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Keywords. grape seed procyanidin B2, mimecan, nuclear factor-KB, mice, diabetic nephropathy
Grape seed procyanidin B2 (GSPB2) exerts a variety of potent protective pharmacological effects on diabetic complications. The renal protective effects of GSPB2 and the target protein mimecan regulated by GSPB2, discovered in a previous quantitative proteomic analysis, were assessed in mice with diabetic nephropathy Twenty-four db/db mice were divided into 2 groups of the vehicle-treated and GSPB2-treated (30 mg/kg/d) diabetic groups. All animals were observed for 10 weeks. Treatment with GSPB2 resulted in an improvement in body weight increase and serum levels of triglyceride, total cholesterol, advanced glycation end products, and urinary albumin excretion in comparison with the vehicle-treated diabetic mice (P < .05), although these levels were still higher than those in the control group. Treatment with GSPB2 significantly reduced the extent of glomerular basement membranes thickening, mesangial expansion, and glomerular area as well. Mimecan protein expressions in diabetes mellitus were decreased approximately by 28% when compared with those in the control group (P < .05), and restored remarkably after GSPB2 treatment (P < .05). The expression of nuclear factor-KB (NF-kB) p65 in nuclear extracts, markedly higher in the diabetic mice than in the controls, was significantly suppressed by GSPB2. The findings of this study revealed that mimecan might become a new therapeutic target in the future and indicated that GSPB2 had beneficial effects not only on oxidative stress, but also on renal fibrosis, particularly in the diabetic kidney.
IJKD 2016;10:325-31
www.ijkd.org
Diabetic nephropathy (DN) occurs in about 35% of diabetic patients and is becoming a major health problem worldwide.1-3 Numerous studies have pointed to the role of long-term hyperglycemia-induced oxidative stress in the development of DN.4,5 Therefore, alleviating oxidative stress may be a novel prospective approach for DN.6 Our previous studies demonstrated that grape seed proanthocyanidin extract exerts a variety of potent protective pharmacological effects on diabetic complications, especially on diabetic kidney,7-9 attributed to antioxidant, anti-inflammatory, anti-atherosclerosis, and free-radical scavenging effects.10,11 Grape seed procyanidin B2 (GSPB2) is one of the main dimeric forms, which has higher biological activities than other water-soluble polyphenos. We investigated the protective effects of GSPB2, on renal complications of mice.
In our team previous study,12 we resorted to a quantitative proteomic assay to get the differential...