Ginkgolide A reduces inflammatory response in high-glucose-stimulated human umbilical vein endothelial cells through STAT3-mediated pathway.

Abstract

High-glucose-induced low-grade inflammation has been regarded as a key event in the onset and progression of endothelial dysfunction in diabetic vascular complications. Ginkgolide A (GA), a major compound from Ginkgo biloba extract, is widely used for the treatment of cardiovascular diseases and diabetic vascular complications. Here, its effect on high-glucose-stimulated vascular inflammation in human umbilical vein endothelial cells (HUVECs) was investigated. In the present study, the optimal stimulation conditions for HUVECs were screened for inducing endothelial inflammation, namely, high glucose at the concentration of 30mM for continuous 8h. The endothelial production of high-glucose-induced interleukin (IL)-4, IL-6, IL-13 and signal transducer and activator of transcription-3 (STAT-3) phosphorylation were significantly inhibited by the pretreatment with GA at concentrations of 10, 15 and 20μM based on enzyme-linked immunosorbent assay (ELISA), western blot or/and RT-PCR experiments. These senescent alterations induced by high glucose were significantly attenuated by the specific STAT3 inhibitor S3I-201 at the concentration of 20μM. Furthermore, the phosphorylation of STAT3, IL-4, IL-6, IL-13 and intercellular cell adhesion molecule-1 (ICAM-1) protein as well as mRNA levels were attenuated by the pretreatment of cells with STAT3 siRNA. Our results demonstrated that GA improved high-glucose-caused low-grade vascular inflammation, which might be achieved through regulating the STAT3-mediated pathway. These findings indicated that GA might be a promising candidate for attenuating vascular inflammation in diabetic vascular complications.

• Authors: Qiuping Zhao, Chuanyu Gao, Zhifeng Cui
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 25 Issue 2 Pg. 242-8 (Apr 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25681539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Ginkgolides
• IL13 protein, human
• IL4 protein, human
• IL6 protein, human
• Interleukin-13
• Interleukin-6
• Lactones
• RNA, Small Interfering
• STAT3 Transcription Factor
• STAT3 protein, human
• Intercellular Adhesion Molecule-1
• Interleukin-4
• Glucose
• ginkgolide A

Topics

• Anti-Inflammatory Agents (pharmacology)
• Cell Survival (drug effects)
• Cells, Cultured
• Ginkgolides (pharmacology)
• Glucose (metabolism)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Interleukin-13 (genetics, metabolism)
• Interleukin-4 (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Lactones (pharmacology)
• RNA, Small Interfering (genetics)
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction (drug effects)