 0.01 versus WT; ^## P < 0.01 versus db/db control.

Figure 3

Effect of AP on the ACh-induced (a) and SNP-induced (b) relaxation of thoracic aorta from db/db mice. Values are expressed as mean ± SE (n = 5); *P < 0.05, **P < 0.01 versus WT; ^# P < 0.05, ^## P < 0.01 versus db/db control.

Figure 4

Effect of AP on HDL cholesterol (a), triglyceride (b), and LDL cholesterol (c) levels of plasma in db/db mice. Values are expressed as mean ± SE (n = 5); *P < 0.05, **P < 0.01 versus WT; ^# P < 0.05, ^## P < 0.01 versus db/db control.

Figure 5

Effect of AP on ICAM-1 (a), VCAM-1 (b), E-selectin (c), and MMP-2 (d) expression in the aorta of db/db mice. Western blots and corresponding densitometric analyses of ICAM-1, VCAM-1, E-selectin, and MMP-2 in aortic tissue. Values are expressed as mean ± SE (n = 3); **P < 0.01 versus WT; ^## P < 0.01 versus db/db control.

Figure 6

Effect of AP on VCAM-1 and ET-1 immunoreactivity in the aorta of db/db mice. (A) Immunohistochemical staining of VCAM-1 or ET-1 in aorta from (a, e) WT, (b, f) untreated db/db mice, (e, g) db/db mice treated with rosiglitazone (10 mg/kg/day), and (d, h) db/db mice treated with AP (300 mg/kg/day). Lower panels show quantitative analysis of VCAM-1- (B) and ET-1- (C) -positive area. The average score of 5–10 randomly selected sites per section of aorta was calculated. Data expressed as mean ± SE; **P < 0.01 versus WT; ^## P < 0.01 versus db/db control. Original magnification:1000x.

Figure 7

Immunofluorescence staining of insulin in the pancreas. Representative histological sections of pancreatic islets of (a) WT, (b) untreated db/db mice, (c) db/db mice treated with rosiglitazone (10 mg/kg/day), and (d) db/db mice treated with AP (300 mg/kg/day) incubated with anti-insulin antibodies. (B) Quantitative analysis of insulin-positive area. Data expressed as mean ± SE (n = 5); **P < 0.01 versus WT; ^## P < 0.01 versus db/db control. Original magnification:1000x.