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- Title
Magnesium Lithospermate B Prevents Diabetic Vascular Complication by Dual Mechanisms: Antioxidant and Aldose Reductase Inhibitor.
- Authors
Hur, Kyu Yeon; Kim, Soo Hyun; Kang, Eun Seok; Lee, Hyun Joo; Kim, So Hun; Han, Seung Jin; Chun, Sung Wan; Ahn, Chul Woo; Cha, Bong Soo; Jung, Mankil; Lee, Hyun Chul
- Abstract
Magnesium lithospermate B (LAB) is an extract of Salvia miltiorrhizae and has been known as an antioxidant. The aim of the study was to investigate the effect of LAB on the prevention of diabetic vascular complication and the mechanisms which are involved. Rat aortic vascular smooth muscle cells (VSMCs) were isolated and cultured. ROS were measured using fluorescent probe CM-H[sub 2]DCF-DA and hicigein. Aldose reductase(AR), protein kinase C (PKC), and nuclear factor (NF)-κB activity were measured. Recombinant AR and ablation of AR by small interference RNA (siRNA) were used to test the direct effect of LAB on aldose reductase activity. Hyperglycemia (FIG, 30mM, 48h)-induced VSMCs proliferation, cell cycle change, and migration were analyzed. LAB (10mg/kg/day) was injected intraperitoneally once daily to 10-weeks old male SD rats for 30 days. Neointimal hyperplasia was assessed after carotid balloon injury at 30 days by computerized morphometry. LAB (50 uM) directly inhibited both exogenous ROS and HG-induced endogenous ROS. LAB directly inhibited aldose reductase in a dose dependent manner. LAB inhibited HG-induced PKC membrane translocation and NF-κB nuclear translocation. LAB significantly inhibited VSMCs proliferation and migration in HG condition. Cell cycle analysis revealed that LAB arrested VSMCs in the G1 phase, and the percentage of cells in the S phase was similar to that of control. The neointimal hyperplasia after balloon injury in rat carotid artery was significantly reduced in LAB-treated rats compared with control (31.2% vs. 83.7%, P<0.001). These findings suggest that LAB may prevent diabetic vascular complication via direct suppression of intracellular ROS and AR. LAB may be a new therapeutic drug that can prevent diabetic vascular complications via these dual mechanisms.
- Subjects
ANTIOXIDANTS; SALVIA; VASCULAR smooth muscle; ALDOSE reductase; DIABETES complications; LABORATORY rats
- Publication
Diabetes, 2007, Vol 56, pA193
- ISSN
0012-1797
- Publication type
Article