Abstract. Atherosclerosis is a complex inflammatory arterial disease. Oxidized low-density lipoprotein (ox-LDL) is directly associated with chronic vascular inflammation. In the current study, we tested the hypothesis that ginkgolide B, a component of traditional Chinese herbal medicine for heart disorder, may affect ox-LDL-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs). The results showed that the ox-LDL treatment caused a significantly increase in the expression of intercellular adhesion molecule-1 (ICAM-1) in HUVECs, which was associated with a dramatic augmentation in phosphorylation of IκB and relocation of nuclear factor-κB (NF-κB) into the nuclei. Interestingly, the ox-LDL-induced ICAM-1 expression and NF-κB relocation could be attenuated by addition of ginkgolide B. Moreover, ginkgolide B significantly reduces ox-LDL-induced generation of reactive oxygen species (ROS). In conclusion, ginkgolide B may decrease inflammatory responses induced by ox-LDL via blocking NF-κB signaling and inhibiting ROS generation in HUVECs.

Functional electrical stimulation can improve motor function after stroke. The mechanism may involve activity-dependent plasticity and brain remodeling. The aim of our study was to investigate the effectiveness of a patterned electrical stimulation FES mimic to gait in motor recovery among stroke survivors and to investigate possible mechanisms through brain fMRI. Forty-eight subjects were recruited and randomly assigned to a four-channel FES group (n = 18), a placebo group (n = 15), or a dual-channel FES group (n = 15). Stimulation lasted for 30 minutes in each session for 3 weeks. All of the subjects were assessed at baseline and after weeks 1, 2, and 3. The assessments included the Fugl-Meyer Assessment, the Postural Assessment Scale for Stroke Patients, Brunel's Balance Assessment, the Berg Balance Scale, and the modified Barthel Index. Brain fMRI were acquired before and after the intervention. All of the motor assessment scores significantly increased week by week in all the three groups. The four-channel group showed significantly better improvement than the dual-channel group and placebo groups. fMRI showed that fractional anisotropy was significantly increased in both the four-channel and dual-channel groups compared with the placebo group and fiber bundles had increased significantly on the ipsilateral side, but not on the contralateral side in the group given four-channel stimulation. In conclusion, when four-channel FES induces cycling movement of the lower extremities based on a gait pattern, it may be more effective in promoting motor recovery and induce more plastic changes and brain remodeling than two-channel stimulation. This trial is registered with clinical trial registration unique identifier ChiCTR-TRC-11001615.

Ginkgolide B is a herbal constituent extracted from leaves of the ginkgo biloba tree. Previous studies have shown that ginkgolide B is a specific platelet activating factor (PAF) receptor antagonist, and it suppresses PAF-mediated platelet activation via competitive binding. In this study, the effect of ginkgolide B on nicotinamide adenine dinucleotide phosphate oxidase and other inflammatory proteins in ox-LDL (low-density lipoprotein)-stimulated human vascular endothelial cells was investigated. Another PAF receptor antagonist CV3988 was employed to compare with ginkgolide B in this study. Our results show that the enhancement of Nox4 expression and reactive oxygen species generation was attenuated by ginkgolide B in cells treated with ox-LDL but not with CV3988. Increases in monocyte chemoattractant protein-1 and intercellular adhesion molecule 1 expression induced by ox-LDL, however, were inhibited by both ginkgolide B and CV3988. The translocation of NF-kappaB p65 (NF-κB) into the nucleus was inhibited by both ginkgolide B and CV3988. In conclusion, both ginkgolide B and CV3988 can inhibit the expression of inflammatory proteins by blocking NF-κB translocation. It seems that ginkgolide B possesses some pharmacological action on intracellular oxidative stress in association with the downregulation of Nox4 expression.

Aspirin has antithrombotic activity and is commonly used to protect patients from cardiovascular disease attacks. The present study investigated whether aspirin reduces reactive oxygen species and proinflammatory proteins in oxidized low-density lipoprotein (ox-LDL)-stimulated human umbilical vein endothelial cells. The results showed that aspirin attenuated reactive oxygen species generation induced by ox-LDL and downregulated Nox4 and inducible nitric oxide synthase expression. Redox-sensitive transcription factor nuclear factor kappa B was inactivated by aspirin, significantly preventing nuclear factor kappa B p65 subunit translocation into the nucleus. The expression of the monocyte/macrophage chemotactic protein 1 also decreased, but endothelial nitric oxide synthase expression increased in aspirin-treated cells. Aspirin ameliorated oxidative stress by downregulating Nox4 and inducible nitric oxide synthase and improved endothelial cell function by increasing endothelial nitric oxide synthase expression. Thus, aspirin may possess protective effects against ox-LDL-induced endothelial cell injury.