Ginkgo biloba extract prevents glucose‐induced accumulation of ECM in rat mesangial cells

Abstract

Pathological remodeling characterized by extracellular matrix (ECM) accumulation contributes to diabetic nephropathy (DN). This study evaluated the effects of Ginkgo biloba extract (GbE) on the metabolism of the ECM in rat mesangial cells cultured in hyperglycemic conditions. The cultured mesangial cells in high glucose conditions were allotted into six groups: normal control group, high glucose group, low concentration of GbE group, moderate concentration of GbE group, high concentration of GbE group, and captopril group. In the presence of high glucose, the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and extracellular matrix metalloproteinase inducer (EMMPRIN) were decreased significantly, and the levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) were increased significantly. These changes were reversed by GbE. GbE lowered the levels of transforming growth factor-beta(1) (TGF-beta(1)), insulin-like growth factor-1 (IGF-1) and connective tissue growth factor (CTGF) of the high glucose group. Furthermore, GbE also decreased the expressions of collagen IV and laminin of the high glucose group. In summary, the results suggest that GbE postpones the extracellular matrix accumulation by inhibiting the synthesis of ECM and promoting the degradation of ECM, and therefore, is a potential drug for the prevention and treatment of DN.

Ginkgo biloba extract reduces high-glucose-induced endothelial adhesion by inhibiting the redox-dependent interleukin-6 pathways

“…There have been very few, mainly in vitro, evidence for the effects of GBE in the presence of high glucose [36]. To our knowledge, this is the first study demonstrating the direct endothelial protection effects of GBE in the presence of long-term high glucose.…”

Ginkgo biloba extract inhibits oxidized low-density lipoprotein (oxLDL)-induced matrix metalloproteinase activation by the modulation of the lectin-like oxLDL receptor 1-regulated signaling pathway in human umbilical vein endothelial cells

“…12 We previously showed that GbE mitigates oxLDLinduced oxidative injury in human endothelial cells by repressing reactive oxygen species (ROS) generation, the earliest signaling event that occurs in oxLDL-caused endothelial dysfunction. 13 Ji et al 14 reported that GbE reduces glucose-caused accumulation of MMPs in rat mesangial cells. However, the probable mechanism that GbE uses to protect against atherosclerosis development remains to be elucidated.…”

Over-production of nitric oxide by oxidative stress-induced activation of the TGF-β1/PI3K/Akt pathway in mesangial cells cultured in high glucose

“…TGF-β1, a very important growth factor in DN pathogenesis, has been reported to be up-regulated in the kidney under diabetic conditions using in vitro [20][21][22][23]25] and in vivo [6][7][8]24] studies. In the present study, both high glucose and H 2 O 2 led to npg increased TGF-β1 protein and mRNA expression in rat MCs, and these were then reduced by treatment with DPI, suggesting that ROS mediated high glucose-induced TGF-β1 production.…”

“…Data from other laboratories [20][21][22] and our team [6][7][8][23][24][25] have demonstrated www.nature.com/aps Zhai YP et al Acta Pharmacologica Sinica npg that transforming growth factor β1 (TGF-β1) is the core factor that contributes to DN pathogenesis. Most of the studies on the pathologic effects of TGF-β1 on DN simply focus on its profibrotic effect, while other potential mechanisms remain unclear.…”